Clinical Trial Results:
A pilot study on the effects of an alternate-day corticosteroid regimen in children with active crohn’s disease
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Summary
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EudraCT number |
2010-022017-26 |
Trial protocol |
GB |
Global end of trial date |
11 Mar 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
29 Mar 2020
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First version publication date |
29 Mar 2020
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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 |
R01116
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
REC reference: 10/H1010/53 | ||
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Sponsors
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Sponsor organisation name |
Manchester University NHS Foundation Trust
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Sponsor organisation address |
Oxford Road, Manchester, United Kingdom, M13 9WL
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Public contact |
Dr Lynne Webster, Manchester University NHS Foundation Trust, research.sponsor@mft.nhs.uk
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Scientific contact |
Dr Lynne Webster, Manchester University NHS Foundation Trust, research.sponsor@mft.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 |
11 Mar 2014
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
11 Mar 2014
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To investigate the feasibility of a RCT to compare an alternate-day prednisolone regimen with a daily-dose regimen:
a. to assess whether the research protocol is realistic and workable
b. to identify logistical problems which might occur using the proposed protocol
c. to assess the likely success of recruitment and determine period of recruitment
d. to determine if there is likely to be significant attrition
e. to determine what resources (finance, staff) will be needed for the main study
f. to test the outcome measures and their suitability, practicality, statistical properties and utility.
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Protection of trial subjects |
The potential risks of this study include adverse reactions to prednisolone and the small risk of venepuncture. However, the potential benefits of this study far outweigh the potential risks. We do not expect the occurrence of prednisolone adverse effects to be any worse than what is seen in routine clinical practice. Patients who are randomised to alternateday therapy may however experience fewer side effects although it is likely that alternateday therapy may be less effective. We will closely monitor all participants for any evidence of adverse effects and also of disease activity over the study period. Venepuncture will be undertaken by experienced nurses or doctors and where appropriate, a local analgesia will be applied in order to minimise the pain and discomfort associated with bloodtaking.
Participants and/or their parents/carers will have to spend some time to complete the quality of life questionnaire but this questionnaire is quite simple and each should not take more than 10 minutes to complete.
Apart from being assigned to either alternateday therapy or dailydose therapy, patients in both groups will be treated in exactly the same way.
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Background therapy |
Routine care in both groups will remain as it is in normal practice. | ||
Evidence for comparator |
N/A - no comparator used. | ||
Actual start date of recruitment |
31 Aug 2011
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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: 7
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Worldwide total number of subjects |
7
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EEA total number of subjects |
7
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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) |
1
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Adolescents (12-17 years) |
6
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients who satisfied entry criteria were approached by an investigator who provided full information about the study and obtain written informed consent. By means of computer-generated random number, participants were randomly allocated to one of two groups: Group 1 (alternateday corticosteroid regimen) or Group 2 (dailydose corticosteroid regim | ||||||||||||||||||
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Pre-assignment
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Screening details |
Inclusion: 1) patients aged 8 to 17 years 2) diagnosis of Crohn’s disease by established clinical, endoscopic, histological and radiological criteria 3) clinically active disease defined as a paediatric Crohn’s disease activity index (PCDAI) score of >15 4) clinical decision made to commence oral prednisolone 5) parental and child consent | ||||||||||||||||||
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Pre-assignment period milestones
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Number of subjects started |
7 | ||||||||||||||||||
Number of subjects completed |
7 | ||||||||||||||||||
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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 |
Not blinded | ||||||||||||||||||
Blinding implementation details |
N/A - this was an open label trial.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Group 1 (alternate-day corticosteroid regimen) | ||||||||||||||||||
Arm description |
Group 1 (alternate-day corticosteroid regimen): oral prednisolone 2 mg/kg/day (max 40 mg) for 3 weeks, then switch to alternate-day dosing and reduce dose by 5mg after every week. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Prednisolone
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Investigational medicinal product code |
A07EA01
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Other name |
PL 06464/0914
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Pharmaceutical forms |
Soluble tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Oral prednisolone 2 mg/kg/day (max 40 mg) for 3 weeks
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Arm title
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Group 2 (daily-dose corticosteroid regimen) | ||||||||||||||||||
Arm description |
Group 2 (daily-dose corticosteroid regimen): oral Prednisolone 2 mg/kg/day (max 40 mg) for 3 weeks, then reduce dose by 5 mg every week as daily dose. Participants will take each daily dose in the morning. | ||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||
Investigational medicinal product name |
Prednisolone
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Investigational medicinal product code |
A07EA01
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Other name |
PL 06464/0914
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Pharmaceutical forms |
Soluble tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Oral Prednisolone 2 mg/kg/day (max 40 mg) for 3 weeks, then reduce dose by 5 mg every week as daily dose.
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End points reporting groups
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Reporting group title |
Group 1 (alternate-day corticosteroid regimen)
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Reporting group description |
Group 1 (alternate-day corticosteroid regimen): oral prednisolone 2 mg/kg/day (max 40 mg) for 3 weeks, then switch to alternate-day dosing and reduce dose by 5mg after every week. | ||
Reporting group title |
Group 2 (daily-dose corticosteroid regimen)
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Reporting group description |
Group 2 (daily-dose corticosteroid regimen): oral Prednisolone 2 mg/kg/day (max 40 mg) for 3 weeks, then reduce dose by 5 mg every week as daily dose. Participants will take each daily dose in the morning. | ||
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End point title |
Clinical remission defined as a Paediatric Crohn’s Disease Activity Index (PCDAI) score of < 10 [1] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
The PCDAI will be assessed at baseline or screening, 3, 6, and 11 weeks.
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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: Data analysis was not conducted as the trial was terminated early. |
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| Notes [2] - The trial was terminated early so no results were analysed. [3] - The trial was terminated early so no results were analysed. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Health related quality of life | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
QOL scores will be assessed at baseline, six and 11 weeks.
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| Notes [4] - The trial was terminated early so no results were analysed. [5] - The trial was terminated early so no results were analysed. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Clinical response – defined as a 15 point drop of PCDAI from baseline | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Clinical response will be defined as a 15 point drop of PCDAI from baseline values.
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| Notes [6] - The trial was terminated early so no results were analysed. [7] - The trial was terminated early so no results were analysed. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Effect of prednisolone therapy on bone formation and bone resorpton | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Samples will be analysed at baseline, 6 weeks, and 11 weeks for biochemical markers of bone formation.
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| Notes [8] - The trial was terminated early so no results were analysed. [9] - The trial was terminated early so no results were analysed. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Effect of Prednisolone therapy on Insulin-like Growth Factor 1 | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Serum IGF-1 will be assessed at baseline and at 11 weeks.
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| Notes [10] - The trial was terminated early so no results were analysed. [11] - The trial was terminated early so no results were analysed. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Adrenal responsiveness to ACH measured using a standard synacthen test protocol | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Adrenal responsiveness to Adrenocorticotrophic Hormone (ACTH) will be measured using a standard synacthen test protocol
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| Notes [12] - The trial was terminated early so no results were analysed. [13] - The trial was terminated early so no results were analysed. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Adverse effects | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At each scheduled visit (3, 6, and 11 weeks), the investigator will ask each participant to report any event(s) that the participant, or the parents, believe might reasonably be related to participation in this study.
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| Notes [14] - The trial was terminated early so no results were analysed. [15] - The trial was terminated early so no results were analysed. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Adherence to Prednisolone Therapy | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Using pill counts conducted at 3, 6, and 11 weeks.
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| Notes [16] - The trial was terminated early so no results were analysed. [17] - The trial was terminated early so no results were analysed. |
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| No statistical analyses for this end point | ||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
An adverse event is the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after the study has commenced, even if not considered to be related to the investigational medicinal product.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
1
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Reporting groups
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Reporting group title |
Group 1 (alternate-day corticosteroid regimen)
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Reporting group description |
Group 1 (alternate-day corticosteroid regimen): oral prednisolone 2 mg/kg/day (max 40 mg) for 3 weeks, then switch to alternate-day dosing and reduce dose by 5mg after every week. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Group 2 (daily-dose corticosteroid regimen)
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Reporting group description |
Group 2 (daily-dose corticosteroid regimen): oral Prednisolone 2 mg/kg/day (max 40 mg) for 3 weeks, then reduce dose by 5 mg every week as daily dose. Participants will take each daily dose in the morning. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Notes [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: Three participants withdrew before treatment was administered. |
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Notes [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: Three participants withdrew before treatment was administered. [3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: Three participants withdrew before treatment was administered. [4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: Three participants withdrew before treatment was administered. [5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: Three participants withdrew before treatment was administered. [6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: Three participants withdrew before treatment was administered. [7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: Three participants withdrew before treatment was administered. [8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: Three participants withdrew before treatment was administered. [9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: Three participants withdrew before treatment was administered. [10] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: Three participants withdrew before treatment was administered. [11] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: Three participants withdrew before treatment was administered. [12] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: Three participants withdrew before treatment was administered. [13] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: Three participants withdrew before treatment was administered. [14] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: Three participants withdrew before treatment was administered. [15] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: Three participants withdrew before treatment was administered. [16] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: Three participants withdrew before treatment was administered. |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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02 May 2012 |
Due to local changes regarding blood sample collection and analysis it has become necessary to amend the protocol. In order to avoid amendments to the protocol every time the method of sample collection or analysis is amended, it has been decided to remove the laboratory section (sample collection, storage and analysis) to a separate laboratory manual. This will be version controlled by the research team and amended as required. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Only 4 of a planned 27 patients completed treatment which is insufficient to allow a complete evaluation of the results and complete the overall risk benefit assessment of the IMP. | |||
