Clinical Trial Results:
Fatigue in Sarcoidosis - A feasibility study investigating the treatment of fatigue in stable sarcoidosis patients using methylphenidate
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Summary
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EudraCT number |
2016-000342-60 |
Trial protocol |
GB |
Global end of trial date |
09 Jul 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
09 Jun 2022
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First version publication date |
09 Jun 2022
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
190280
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02643732 | ||
WHO universal trial number (UTN) |
U1111-1180-0191 | ||
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Sponsors
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Sponsor organisation name |
Norfolk and Norwich University Hospital
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Sponsor organisation address |
Colney Lane, Norwich, United Kingdom, NR4 7UY
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Public contact |
Lisa Chalkley, Norfolk and Norwich University Hospital NHS Foundation Trust, +44 01603286611, lisa.chalkley@nnuh.nhs.uk
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Scientific contact |
Lisa Chalkley, Norfolk and Norwich University Hospital NHS Foundation Trust, +44 01603286611, lisa.chalkley@nnuh.nhs.uk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
10 May 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
09 Jul 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
09 Jul 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objectives for this trial is to determine whether it is feasible to perform a suitably large randomised controlled trial investigating whether methylphenidate is a clinically effective treatment for fatigue in sarcoidosis, and how best to design this trial to successfully answer this question.
As a result, the main research questions are:
(1) What is the recruitment rate of participants/how quickly can we recruit people into the trial? (How many studies might need to be involved in a future trial?)
(2) How many patients with sarcoidosis are excluded from the study and for what reason? (as above)
(3) How many people who are included in the study manage to complete the study? (How many participants extra do we need to ensure statistical power is maintained allowing for drop-outs)
(4) Why are potential participants excluded from the study, and why do participants withdraw/drop-out of the study? (as above, as well as generalisability of the results – is the population i
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Protection of trial subjects |
Monitoring of all high risks during the trial - blood pressure, liver function, ECG. These were done at all visits through the trial where participants were potentially receiving the IMP (weeks 2,4,6,12,18 and 24).
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Background therapy |
None | ||
Evidence for comparator |
Comparator is placebo - identical gel caps containing lactose powder only (compared with gel caps including the active methylphenidate pill, then packed with lactose powder. | ||
Actual start date of recruitment |
25 Apr 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 22
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Worldwide total number of subjects |
22
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
18
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From 65 to 84 years |
4
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants were recruited from the Norfolk and Norwich University Hospital (Norwich, Norfolk, UK) with patients referred from other centres for consideration of trial inclusion. Recruitment was open between 07/11/2016 and 02/03/2018. | |||||||||
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Pre-assignment
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Screening details |
Participants were screened via medical notes (all patients with sarcoidosis under the care of the Norfolk and Norwich University Hospital against eligibility criteria; A proven diagnosis of sarcoidosis, stable disease, able to give informed consent and a Fatigue Assessment Scale score >21 points. | |||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Monitor, Carer, Assessor | |||||||||
Blinding implementation details |
Placebo and active treatments appeared identical. Trial pharmacists at NNUH were aware of the treatment group due to unequal arm size; they did not disclose the group allocation and medication labels did not reference the allocated group; this data was contained on a tear-off strip which was removed prior to dispensing to the study team. During study monitoring and auditing, pharmacy monitoring was performed by a member of staff from Norwich CRTU to maintain blinding of the study team.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Active treatment | |||||||||
Arm description |
Methylphenidate, up to 20mg BD | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Methylphenidate
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, soft + tablet
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Routes of administration |
Oral use
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Dosage and administration details |
10mg BD for 2 weeks then increased to 20mg BD to the end of the trial. Participants could opt-out of the up titration if they felt they had adequate benefit at the lower dose. Down-titration to the lower dose could occur if certain side effects occurred; following this, it was not possible to uptitrate back to the higher dose.
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Arm title
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Placebo | |||||||||
Arm description |
Placebo medication - identical capsule to the active treatment arm | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, soft
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Routes of administration |
Oral use
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Dosage and administration details |
Identical placebo to active treatment (methylphenidate) - this was a soft capsule containing lactose powder.
Started at 1 tablet BD, increased to 2 tablets BD after 2 weeks if no side effects had occurred. Participants could opt out of the dose increase if adequate clinical improvement had already occurred. Down-titration from the higher dose could occur if side effects became apparent on the higher dose; once this occurred it was not possible to uptitrate back up to the higher dose.
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Baseline characteristics reporting groups
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Reporting group title |
Active treatment
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Reporting group description |
Methylphenidate, up to 20mg BD | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Placebo medication - identical capsule to the active treatment arm | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Active treatment
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Reporting group description |
Methylphenidate, up to 20mg BD | ||
Reporting group title |
Placebo
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Reporting group description |
Placebo medication - identical capsule to the active treatment arm | ||
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End point title |
Medication adherence [1] | ||||||||||||
End point description |
Percentage of doses taken using pill counts at each visit to determine the number of doses that should have been taken, the number of pills expected to remain and the actual remaining pills. No participant took more than their expected number of doses. The overall count across the entire study period is reported.
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End point type |
Primary
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End point timeframe |
24 weeks total, though those recruited after December 2017 had a reduced follow-up period. (18 weeks if recruited between December and February 2018, 12 weeks if recruited after February 2018).
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The primary outcomes are feasibility outcomes and therefore do not relate to active vs placebo. It was pre-specified that no statistical analysis would take place on these primary feasibility outcomes and only exploratory statistical analysis would occur for the secondary clinical outcomes. |
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End point title |
Questionnaire missing data [2] [3] | ||||||
End point description |
A total of 1142 data points across 12 questionnaires. Data is for BOTH arms, not just active treatment arm. As this was a measure of feasibility it was not split by arm.
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End point type |
Primary
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End point timeframe |
8 visits across 30 weeks
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The primary outcomes are feasibility outcomes and therefore do not relate to active vs placebo. It was pre-specified that no statistical analysis would take place on these primary feasibility outcomes and only exploratory statistical analysis would occur for the secondary clinical outcomes. [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The primary outcomes are feasibility outcomes and therefore do not relate to active vs placebo. It was pre-specified that no statistical analysis would take place on these primary feasibility outcomes and only exploratory statistical analysis would occur for the secondary clinical outcomes. |
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End point title |
Adverse event rate [4] | |||||||||
End point description |
Number of adverse events in any organ system reported during the 30 week trial.
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End point type |
Primary
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End point timeframe |
30 weeks
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The primary outcomes are feasibility outcomes and therefore do not relate to active vs placebo. It was pre-specified that no statistical analysis would take place on these primary feasibility outcomes and only exploratory statistical analysis would occur for the secondary clinical outcomes. |
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End point title |
Activity monitor wear periods [5] [6] | ||||||||||||||
End point description |
Feasibility end-point; number of wear periods for the accelerometer activity devices and number of devices with valid data. ASA. FEASIBILITY END-POINT THE DATA IS REPORTED FOR BOTH ARMS AND WAS NOT SPLIT.
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End point type |
Primary
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End point timeframe |
24 weeks - three wear periods per individual (fewer for individuals randomised from December 2017 onwards).
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| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The primary outcomes are feasibility outcomes and therefore do not relate to active vs placebo. It was pre-specified that no statistical analysis would take place on these primary feasibility outcomes and only exploratory statistical analysis would occur for the secondary clinical outcomes. [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The primary outcomes are feasibility outcomes and therefore do not relate to active vs placebo. It was pre-specified that no statistical analysis would take place on these primary feasibility outcomes and only exploratory statistical analysis would occur for the secondary clinical outcomes. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Exit Questionnaire - Wished to continue study drug at end of trial [7] | |||||||||
End point description |
Participants were asked their perception of study enrolment
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End point type |
Primary
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End point timeframe |
Week 24 - Exit questionnaire
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| Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The primary outcomes are feasibility outcomes and therefore do not relate to active vs placebo. It was pre-specified that no statistical analysis would take place on these primary feasibility outcomes and only exploratory statistical analysis would occur for the secondary clinical outcomes. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Exit questionnaire - was participation in the study useful? [8] | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Week 24 - Exit questionnaire
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| Notes [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The primary outcomes are feasibility outcomes and therefore do not relate to active vs placebo. It was pre-specified that no statistical analysis would take place on these primary feasibility outcomes and only exploratory statistical analysis would occur for the secondary clinical outcomes. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Exit questionnaire - Given the chance again would you participate in the study? [9] | |||||||||
End point description |
Number of participants who would take part in the trial again if given the chance again
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End point type |
Primary
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End point timeframe |
Week 24 - Exit questionnaire
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| Notes [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The primary outcomes are feasibility outcomes and therefore do not relate to active vs placebo. It was pre-specified that no statistical analysis would take place on these primary feasibility outcomes and only exploratory statistical analysis would occur for the secondary clinical outcomes. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Exit Questionnaire - Would you recommend future trials including methylphenidate? [10] | |||||||||
End point description |
Number of participants who would recommend future trials investigating methylphenidate
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End point type |
Primary
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End point timeframe |
Week 24 - Exit questionnaire
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| Notes [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The primary outcomes are feasibility outcomes and therefore do not relate to active vs placebo. It was pre-specified that no statistical analysis would take place on these primary feasibility outcomes and only exploratory statistical analysis would occur for the secondary clinical outcomes. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Participants correctly predicting allocation (exit questionnaire) [11] | |||||||||
End point description |
Participants were asked to predict their allocation at the end of the trial
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End point type |
Primary
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End point timeframe |
Week 24 - Exit questionnaire
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| Notes [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The primary outcomes are feasibility outcomes and therefore do not relate to active vs placebo. It was pre-specified that no statistical analysis would take place on these primary feasibility outcomes and only exploratory statistical analysis would occur for the secondary clinical outcomes. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Investigator correctly predicting allocation at end of trial [12] | |||||||||
End point description |
Number of participants where the investigator correctly predicted the allocation of the participant whilst still blinded.
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End point type |
Primary
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End point timeframe |
Week 24 - Exit questionnaire
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| Notes [12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The primary outcomes are feasibility outcomes and therefore do not relate to active vs placebo. It was pre-specified that no statistical analysis would take place on these primary feasibility outcomes and only exploratory statistical analysis would occur for the secondary clinical outcomes. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Fatigue (FAS score) - 12 weeks | ||||||||||||
End point description |
Change in FAS score
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End point type |
Secondary
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End point timeframe |
Week 12
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Statistical analysis title |
Adjusted mean difference | ||||||||||||
Statistical analysis description |
Mean difference between groups, adjusted for baseline scores
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Comparison groups |
Active treatment v Placebo
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Number of subjects included in analysis |
22
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Analysis specification |
Pre-specified
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Analysis type |
superiority [13] | ||||||||||||
Method |
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Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
1.7
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-5.4 | ||||||||||||
upper limit |
8.7 | ||||||||||||
Variability estimate |
Standard deviation
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| Notes [13] - Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
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End point title |
Fatigue (FAS) - Week 24 | ||||||||||||
End point description |
FAS score at week 24
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Adjusted mean difference | ||||||||||||
Statistical analysis description |
Mean difference between arms adjusted for baseline values
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
16
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [14] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
6.2
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1.4 | ||||||||||||
upper limit |
13.7 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [14] - Mean difference between groups, adjusted for baseline scores Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
Fatigue (FAS) Week 30 | ||||||||||||
End point description |
Final data, taken 6 weeks after completing medications
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 30 (6 weeks post completion of medications)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Adjusted mean difference | ||||||||||||
Statistical analysis description |
Mean difference 0 week 30 fatigue (FAS) score
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
20
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [15] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
7
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
1.3 | ||||||||||||
upper limit |
12.8 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [15] - Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
FACIT-Fatigue Week 12 | ||||||||||||
End point description |
FACIT-Fatigue score
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Mean difference (adjusted) | ||||||||||||
Statistical analysis description |
Adjusted mean difference (for baseline FAS scores) between arms
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
22
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [16] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-0.4
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-9.1 | ||||||||||||
upper limit |
8.2 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [16] - Planned analysis at week 12 of difference between arms 1Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
FACIT-Fatigue Week 24 | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 24 (Final data point whilst receiving medication)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Adjusted between-group mean difference | ||||||||||||
Statistical analysis description |
Between-group mean difference (adjusted for baseline fatigue FAS scores)
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
16
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [17] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-9.2
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-17.8 | ||||||||||||
upper limit |
-0.6 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [17] - 1Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
FACIT-Fatigue Week 30 | ||||||||||||
End point description |
FACIT-Fatigue score at week 30 (6 weeks after ceasing medications)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 30
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Adjusted between-group difference | ||||||||||||
Statistical analysis description |
Mean difference between arms at week 30; difference adjusted for baseline fatigue (FAS) score
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
20
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [18] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-6.9
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-14.7 | ||||||||||||
upper limit |
1 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [18] - 1Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
Anxiety (HADS-A) Week 12 | ||||||||||||
End point description |
HADS-A score
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Mean group difference (adjusted) | ||||||||||||
Statistical analysis description |
Adjusted between-group difference (adjusted for baseline fatigue/FAS score)
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
22
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [19] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
2.7
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.4 | ||||||||||||
upper limit |
5 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [19] - Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
Anxiety (HADS-A) Week 24 | ||||||||||||
End point description |
HADS-A Anxiety level score
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group analysis | ||||||||||||
Statistical analysis description |
Between-group difference adjusted for baseline fatigue (FAS) scores.
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
16
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [20] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
3.4
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
1.6 | ||||||||||||
upper limit |
5.3 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [20] - Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
Anxiety (HADS-A) Week 30 | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 30 (6 weeks after completing medications)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Adjusted between-group difference | ||||||||||||
Statistical analysis description |
Adjusted between-group difference (adjusted for baseline fatigue (FAS) score)
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
20
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [21] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
3.4
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
1.6 | ||||||||||||
upper limit |
6.5 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [21] - Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
Depression (HADS-D) score week 12 | ||||||||||||
End point description |
HADS-D (depression symptoms) score
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12 - depression score
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Adjusted between-group mean difference | ||||||||||||
Statistical analysis description |
Between-group difference adjusted for baseline fatigue score
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
22
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [22] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-1.1
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-5.5 | ||||||||||||
upper limit |
3.3 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [22] - 1Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
Depression (HADS-D) Week 24 | ||||||||||||
End point description |
Depressive symptoms on HADS-D score
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 24 HADS-D score
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Adjusted between-group difference | ||||||||||||
Statistical analysis description |
Between-group difference adjusted for baseline fatigue score (by group)
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
16
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [23] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
2.7
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1.3 | ||||||||||||
upper limit |
6.7 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [23] - 1Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
Depression symptoms (HADS-D) week 30 | ||||||||||||
End point description |
Depressive symptoms (measured by HADS-D) at week 30, 6 weeks after completing trial medications
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 30
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Adjusted between-group difference | ||||||||||||
Statistical analysis description |
Mean between-group difference adjusted for baseline fatigue score
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
20
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [24] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
4.3
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
1.5 | ||||||||||||
upper limit |
7.1 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [24] - Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
KSQ-GHS Week 12 | ||||||||||||
End point description |
Kings Sarcoidosis Questionnaire - General Health Status
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Adjusted mean difference | ||||||||||||
Statistical analysis description |
Between-group adjusted mean difference (adjusted for baseline fatigue severity)
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
22
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [25] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-10.3
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-23.7 | ||||||||||||
upper limit |
-6.2 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [25] - Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
KSQ-GHS Week 24 | ||||||||||||
End point description |
Kings Sarcoidosis Questionnaire - General health status questionnaire
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group adjusted mean difference | ||||||||||||
Statistical analysis description |
Mean difference between groups adjusted for baseline fatigue severity
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
16
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [26] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-14.9
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-23.7 | ||||||||||||
upper limit |
-6.2 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [26] - Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
KSQ-GHS Week 30 | ||||||||||||
End point description |
Kings Sarcoidosis Questionnaire General Health Score
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 30
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group adjusted mean difference | ||||||||||||
Statistical analysis description |
Between-group mean difference adjusted for baseline fatigue score
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
20
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [27] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-8.8
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-20.6 | ||||||||||||
upper limit |
3.1 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [27] - Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
KSQ-Lung Week 12 | ||||||||||||
End point description |
Kings Sarcoidosis Questionnaire - Lung symptoms score
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Adjusted between-group difference | ||||||||||||
Statistical analysis description |
Between-group mean difference adjusted for baseline fatigue score
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
22
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [28] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-11.5
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-26.7 | ||||||||||||
upper limit |
3.7 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [28] - Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
KSQ-Lung Week 24 | ||||||||||||
End point description |
Kings sarcoidosis questionnaire - lung symptoms
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Adjusted between-group mean difference | ||||||||||||
Statistical analysis description |
Between-group mean difference
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
16
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [29] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-16.7
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-33.7 | ||||||||||||
upper limit |
0.2 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [29] - Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
KSQ-Lung Week 30 | ||||||||||||
End point description |
Kings sarcoidosis questionnaire - lung symptoms week 30
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 30
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group mean difference | ||||||||||||
Statistical analysis description |
Mean between-group difference adjusted for baseline fatigue score
|
||||||||||||
Comparison groups |
Placebo v Active treatment
|
||||||||||||
Number of subjects included in analysis |
20
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [30] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-11.9
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-31.6 | ||||||||||||
upper limit |
7.8 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [30] - Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
KSQ-Skin Week 12 | ||||||||||||
End point description |
Kings sarcoidosis questionnaire - skin symptoms
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group adjusted mean difference | ||||||||||||
Statistical analysis description |
Between-group mean difference adjusted for baseline fatigue score
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
22
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [31] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
0.5
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-15.9 | ||||||||||||
upper limit |
16.9 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [31] - Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
KSQ-Skin Week 24 | ||||||||||||
End point description |
Kings Sarcoidosis Questionnaire - skin symptoms
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group adjusted mean difference | ||||||||||||
Statistical analysis description |
Between-group adjusted mean difference (adjusted for baseline fatigue)
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
16
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [32] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-4.4
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-12.4 | ||||||||||||
upper limit |
3.7 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [32] - Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
KSQ-Skin Week 30 | ||||||||||||
End point description |
Kings sarcoidosis questionnaire - skin symptoms
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 30 (6 weeks after completing medications)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group adjusted mean difference | ||||||||||||
Statistical analysis description |
Between-group mean difference adjusted for baseline fatigue scores
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
20
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [33] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
7.8
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-9.2 | ||||||||||||
upper limit |
24.7 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [33] - Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
KSQ-Medications Week 12 | ||||||||||||
End point description |
Kings sarcoidosis questionnaire - medications symptoms
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Adjusted between-group mean difference | ||||||||||||
Statistical analysis description |
Between-group mean difference, adjusted for baseline fatigue severity
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
22
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [34] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
11.1
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-10.4 | ||||||||||||
upper limit |
32.7 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [34] - Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
KSQ-Medications Week 24 | ||||||||||||
End point description |
Kings sarcoidosis questionnaire - medication score
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group adjusted mean difference | ||||||||||||
Statistical analysis description |
Between-group difference adjusted for baseline fatigue score
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
16
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [35] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
4.4
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-6.3 | ||||||||||||
upper limit |
15.1 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [35] - Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
KSQ-Medications Week 30 | ||||||||||||
End point description |
Kings sarcoidosis questionnaire - medication symptoms
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 30
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group adjusted difference | ||||||||||||
Statistical analysis description |
Between-group mean difference adjusted for baseline fatigue severity
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
16
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [36] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-0.4
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-26.8 | ||||||||||||
upper limit |
26 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [36] - Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
KSQ-Eye Week 12 | ||||||||||||
End point description |
Kings sarcoidosis questionnaire - eye symptoms
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group adjusted mean difference | ||||||||||||
Statistical analysis description |
Between-group mean difference adjusted for baseline fatigue severity
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
22
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [37] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
3
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-16.4 | ||||||||||||
upper limit |
22.4 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [37] - Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
KSQ-Eye Week 24 | ||||||||||||
End point description |
Kings sarcoidosis questionnaire - eye symptoms
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group adjusted mean difference | ||||||||||||
Statistical analysis description |
Between-group mean difference adjusted for baseline fatigue severity
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
16
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [38] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-6.3
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-29.3 | ||||||||||||
upper limit |
16.7 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [38] - Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
KSQ-Eye Week 30 | ||||||||||||
End point description |
Kings sarcoidosis questionnaire eye symptoms
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 30
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group adjusted mean difference | ||||||||||||
Statistical analysis description |
Between group mean difference adjusted for baseline fatigue severity
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
20
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [39] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-6.9
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-19.4 | ||||||||||||
upper limit |
5.6 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [39] - Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
KSQ-Composite score Week 12 | ||||||||||||
End point description |
Kings sarcoidosis questionnaire - Composite score
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group adjusted mean difference | ||||||||||||
Statistical analysis description |
Between-group mean difference adjusted for baseline fatigue severity
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
22
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [40] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-11.1
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-20 | ||||||||||||
upper limit |
-2.2 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [40] - Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
KSQ-Composite score Week 24 | ||||||||||||
End point description |
Kings sarcoidosis questionnaire composite output
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group adjusted mean difference | ||||||||||||
Statistical analysis description |
Between group mean difference adjusted for baseline fatigue severity
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
16
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [41] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-12.4
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-20.6 | ||||||||||||
upper limit |
-4.2 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [41] - Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
KSQ-Composite score Week 30 | ||||||||||||
End point description |
Kings sarcoidosis questionnaire composite outcome
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 30
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group adjusted mean difference | ||||||||||||
Statistical analysis description |
Between-group mean difference adjusted by baseline fatigue severity
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
20
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [42] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-9.6
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-18 | ||||||||||||
upper limit |
-1.2 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [42] - Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
EQ5D Utility Week 12 | ||||||||||||
End point description |
EQ5D health utility score
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group adjusted mean difference | ||||||||||||
Statistical analysis description |
Between group mean difference adjusted for baseline fatigue severity
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
22
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [43] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-0.005
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.121 | ||||||||||||
upper limit |
0.111 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [43] - 1Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
EQ5D Utility Week 24 | ||||||||||||
End point description |
EQ5D-derived health utility value
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group mean adjusted difference | ||||||||||||
Statistical analysis description |
Between group mean difference adjusted for baseline fatigue severity
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
16
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [44] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-0.139
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.214 | ||||||||||||
upper limit |
-0.065 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [44] - 1Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
EQ5D Utility Week 30 | ||||||||||||
End point description |
EQ5D-derived health utility value
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 30 (6 weeks after completing medications)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group mean adjusted difference | ||||||||||||
Statistical analysis description |
Between-group mean difference adjusted for baseline fatigue severity
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
16
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [45] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-0.052
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.209 | ||||||||||||
upper limit |
0.104 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [45] - 1Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
SF6D Health Utility Week 12 | ||||||||||||
End point description |
SF6D-derived health utility score
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group adjusted mean difference | ||||||||||||
Statistical analysis description |
Between-group mean difference adjusted for baseline fatigue severity
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
22
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [46] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-0.097
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.173 | ||||||||||||
upper limit |
-0.021 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [46] - 1Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
SF6D Health Utility Week 24 | ||||||||||||
End point description |
SF6D-derived health utility score
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group adjusted mean difference | ||||||||||||
Statistical analysis description |
Between-group mean difference adjusted for baseline fatigue severity
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
16
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [47] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-0.161
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.266 | ||||||||||||
upper limit |
-0.056 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [47] - 1Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
SF6D Health Utility Week 30 | ||||||||||||
End point description |
SF6D-derived health utility value
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 30 (6 weeks after medication completion)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group adjusted mean difference | ||||||||||||
Statistical analysis description |
Between-group mean difference adjusted for baseline fatigue severity
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
20
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [48] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-0.13
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.217 | ||||||||||||
upper limit |
-0.043 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [48] - 1Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
EQ-VAS Health Utility Week 12 | ||||||||||||
End point description |
EQ-VAS derived health utility
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group adjusted mean difference | ||||||||||||
Statistical analysis description |
Between-group mean difference adjusted for baseline fatigue severity
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
22
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [49] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-3.6
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-20.9 | ||||||||||||
upper limit |
13.6 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [49] - 1Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
EQ-VAS Health Utility Week 24 | ||||||||||||
End point description |
EQ-VAS derived health utility score
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group adjusted mean difference | ||||||||||||
Statistical analysis description |
Between-group mean difference adjusted for baseline fatigue severity
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
16
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [50] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-7.6
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-32.4 | ||||||||||||
upper limit |
17.2 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [50] - 1Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
EQ-VAS Health Utility Week 30 | ||||||||||||
End point description |
Health utility score derived from EQ-VAS questionnaire
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 30 (6 weeks after completing medications)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group adjusted mean difference | ||||||||||||
Statistical analysis description |
Between-group mean difference adjusted for baseline fatigue severity
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
20
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [51] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
4.5
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-10.7 | ||||||||||||
upper limit |
19.6 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [51] - 1Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
Sleep Quality - PSQI score | ||||||||||||
End point description |
Pittsburgh Sleep Quality Index Questionnaire sleep quality
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group mean adjusted difference | ||||||||||||
Statistical analysis description |
Between group mean difference adjusted for baseline fatigue severity
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
14
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [52] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
4.4
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-3.2 | ||||||||||||
upper limit |
11.9 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [52] - 1Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
Sleep Quality - PSQI score (Week 24) | ||||||||||||
End point description |
Pittsburgh Sleep Quality Index questionnaire score
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group mean adjusted difference | ||||||||||||
Statistical analysis description |
Between-group mean difference adjusted for baseline fatigue severity
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
14
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [53] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
0.9
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-23.3 | ||||||||||||
upper limit |
25.1 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [53] - 1Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
Sleep efficiency | ||||||||||||
End point description |
Sleep efficiency, Higher values indicate better sleep efficiency (higher percentage of the time in bed spent asleep)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group mean adjusted difference | ||||||||||||
Statistical analysis description |
Between group mean difference adjusted for baseline fatigue severity
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
14
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [54] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-12.4
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-40.3 | ||||||||||||
upper limit |
68 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [54] - 1Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
Sleep efficiency - week 24 | ||||||||||||
End point description |
Sleep efficiency (time asleep as a percentage of time in bed)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between group adjusted mean difference | ||||||||||||
Statistical analysis description |
Between group mean difference adjusted for baseline fatigue severity
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
14
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [55] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
1.6
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-64.7 | ||||||||||||
upper limit |
68 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [55] - 1Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
FEV1 percentage predicted - week 12 | ||||||||||||
End point description |
Forced expiratory volume in 1 second percentage predicted value
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Adjusted mean difference | ||||||||||||
Statistical analysis description |
Between group adjusted mean difference
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
16
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [56] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
8.2
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-2.2 | ||||||||||||
upper limit |
18.6 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [56] - 1Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
FEV1 percentage predicted - week 24 | ||||||||||||
End point description |
Forced expiratory volume in 1 second percentage predicted value
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group adjusted mean difference | ||||||||||||
Statistical analysis description |
Between-group mean difference adjusted for baseline fatigue severity
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
16
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [57] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
6.4
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-6.6 | ||||||||||||
upper limit |
19.3 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [57] - 1Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
Forced vital capacity percentage predicted - week 12 | ||||||||||||
End point description |
Forced vital capacity percentage predicted value
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group adjusted mean difference | ||||||||||||
Statistical analysis description |
Between group adjusted mean difference
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
16
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [58] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
8.2
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1.4 | ||||||||||||
upper limit |
23.3 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [58] - 1Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
MSWT Week 12 | ||||||||||||
End point description |
Modified shuttle walk test distance (metres)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between group adjusted mean difference | ||||||||||||
Statistical analysis description |
Between group mean difference adjusted for baseline fatigue severity
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
16
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [59] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
56.4
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-73.9 | ||||||||||||
upper limit |
186.6 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [59] - 1Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
MSWT Week 24 | ||||||||||||
End point description |
Modified shuttle walk test distance (metres)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between group adjusted mean difference | ||||||||||||
Statistical analysis description |
Between-group difference adjusted for baseline fatigue severity
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
11
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [60] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
43.9
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-216.3 | ||||||||||||
upper limit |
304.1 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [60] - 1Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
MVPA minutes per day | ||||||||||||
End point description |
Time in moderate or vigorous physical activity per day
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group adjusted mean difference | ||||||||||||
Statistical analysis description |
Between group mean difference adjusted for baseline fatigue severity
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
19
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [61] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
14.7
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-29.1 | ||||||||||||
upper limit |
58.6 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [61] - 1Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
MVPA minutes per day (week 24) | ||||||||||||
End point description |
Time in moderate or vigorous activity per day (minutes)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between group adjusted mean difference | ||||||||||||
Statistical analysis description |
Between group mean difference adjusted for baseline fatigue severity
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
15
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [62] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
24.6
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-16.8 | ||||||||||||
upper limit |
65.9 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [62] - 1Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
MVPA10 Week 12 | ||||||||||||
End point description |
Time in moderate or vigorous physical activity (10 minute bout criteria)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between group adjusted mean difference | ||||||||||||
Statistical analysis description |
Between group mean difference adjusted for baseline fatigue severity
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
19
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [63] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-6.7
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-27.2 | ||||||||||||
upper limit |
13.8 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [63] - 1Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
|||||||||||||
End point title |
MVPA10 - Week 24 | ||||||||||||
End point description |
Time in moderate or vigorous physical activity (ten minute bout criteria) in minutes per day.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between group adjusted mean difference | ||||||||||||
Statistical analysis description |
Between group mean difference adjusted for baseline fatigue severity
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
15
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [64] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-6.7
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-27.2 | ||||||||||||
upper limit |
13.8 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [64] - 1Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
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|
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End point title |
Sedentary time per day - week 12 | ||||||||||||
End point description |
Time in sedentary behaviours per day
|
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End point type |
Secondary
|
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End point timeframe |
Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between group adjusted mean difference | ||||||||||||
Statistical analysis description |
Between group mean difference adjusted for baseline fatigue severity
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
19
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [65] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-167.3
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-320.9 | ||||||||||||
upper limit |
-13.8 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [65] - 1Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
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End point title |
sedentary time per day - week 24 | ||||||||||||
End point description |
Time spent in sedentary behaviours per day
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between group adjusted mean difference | ||||||||||||
Statistical analysis description |
Between group mean difference adjusted for baseline fatigue severity
|
||||||||||||
Comparison groups |
Active treatment v Placebo
|
||||||||||||
Number of subjects included in analysis |
15
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [66] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-139.2
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-341.4 | ||||||||||||
upper limit |
63 | ||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||
| Notes [66] - 1Mean difference is equivalent to the methylphenidate group value minus the placebo group value. Positive values indicate the methylphenidate group value was higher than the placebo group, negative values indicate the methylphenidate group value was lower than the placebo group. |
|||||||||||||
|
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Adverse events information
|
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Timeframe for reporting adverse events |
AEs assessed at week 1,2,3,4,5,6,8,10,12,14,16,18,20,22,24
|
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Adverse event reporting additional description |
Weeks 2,4,6,12,18 and 24 were face-to-face visits with assessment of patients in person. This included blood tests, ECGs, physical observations.
Weeks 1,3,5,8,10,14,16,20 and 22 were telephone calls to record any AEs.
Participants could also contact the trial team if any problems occurred between visits.
|
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
|
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Dictionary name |
CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
4.0
|
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|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Methylphenidate
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Fifteen participants receiving methylphenidate | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Seven participants receiving placebo | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0.1% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
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|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
17 Apr 2017 |
After four months of recruitment it became apparent that the recruitment rate was
below that expected. In order to increase the recruitment period, two amendments
were made. Firstly, the ability to recruit participants from PIC sites in the eastern
region was added, with Royal Papworth Hospital and Addenbrooke’s hospital
operating in this capacity. Secondly, in order to increase the recruitment phase (and
maximise the time participants could enter the study without reducing the overall
study duration), follow-up for participants recruited between December 2017 and
March 2018 was truncated. Participants randomised between 01/12/2017 and
01/02/2018 received study medication for 18 weeks, plus an additional two weeks
if a down-titration period at the end of the study was required; participants
randomised between 02/02/2018 and 02/03/2018 received study medication for 12
weeks, plus an additional two weeks if down-titration was required. The last date of
follow-up was fixed at 06/07/2018.
As part of this substantial amendment, two additional outcome measures were
added. The PSQI and Exit questionnaires were administered to patients entering the
study after 23/05/2017 according to the questionnaire schedule in table 1;
participants who had already commenced the study were administered the
additional questionnaires if they consented to completing these additional
measurements. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| The individual AEs are archived and not immediately available, the overall data results are presented and entered here. | |||
Online references |
|||
| http://www.ncbi.nlm.nih.gov/pubmed/29208618 http://www.ncbi.nlm.nih.gov/pubmed/34020962 |
|||
