Clinical Trial Results:
BREATHER (PENTA 16): Short-cycle therapy (SCT) (5 days on/ 2 days off) in young people with chronic HIV-infection
Summary
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EudraCT number |
2009-012947-40 |
Trial protocol |
IE GB ES DK BE DE |
Global end of trial date |
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Results information
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Results version number |
v1 |
This version publication date |
04 Feb 2017
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First version publication date |
04 Feb 2017
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Other versions |
v2 |
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 |
PENTA16
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Additional study identifiers
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ISRCTN number |
ISRCTN97755073 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
The PENTA foundation
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Sponsor organisation address |
Torre della Ricerca Pediatrica Corso Stati Uniti 4, Padova, Italy, 35127
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Public contact |
University College London, University College London, penta.mrcctu@ucl.ac.uk
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Scientific contact |
University College London, University College London, penta.mrcctu@ucl.ac.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 |
Interim
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Date of interim/final analysis |
31 Jul 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Jul 2014
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Global end of trial reached? |
No
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General information about the trial
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Main objective of the trial |
The overall aim of the BREATHER trial is to evaluate the role of Short-Cycle Therapy (SCT) in the management of HIV-infected young people who have responded well to antiretroviral therapy (ART) and to determine whether young people with chronic HIV infection undergoing Short-Cycle Therapy of five days on ART and two days off maintain the same level of viral load suppression as those on continuous therapy, over 48 weeks.
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Protection of trial subjects |
In order to assess the safety of the SCT strategy, a pilot study was carried out in 32 young people, who were seen on the Monday morning following having Saturday and Sunday off treatment. Their viral loads were assessed on this visit and the main trial did not commense until the IDMC had confirmed they had no saftey concerns as a result of the pilot phase.
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Background therapy |
Every young person were on a first-line HAART regimen containing at least 2 NRTI/NtRTIs and EFV. | ||
Evidence for comparator |
Current WHO guidelines recommend a first-line ART regimen containing 2 NRTI/NtRTIs and EFV for treatment of HIV in children. | ||
Actual start date of recruitment |
01 Apr 2011
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety, Efficacy, Scientific research | ||
Long term follow-up duration |
2 Years | ||
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 |
Spain: 11
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Country: Number of subjects enrolled |
United Kingdom: 26
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Country: Number of subjects enrolled |
Belgium: 2
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Country: Number of subjects enrolled |
Denmark: 3
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Country: Number of subjects enrolled |
Germany: 3
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Country: Number of subjects enrolled |
Ireland: 3
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Country: Number of subjects enrolled |
Thailand: 36
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Country: Number of subjects enrolled |
Argentina: 11
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Country: Number of subjects enrolled |
United States: 14
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Country: Number of subjects enrolled |
Uganda: 70
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Country: Number of subjects enrolled |
Ukraine: 20
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Worldwide total number of subjects |
199
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EEA total number of subjects |
48
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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) |
53
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Adolescents (12-17 years) |
104
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Adults (18-64 years) |
42
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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 |
- | |||||||||||||||
Pre-assignment
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Screening details |
- | |||||||||||||||
Pre-assignment period milestones
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Number of subjects started |
225 [1] | |||||||||||||||
Number of subjects completed |
199 | |||||||||||||||
Pre-assignment subject non-completion reasons
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Reason: Number of subjects |
Consent withdrawn by subject: 3 | |||||||||||||||
Reason: Number of subjects |
Protocol deviation: 21 | |||||||||||||||
Reason: Number of subjects |
Car crash prevented them making randomsation visit: 1 | |||||||||||||||
Reason: Number of subjects |
Unreliable attendance: 1 | |||||||||||||||
Notes [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: 225 young people were screened, but 199 randomised. Reasons for not randomising are documented here. |
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Period 1
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Period 1 title |
Main 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 | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Continuous therapy | |||||||||||||||
Arm description |
Patients randomised to continuing their ART strategy, taking ART every day. | |||||||||||||||
Arm type |
No intervention | |||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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Short Cycle Therapy | |||||||||||||||
Arm description |
Patients take their ART as normal for 5 days a week, with a break at the weekends, taking no ART for 2 days every week. The only product enterred here is Efavirenz, as all young people in the trial were on Efavirenz. However, it is not the drug that is being investigated in this trial, it is the strategy in which the ART regimen is taken. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Efavirenz
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Dosed as perscribed by the clinician.
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Baseline characteristics reporting groups
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Reporting group title |
Continuous therapy
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Reporting group description |
Patients randomised to continuing their ART strategy, taking ART every day. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Short Cycle Therapy
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Reporting group description |
Patients take their ART as normal for 5 days a week, with a break at the weekends, taking no ART for 2 days every week. The only product enterred here is Efavirenz, as all young people in the trial were on Efavirenz. However, it is not the drug that is being investigated in this trial, it is the strategy in which the ART regimen is taken. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Continuous therapy
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Reporting group description |
Patients randomised to continuing their ART strategy, taking ART every day. | ||
Reporting group title |
Short Cycle Therapy
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Reporting group description |
Patients take their ART as normal for 5 days a week, with a break at the weekends, taking no ART for 2 days every week. The only product enterred here is Efavirenz, as all young people in the trial were on Efavirenz. However, it is not the drug that is being investigated in this trial, it is the strategy in which the ART regimen is taken. |
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End point title |
Virological failure (>=50c/ml confirmed). | |||||||||||||||
End point description |
The primary endpoint was a confirmed viral load >=50c/ml within 54 weeks of randomisation.
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End point type |
Primary
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End point timeframe |
Any time from randomisation to 48(+6) weeks after randomisation.
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Statistical analysis title |
Primary analysis - diff in adj. KM estimates | |||||||||||||||
Statistical analysis description |
Difference in adjusted (for stratification factors) Kaplan-Meier survival function estimates at 54 weeks after randomisation.
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Comparison groups |
Continuous therapy v Short Cycle Therapy
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Number of subjects included in analysis |
199
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [1] | |||||||||||||||
Method |
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Parameter type |
Mean difference (final values) | |||||||||||||||
Point estimate |
-0.012
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Confidence interval |
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level |
90% | |||||||||||||||
sides |
2-sided
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lower limit |
-0.073 | |||||||||||||||
upper limit |
0.049 | |||||||||||||||
Notes [1] - Non-inferiority margin = 12%. Calculated SCT arm survival function - CT arm survival function, so if the upper bound of the 90% confidence interval was <0.12, the results were consistent with non-inferiority of SCT compared with CT. |
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Statistical analysis title |
Secondary analysis - unadjusted diff | |||||||||||||||
Statistical analysis description |
Difference in Kaplan-Meier survival function estimates at 54 weeks after randomisation.
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Comparison groups |
Short Cycle Therapy v Continuous therapy
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Number of subjects included in analysis |
199
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [2] | |||||||||||||||
Method |
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Parameter type |
Mean difference (final values) | |||||||||||||||
Point estimate |
-0.011
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Confidence interval |
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level |
90% | |||||||||||||||
sides |
2-sided
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lower limit |
-0.068 | |||||||||||||||
upper limit |
0.046 | |||||||||||||||
Notes [2] - Non-inferiority margin = 12%. Calculated SCT arm survival function - CT arm survival function, so if the upper bound of the 90% confidence interval was <0.12, the results were consistent with non-inferiority of SCT compared with CT. |
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Statistical analysis title |
Secondary analysis - crude diff | |||||||||||||||
Statistical analysis description |
Difference in proportion of YP with confirmed VL>=50c/ml.
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Comparison groups |
Short Cycle Therapy v Continuous therapy
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Number of subjects included in analysis |
199
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [3] | |||||||||||||||
Method |
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Parameter type |
Mean difference (final values) | |||||||||||||||
Point estimate |
-0.009
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Confidence interval |
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level |
90% | |||||||||||||||
sides |
2-sided
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lower limit |
-0.067 | |||||||||||||||
upper limit |
0.048 | |||||||||||||||
Notes [3] - Non-inferiority margin = 12%. Calculated proportion of YP with virological failure in the SCT arm - proportion of YP with virological failure in the CT arm, so if the upper bound of the 90% confidence interval was <0.12, the results were consistent with non-inferiority of SCT compared with CT. |
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Statistical analysis title |
Secondary analysis - unadj. Cox model | |||||||||||||||
Statistical analysis description |
Cox model examining time to confirmed viral load >=50c/ml
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Comparison groups |
Continuous therapy v Short Cycle Therapy
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Number of subjects included in analysis |
199
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||||||||
P-value |
= 0.755 [4] | |||||||||||||||
Method |
Regression, Cox | |||||||||||||||
Parameter type |
Hazard ratio (HR) | |||||||||||||||
Point estimate |
0.84
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Confidence interval |
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level |
90% | |||||||||||||||
sides |
2-sided
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lower limit |
0.34 | |||||||||||||||
upper limit |
2.1 | |||||||||||||||
Notes [4] - Non-significant difference between arms. |
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Statistical analysis title |
Secondary analysis - adj. Cox model | |||||||||||||||
Statistical analysis description |
Cox model examining time to confirmed viral load >=50c/ml, adjusting for stratification factors.
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Comparison groups |
Short Cycle Therapy v Continuous therapy
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Number of subjects included in analysis |
199
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||||||||
P-value |
= 0.743 [5] | |||||||||||||||
Method |
Regression, Cox | |||||||||||||||
Parameter type |
Hazard ratio (HR) | |||||||||||||||
Point estimate |
0.83
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Confidence interval |
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level |
90% | |||||||||||||||
sides |
2-sided
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lower limit |
0.33 | |||||||||||||||
upper limit |
2.08 | |||||||||||||||
Notes [5] - Non-significant difference between arms. |
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End point title |
Virological failure (>=400c/ml confirmed). | |||||||||||||||
End point description |
Confirmed viral load >=400c/ml within 54 weeks of randomisation.
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End point type |
Secondary
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End point timeframe |
Any time from randomisation to 48(+6) weeks after randomisation.
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Statistical analysis title |
Diff. in adj. KM estimates | |||||||||||||||
Statistical analysis description |
Difference in adjusted (for stratification factors) Kaplan-Meier survival function estimates at 54 weeks after randomisation.
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Comparison groups |
Continuous therapy v Short Cycle Therapy
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Number of subjects included in analysis |
199
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [6] | |||||||||||||||
Method |
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Parameter type |
Mean difference (final values) | |||||||||||||||
Point estimate |
-0.021
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Confidence interval |
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level |
90% | |||||||||||||||
sides |
2-sided
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lower limit |
-0.062 | |||||||||||||||
upper limit |
0.019 | |||||||||||||||
Notes [6] - Calculated SCT arm survival function - CT arm survival function, so if the upper bound of the 90% confidence interval was <0.12, the results were consistent with non-inferiority of SCT compared with CT. |
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Statistical analysis title |
Unadj. diff. in KM estimates | |||||||||||||||
Statistical analysis description |
Difference in Kaplan-Meier survival function estimates at 54 weeks after randomisation.
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Comparison groups |
Continuous therapy v Short Cycle Therapy
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Number of subjects included in analysis |
199
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [7] | |||||||||||||||
Method |
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Parameter type |
Mean difference (final values) | |||||||||||||||
Point estimate |
-0.02
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Confidence interval |
||||||||||||||||
level |
90% | |||||||||||||||
sides |
2-sided
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lower limit |
-0.061 | |||||||||||||||
upper limit |
0.02 | |||||||||||||||
Notes [7] - Calculated SCT arm survival function - CT arm survival function, so if the upper bound of the 90% confidence interval was <0.12, the results were consistent with non-inferiority of SCT compared with CT. |
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Statistical analysis title |
Crude diff. in proportion | |||||||||||||||
Statistical analysis description |
Difference in proportion of YP with confirmed VL>=400c/ml.
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Comparison groups |
Continuous therapy v Short Cycle Therapy
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Number of subjects included in analysis |
199
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [8] | |||||||||||||||
Method |
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Parameter type |
Mean difference (final values) | |||||||||||||||
Point estimate |
-0.02
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Confidence interval |
||||||||||||||||
level |
90% | |||||||||||||||
sides |
2-sided
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|||||||||||||||
lower limit |
-0.06 | |||||||||||||||
upper limit |
0.02 | |||||||||||||||
Notes [8] - Calculated proportion of YP with virological failure in the SCT arm - proportion of YP with virological failure in the CT arm, so if the upper bound of the 90% confidence interval was <0.12, the results were consistent with non-inferiority of SCT compared with CT. |
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Statistical analysis title |
Unadj. Cox model | |||||||||||||||
Statistical analysis description |
Cox model examining time to confirmed viral load >=400c/ml
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Comparison groups |
Continuous therapy v Short Cycle Therapy
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Number of subjects included in analysis |
199
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||||||||
P-value |
= 0.4 | |||||||||||||||
Method |
Regression, Cox | |||||||||||||||
Parameter type |
Hazard ratio (HR) | |||||||||||||||
Point estimate |
0.48
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Confidence interval |
||||||||||||||||
level |
90% | |||||||||||||||
sides |
2-sided
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lower limit |
0.12 | |||||||||||||||
upper limit |
2.01 | |||||||||||||||
Statistical analysis title |
Adj. Cox model | |||||||||||||||
Statistical analysis description |
Cox model examining time to confirmed viral load >=400c/ml, adjusting for stratification factors.
|
|||||||||||||||
Comparison groups |
Continuous therapy v Short Cycle Therapy
|
|||||||||||||||
Number of subjects included in analysis |
199
|
|||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||
Analysis type |
other | |||||||||||||||
P-value |
= 0.399 | |||||||||||||||
Method |
Regression, Cox | |||||||||||||||
Parameter type |
Hazard ratio (HR) | |||||||||||||||
Point estimate |
0.48
|
|||||||||||||||
Confidence interval |
||||||||||||||||
level |
90% | |||||||||||||||
sides |
2-sided
|
|||||||||||||||
lower limit |
0.12 | |||||||||||||||
upper limit |
2 |
|
|||||||||||||
End point title |
SCT change strategy to continuous therapy [9] | ||||||||||||
End point description |
Any young person that changed strategy from SCT to return to taking daily ART, and reasons for changing.
The protocol states that young people should return to continuous therapy if they experience the primary endpoint, or have 3 viral load "blips" >=50c/ml, which have a subsequent VL reading that is <50c/ml.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Any time from randomisation to week 48(+6).
|
||||||||||||
Notes [9] - 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: This is only applicable to those randomised to SCT and therefore cannot be reported for those on CT, as they are all already taking their ART every day. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Changes in ART regimen | |||||||||||||||
End point description |
Number of individuals on a different ART regimen at week 48 to at week 0.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Randomisation to week 48(+6).
|
|||||||||||||||
|
||||||||||||||||
Notes [10] - 1 young person lost to follow up before week 48 visit |
||||||||||||||||
Statistical analysis title |
Snapshot comparison at week 48 visit | |||||||||||||||
Statistical analysis description |
Fisher's exact test comparing number of young people still on their randomised regimen at week 48 from each arm.
|
|||||||||||||||
Comparison groups |
Continuous therapy v Short Cycle Therapy
|
|||||||||||||||
Number of subjects included in analysis |
198
|
|||||||||||||||
Analysis specification |
Post-hoc
|
|||||||||||||||
Analysis type |
equivalence | |||||||||||||||
P-value |
= 0.104 | |||||||||||||||
Method |
Fisher exact | |||||||||||||||
Confidence interval |
|
|||||||||||||||||||
End point title |
Young people with major resistance mutations - any class | ||||||||||||||||||
End point description |
Resistance tests were performed on everyone that reached the primary endpoint. "Major mutation" defined as in Johnson et. al., 2013, Topics in antiviral medicine.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Randomisation to week 48(+6)
|
||||||||||||||||||
|
|||||||||||||||||||
Notes [11] - Only performed on young people that reached the primary endpoint. [12] - Only performed on young people that reached the primary endpoint. |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Mean change in CD4% at week 48 from randomisation | ||||||||||||
End point description |
Reporting mean change from the global baseline value (across both arms).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomisation and week 48 visit.
|
||||||||||||
|
|||||||||||||
Notes [13] - All patients with a reading at week 48 and week 0. [14] - All patients with a reading at week 48 and week 0. |
|||||||||||||
Statistical analysis title |
Linear regression | ||||||||||||
Statistical analysis description |
Linear regression of CD4% at week 48, adjusting for randomised arm, baseline CD4% and stratification factors. Presenting mean difference between arms.
|
||||||||||||
Comparison groups |
Continuous therapy v Short Cycle Therapy
|
||||||||||||
Number of subjects included in analysis |
187
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.76 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.2
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.9 | ||||||||||||
upper limit |
1.3 |
|
|||||||||||||
End point title |
Mean change in absolute CD4 count at week 48 from randomisation | ||||||||||||
End point description |
Reporting mean change from the global baseline value (across both arms).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomisation and week 48 visit.
|
||||||||||||
|
|||||||||||||
Notes [15] - All patients with a reading at week 48 and week 0. [16] - All patients with a reading at week 48 and week 0. |
|||||||||||||
Statistical analysis title |
Linear regression. | ||||||||||||
Statistical analysis description |
Linear regression of absolute CD4 count at week 48, adjusting for randomised arm, baseline absolute CD4 count and stratification factors. Presenting mean difference between arms.
|
||||||||||||
Comparison groups |
Continuous therapy v Short Cycle Therapy
|
||||||||||||
Number of subjects included in analysis |
183
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.68 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-12.5
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-71.9 | ||||||||||||
upper limit |
46.9 |
|
|||||||||||||
End point title |
Mean change in Creatinine at week 48 from randomisation | ||||||||||||
End point description |
Reporting mean change from the global baseline value (across both arms).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomisation and week 48 visit.
|
||||||||||||
|
|||||||||||||
Notes [17] - All patients with a reading at week 48 and week 0. [18] - All patients with a reading at week 48 and week 0. |
|||||||||||||
Statistical analysis title |
Linear regression. | ||||||||||||
Statistical analysis description |
Linear regression of creatinine at week 48, adjusting for randomised arm, baseline creatinine and stratification factors. Presenting mean difference between arms.
|
||||||||||||
Comparison groups |
Short Cycle Therapy v Continuous therapy
|
||||||||||||
Number of subjects included in analysis |
183
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.42 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0 | ||||||||||||
upper limit |
0.1 |
|
|||||||||||||
End point title |
Mean change in bilirubin at week 48 from randomisation | ||||||||||||
End point description |
Reporting mean change from the global baseline value (across both arms).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomisation and week 48 visit.
|
||||||||||||
|
|||||||||||||
Notes [19] - All patients with a reading at week 48 and week 0. [20] - All patients with a reading at week 48 and week 0. |
|||||||||||||
Statistical analysis title |
Linear regression. | ||||||||||||
Statistical analysis description |
Linear regression of bilirubin at week 48, adjusting for randomised arm, baseline bilirubin and stratification factors. Presenting mean difference between arms.
|
||||||||||||
Comparison groups |
Continuous therapy v Short Cycle Therapy
|
||||||||||||
Number of subjects included in analysis |
183
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.45 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0 | ||||||||||||
upper limit |
0.1 |
|
|||||||||||||
End point title |
Mean change in Alkaline phosphatase at week 48 from randomisation | ||||||||||||
End point description |
Reporting mean change from the global baseline value (across both arms).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomisation and week 48 visit.
|
||||||||||||
|
|||||||||||||
Notes [21] - All patients with a reading at week 48 and week 0. [22] - All patients with a reading at week 48 and week 0. |
|||||||||||||
Statistical analysis title |
Linear regression. | ||||||||||||
Statistical analysis description |
Linear regression of Alkaline phosphatase at week 48, adjusting for randomised arm, baseline Alkaline phosphatase and stratification factors. Presenting mean difference between arms.
|
||||||||||||
Comparison groups |
Continuous therapy v Short Cycle Therapy
|
||||||||||||
Number of subjects included in analysis |
180
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.77 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-3.7
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-28.3 | ||||||||||||
upper limit |
21 |
|
|||||||||||||
End point title |
Mean change in Aspartate transaminase at week 48 from randomisation | ||||||||||||
End point description |
Reporting mean change from the global baseline value (across both arms).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomisation and week 48 visit.
|
||||||||||||
|
|||||||||||||
Notes [23] - All patients with a reading at week 48 and week 0. [24] - All patients with a reading at week 48 and week 0. |
|||||||||||||
Statistical analysis title |
Linear regression. | ||||||||||||
Statistical analysis description |
Linear regression of aspartate transaminase at week 48, adjusting for randomised arm, baseline aspartate transaminase and stratification factors. Presenting mean difference between arms.
|
||||||||||||
Comparison groups |
Continuous therapy v Short Cycle Therapy
|
||||||||||||
Number of subjects included in analysis |
174
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.22 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-1.7
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-4.4 | ||||||||||||
upper limit |
1 |
|
|||||||||||||
End point title |
Mean change in Alanine transaminase at week 48 from randomisation | ||||||||||||
End point description |
Reporting mean change from the global baseline value (across both arms).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomisation and week 48 visit.
|
||||||||||||
|
|||||||||||||
Notes [25] - All patients with a reading at week 48 and week 0. [26] - All patients with a reading at week 48 and week 0. |
|||||||||||||
Statistical analysis title |
Linear regression. | ||||||||||||
Statistical analysis description |
Linear regression of alanine transaminase at week 48, adjusting for randomised arm, baseline alanine transaminase and stratification factors. Presenting mean difference between arms.
|
||||||||||||
Comparison groups |
Continuous therapy v Short Cycle Therapy
|
||||||||||||
Number of subjects included in analysis |
183
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.23 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-1.7
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-5.8 | ||||||||||||
upper limit |
1.4 |
|
|||||||||||||
End point title |
Mean change in Glucose at week 48 from randomisation | ||||||||||||
End point description |
Reporting mean change from the global baseline value (across both arms).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomisation and week 48 visit.
|
||||||||||||
|
|||||||||||||
Notes [27] - All patients with a reading at week 48 and week 0. [28] - All patients with a reading at week 48 and week 0. |
|||||||||||||
Statistical analysis title |
Linear regression. | ||||||||||||
Statistical analysis description |
Linear regression of glucose at week 48, adjusting for randomised arm, baseline glucose and stratification factors. Presenting mean difference between arms.
|
||||||||||||
Comparison groups |
Continuous therapy v Short Cycle Therapy
|
||||||||||||
Number of subjects included in analysis |
179
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.93 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.1
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-3.3 | ||||||||||||
upper limit |
3 |
|
|||||||||||||
End point title |
Mean change in Triglycerides at week 48 from randomisation | ||||||||||||
End point description |
Reporting mean change from the global baseline value (across both arms).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomisation and week 48 visit.
|
||||||||||||
|
|||||||||||||
Notes [29] - All patients with a reading at week 48 and week 0. [30] - All patients with a reading at week 48 and week 0. |
|||||||||||||
Statistical analysis title |
Linear regression. | ||||||||||||
Statistical analysis description |
Linear regression of triglycerides at week 48, adjusting for randomised arm, baseline triglycerides and stratification factors. Presenting mean difference between arms.
|
||||||||||||
Comparison groups |
Continuous therapy v Short Cycle Therapy
|
||||||||||||
Number of subjects included in analysis |
186
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.2 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
8.8
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-4.7 | ||||||||||||
upper limit |
22.2 |
|
|||||||||||||
End point title |
Mean change in LDL Cholesterol at week 48 from randomisation | ||||||||||||
End point description |
Reporting mean change from the global baseline value (across both arms).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomisation and week 48 visit.
|
||||||||||||
|
|||||||||||||
Notes [31] - All patients with a reading at week 48 and week 0. [32] - All patients with a reading at week 48 and week 0. |
|||||||||||||
Statistical analysis title |
Linear regression. | ||||||||||||
Statistical analysis description |
Linear regression of LDL cholesterol at week 48, adjusting for randomised arm, baseline LDL cholesterol and stratification factors. Presenting mean difference between arms.
|
||||||||||||
Comparison groups |
Continuous therapy v Short Cycle Therapy
|
||||||||||||
Number of subjects included in analysis |
181
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.52 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
1.5
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-3.1 | ||||||||||||
upper limit |
6.1 |
|
|||||||||||||
End point title |
Mean change in VLDL cholesterol at week 48 from randomisation | ||||||||||||
End point description |
Reporting mean change from the global baseline value (across both arms).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomisation and week 48 visit.
|
||||||||||||
|
|||||||||||||
Notes [33] - All patients with a reading at week 48 and week 0. [34] - All patients with a reading at week 48 and week 0. |
|||||||||||||
Statistical analysis title |
Linear regression. | ||||||||||||
Statistical analysis description |
Linear regression of VLDL cholesterol at week 48, adjusting for randomised arm, baseline VLDL cholesterol and stratification factors. Presenting mean difference between arms.
|
||||||||||||
Comparison groups |
Continuous therapy v Short Cycle Therapy
|
||||||||||||
Number of subjects included in analysis |
101
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.44 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-1.2
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-4.3 | ||||||||||||
upper limit |
1.9 |
|
|||||||||||||
End point title |
Mean change in HDL cholesterol at week 48 from randomisation | ||||||||||||
End point description |
Reporting mean change from the global baseline value (across both arms).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomisation and week 48 visit.
|
||||||||||||
|
|||||||||||||
Notes [35] - All patients with a reading at week 48 and week 0. [36] - All patients with a reading at week 48 and week 0. |
|||||||||||||
Statistical analysis title |
Linear regression. | ||||||||||||
Statistical analysis description |
Linear regression of HDL cholesterol at week 48, adjusting for randomised arm, baseline HDL cholesterol and stratification factors. Presenting mean difference between arms.
|
||||||||||||
Comparison groups |
Continuous therapy v Short Cycle Therapy
|
||||||||||||
Number of subjects included in analysis |
184
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.24 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-1.7
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-4.6 | ||||||||||||
upper limit |
1.2 | ||||||||||||
Statistical analysis title |
Linear regression. | ||||||||||||
Statistical analysis description |
Linear regression of HDL cholesterol at week 48, adjusting for randomised arm, baseline HDL cholesterol and stratification factors. Presenting mean difference between arms.
|
||||||||||||
Comparison groups |
Continuous therapy v Short Cycle Therapy
|
||||||||||||
Number of subjects included in analysis |
184
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.28 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-1.6
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-4.5 | ||||||||||||
upper limit |
1.3 |
|
|||||||||||||
End point title |
Mean change in total cholesterol at week 48 from randomisation | ||||||||||||
End point description |
Reporting mean change from the global baseline value (across both arms).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomisation and week 48 visit.
|
||||||||||||
|
|||||||||||||
Notes [37] - All patients with a reading at week 48 and week 0. [38] - All patients with a reading at week 48 and week 0. |
|||||||||||||
Statistical analysis title |
Linear regression. | ||||||||||||
Statistical analysis description |
Linear regression of total cholesterol at week 48, adjusting for randomised arm, baseline total cholesterol and stratification factors. Presenting mean difference between arms.
|
||||||||||||
Comparison groups |
Continuous therapy v Short Cycle Therapy
|
||||||||||||
Number of subjects included in analysis |
186
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.35 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
2.8
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-3 | ||||||||||||
upper limit |
8.5 |
|
|||||||||||||
End point title |
Mean change in Haemoglobin at week 48 from randomisation | ||||||||||||
End point description |
Reporting mean change from the global baseline value (across both arms).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomisation and week 48 visit.
|
||||||||||||
|
|||||||||||||
Notes [39] - All patients with a reading at week 48 and week 0. [40] - All patients with a reading at week 48 and week 0. |
|||||||||||||
Statistical analysis title |
Linear regression. | ||||||||||||
Statistical analysis description |
Linear regression of haemoglobin at week 48, adjusting for randomised arm, baseline haemoglobin and stratification factors. Presenting mean difference between arms.
|
||||||||||||
Comparison groups |
Continuous therapy v Short Cycle Therapy
|
||||||||||||
Number of subjects included in analysis |
189
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.37 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.1
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.2 | ||||||||||||
upper limit |
0.4 |
|
|||||||||||||
End point title |
Mean change in MCV at week 48 from randomisation | ||||||||||||
End point description |
Reporting mean change from the global baseline value (across both arms).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomisation and week 48 visit.
|
||||||||||||
|
|||||||||||||
Notes [41] - All patients with a reading at week 48 and week 0. [42] - All patients with a reading at week 48 and week 0. |
|||||||||||||
Statistical analysis title |
Linear regression. | ||||||||||||
Statistical analysis description |
Linear regression of MCV at week 48, adjusting for randomised arm, baseline MCV and stratification factors. Presenting mean difference between arms.
|
||||||||||||
Comparison groups |
Continuous therapy v Short Cycle Therapy
|
||||||||||||
Number of subjects included in analysis |
187
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
< 0.001 [43] | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-2.1
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-3.5 | ||||||||||||
upper limit |
-0.6 | ||||||||||||
Notes [43] - Significicant difference between arms - higher MCV in the continuous therapy arm. |
|
|||||||||||||
End point title |
Mean change in white blood cell count at week 48 from randomisation | ||||||||||||
End point description |
Reporting mean change from the global baseline value (across both arms).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomisation and week 48 visit.
|
||||||||||||
|
|||||||||||||
Notes [44] - All patients with a reading at week 48 and week 0. [45] - All patients with a reading at week 48 and week 0. |
|||||||||||||
Statistical analysis title |
Linear regression. | ||||||||||||
Statistical analysis description |
Linear regression of white blood cell count at week 48, adjusting for randomised arm, baseline white blood cell count and stratification factors. Presenting mean difference between arms.
|
||||||||||||
Comparison groups |
Continuous therapy v Short Cycle Therapy
|
||||||||||||
Number of subjects included in analysis |
189
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.09 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.3
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.1 | ||||||||||||
upper limit |
0.7 |
|
|||||||||||||
End point title |
Mean change in Lymphocyte count at week 48 from randomisation | ||||||||||||
End point description |
Reporting mean change from the global baseline value (across both arms).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomisation and week 48 visit.
|
||||||||||||
|
|||||||||||||
Notes [46] - All patients with a reading at week 48 and week 0. [47] - All patients with a reading at week 48 and week 0. |
|||||||||||||
Statistical analysis title |
Linear regression. | ||||||||||||
Statistical analysis description |
Linear regression of lymphocyte count at week 48, adjusting for randomised arm, baseline lymphocyte count and stratification factors. Presenting mean difference between arms.
|
||||||||||||
Comparison groups |
Continuous therapy v Short Cycle Therapy
|
||||||||||||
Number of subjects included in analysis |
182
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.34 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.6
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.7 | ||||||||||||
upper limit |
2.1 |
|
|||||||||||||
End point title |
Mean change in Neutrophil count at week 48 from randomisation | ||||||||||||
End point description |
Reporting mean change from the global baseline value (across both arms).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomisation and week 48 visit.
|
||||||||||||
|
|||||||||||||
Notes [48] - All patients with a reading at week 48 and week 0. [49] - All patients with a reading at week 48 and week 0. |
|||||||||||||
Statistical analysis title |
Linear regression. | ||||||||||||
Statistical analysis description |
Linear regression of neutrophil count at week 48, adjusting for randomised arm, baseline neutrophil count and stratification factors. Presenting mean difference between arms.
|
||||||||||||
Comparison groups |
Short Cycle Therapy v Continuous therapy
|
||||||||||||
Number of subjects included in analysis |
182
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.12 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.3
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.1 | ||||||||||||
upper limit |
0.7 |
|
|||||||||||||
End point title |
Mean change in platelet count at week 48 from randomisation | ||||||||||||
End point description |
Reporting mean change from the global baseline value (across both arms).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomisation and week 48 visit.
|
||||||||||||
|
|||||||||||||
Notes [50] - All patients with a reading at week 48 and week 0. [51] - All patients with a reading at week 48 and week 0. |
|||||||||||||
Statistical analysis title |
Linear regression. | ||||||||||||
Statistical analysis description |
Linear regression of platelet count at week 48, adjusting for randomised arm, baseline platelet count and stratification factors. Presenting mean difference between arms.
|
||||||||||||
Comparison groups |
Short Cycle Therapy v Continuous therapy
|
||||||||||||
Number of subjects included in analysis |
189
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.03 [52] | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-20.9
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-39.1 | ||||||||||||
upper limit |
-2.1 | ||||||||||||
Notes [52] - Significant difference between the arms, higher platelet count in the continuous therapy arm. |
|
|||||||||||||||||||
End point title |
Young person questionnaire - how did taking weekends off make things for you? [53] | ||||||||||||||||||
End point description |
This questionnaire was only completed in the SCT arm.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Week 48 assessment/time of switch to continuous therapy/ last main trial visit (if after week 48).
|
||||||||||||||||||
Notes [53] - 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: Acceptability questionnaires only completed by those randomised to SCT. |
|||||||||||||||||||
|
|||||||||||||||||||
Notes [54] - Only answerred by those randomised to SCT arm |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Carer questionnaire - how did stopping meds at weekend make things for the young person? [55] | ||||||||||||||||||
End point description |
This questionnaire was only asked in the SCT arm.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Week 48 assessment/time of switch to continuous therapy/ last main trial visit (if after week 48).
|
||||||||||||||||||
Notes [55] - 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: Acceptability questionnaires only completed by those randomised to SCT. |
|||||||||||||||||||
|
|||||||||||||||||||
Notes [56] - Only answerred by those randomised to the SCT arm. |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Adherence- Missed Doses at Last Visit | ||||||||||||||||||||||||
End point description |
Participants were asked if they missed any doses since the last visit.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Collected at Week 4, 12, 24, 36, and 48.
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Statistical analysis title |
Comparison of missed doses at week 4 | ||||||||||||||||||||||||
Comparison groups |
Short Cycle Therapy v Continuous therapy
|
||||||||||||||||||||||||
Number of subjects included in analysis |
199
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.14 | ||||||||||||||||||||||||
Method |
Fisher exact | ||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
Statistical analysis title |
Comparison of missed doses at week 12 | ||||||||||||||||||||||||
Comparison groups |
Continuous therapy v Short Cycle Therapy
|
||||||||||||||||||||||||
Number of subjects included in analysis |
199
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.593 | ||||||||||||||||||||||||
Method |
Fisher exact | ||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
Statistical analysis title |
Comparison of missed doses at week 24 | ||||||||||||||||||||||||
Comparison groups |
Continuous therapy v Short Cycle Therapy
|
||||||||||||||||||||||||
Number of subjects included in analysis |
199
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.488 | ||||||||||||||||||||||||
Method |
Fisher exact | ||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
Statistical analysis title |
Comparison of missed doses at week 38 | ||||||||||||||||||||||||
Comparison groups |
Continuous therapy v Short Cycle Therapy
|
||||||||||||||||||||||||
Number of subjects included in analysis |
199
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.193 | ||||||||||||||||||||||||
Method |
Fisher exact | ||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
Statistical analysis title |
Comparison of missed doese at week 48 | ||||||||||||||||||||||||
Comparison groups |
Continuous therapy v Short Cycle Therapy
|
||||||||||||||||||||||||
Number of subjects included in analysis |
199
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.854 | ||||||||||||||||||||||||
Method |
Fisher exact | ||||||||||||||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Mean change in CD8% at week 48 from randomisation | ||||||||||||
End point description |
Reporting mean change from the global baseline value (across both arms).
|
||||||||||||
End point type |
Other pre-specified
|
||||||||||||
End point timeframe |
Randomisation and week 48 visit.
|
||||||||||||
|
|||||||||||||
Notes [57] - All patients with a reading at week 48 and week 0. [58] - All patients with a reading at week 48 and week 0. |
|||||||||||||
Statistical analysis title |
Linear regression. | ||||||||||||
Statistical analysis description |
Linear regression of CD8% at week 48, adjusting for randomised arm, baseline CD8% and stratification factors. Presenting mean difference between arms.
|
||||||||||||
Comparison groups |
Continuous therapy v Short Cycle Therapy
|
||||||||||||
Number of subjects included in analysis |
175
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.8 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.2
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1.6 | ||||||||||||
upper limit |
1.2 |
|
|||||||||||||
End point title |
Mean change in absolute CD8 count at week 48 from randomisation | ||||||||||||
End point description |
Reporting mean change from the global baseline value (across both arms).
|
||||||||||||
End point type |
Other pre-specified
|
||||||||||||
End point timeframe |
Randomisation and week 48 visit.
|
||||||||||||
|
|||||||||||||
Notes [59] - All patients with a reading at week 48 and week 0. [60] - All patients with a reading at week 48 and week 0. |
|||||||||||||
Statistical analysis title |
Linear regression. | ||||||||||||
Statistical analysis description |
Linear regression of absolute CD8 count at week 48, adjusting for randomised arm, baseline absolute CD8 count and stratification factors. Presenting mean difference between arms.
|
||||||||||||
Comparison groups |
Continuous therapy v Short Cycle Therapy
|
||||||||||||
Number of subjects included in analysis |
175
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.85 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-6.4
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-74.5 | ||||||||||||
upper limit |
61.7 |
|
|||||||||||||
End point title |
Mean change in CD3% at week 48 from randomisation | ||||||||||||
End point description |
Reporting mean change from the global baseline value (across both arms).
|
||||||||||||
End point type |
Other pre-specified
|
||||||||||||
End point timeframe |
Randomisation and week 48 visit.
|
||||||||||||
|
|||||||||||||
Notes [61] - All patients with a reading at week 48 and week 0. [62] - All patients with a reading at week 48 and week 0. |
|||||||||||||
Statistical analysis title |
Linear regression. | ||||||||||||
Statistical analysis description |
Linear regression of CD3% at week 48, adjusting for randomised arm, baseline CD3% and stratification factors. Presenting mean difference between arms.
|
||||||||||||
Comparison groups |
Short Cycle Therapy v Continuous therapy
|
||||||||||||
Number of subjects included in analysis |
174
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.99 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1.9 | ||||||||||||
upper limit |
1.9 |
|
|||||||||||||
End point title |
Mean change in absolute CD3 count at week 48 from randomisation | ||||||||||||
End point description |
Reporting mean change from the global baseline value (across both arms).
|
||||||||||||
End point type |
Other pre-specified
|
||||||||||||
End point timeframe |
Randomisation and week 48 visit.
|
||||||||||||
|
|||||||||||||
Notes [63] - All patients with a reading at week 48 and week 0. [64] - All patients with a reading at week 48 and week 0. |
|||||||||||||
Statistical analysis title |
Linear regression. | ||||||||||||
Statistical analysis description |
Linear regression of absolute CD3 count at week 48, adjusting for randomised arm, baseline absolute CD3 count and stratification factors. Presenting mean difference between arms.
|
||||||||||||
Comparison groups |
Continuous therapy v Short Cycle Therapy
|
||||||||||||
Number of subjects included in analysis |
174
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.72 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-25.5
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-163.7 | ||||||||||||
upper limit |
112.7 |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Randomisation to 54 weeks after randomisation.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
For non-serious adverse events we reported grade three or four adverse clinical or laboratory adverse events.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Continuous therapy
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Patients randomised to continuing their ART strategy, taking ART every day. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Short Cycle Therapy
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Patients take their ART as normal for 5 days a week, with a break at the weekends, taking no ART for 2 days every week. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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01 Apr 2014 |
The TSC recommended that the participants are followed for 2 years after completion of the main trial (long term follow up). |
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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. | |||
None reported |