Clinical Trial Results:
A randomised clinical trial of mycophenolate mofetil versus cyclophosphamide for remission induction in ANCA associated vasculitis
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Summary
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EudraCT number |
2006-001663-33 |
Trial protocol |
GB CZ ES SE DE IT AT FR |
Global end of trial date |
14 Feb 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
08 Jul 2016
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First version publication date |
30 Jul 2015
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Other versions |
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Summary report(s) |
MYCYC serious adverse events |
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 |
MYCYC
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00414128 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
NA: NA | ||
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Sponsors
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Sponsor organisation name |
Cambridge University Hospitals NHS Foundation Trust
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Sponsor organisation address |
Hills Road, Cambridge, United Kingdom, CB2 0QQ
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Public contact |
David Jayne, Addenbrooke's Hospital
, +44 1223 217159, dj106@cam.ac.uk
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Scientific contact |
David Jayne, Addenbrooke's Hospital
, +44 1223 217159, dj106@cam.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 |
Final
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Date of interim/final analysis |
28 Feb 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
14 Feb 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
14 Feb 2013
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The aim of this trial was to investigate whether a mycophenolate mofetil based induction regimen is as effective as a cyclophosphamide based induction regimen in the treatment of active ANCA associated vasculitis.
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Protection of trial subjects |
All patients were provided with a patient information sheet and provided written informed consent and were free to withdraw from the trial at any point without giving a reason. Patient confidentiality was respected according to national regulations and data was coded before computer entry to maintain confidentiality. Blood samples were coded before being sent to Addenbrooke's Hospital. Study follow up and blood tests were arranged to coincide with standard hospital appointments to avoid additional hospital visits and blood tests as much as possible. According to the trial protocol, patients who did not respond to their assigned treatment regimen, could be withdrawn from trial protocol and treated with additional therapies as required.
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Background therapy |
All patients in this trial received oral glucocorticoids. Glucocorticoid starting dose was 1mg/kg/day reducing down gradually to 5mg per day at the end of month 9 for adults and 0.05-0.075mg/kg/day for patients under the age of 17 years and to continue at this dose until study end at 18 months. | ||
Evidence for comparator |
Cyclophosphamide is the 'gold standard' treatment for remission induction in ANCA vasculitis. It was introduced as a therapy for ANCA vasculitis in 1970 and is associated with remission rates of 70-90% and one year survival rates of 80-90% (survival prior to the introduction of cyclophosphamide was 20%). | ||
Actual start date of recruitment |
12 Mar 2007
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety, Efficacy | ||
Long term follow-up duration |
100 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: 18
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Country: Number of subjects enrolled |
Sweden: 8
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Country: Number of subjects enrolled |
United Kingdom: 73
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Country: Number of subjects enrolled |
Australia: 13
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Country: Number of subjects enrolled |
Belgium: 14
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Country: Number of subjects enrolled |
Czech Republic: 4
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Country: Number of subjects enrolled |
Italy: 8
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Country: Number of subjects enrolled |
New Zealand: 2
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Worldwide total number of subjects |
140
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EEA total number of subjects |
125
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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) |
8
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Adults (18-64 years) |
86
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From 65 to 84 years |
42
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85 years and over |
3
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Recruitment
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Recruitment details |
Patient were recruited from outpatient clinics and on medical wards. The study was open to recruitment of adults from 31-Jan-2007, with paediatric inclusion from 31-Jul-2007. Last patient was recruited on 29-Jul-2011. | |||||||||
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Pre-assignment
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Screening details |
All patients were locally screened for eligibility. Randomisation forms were sent to the central site for all patients who were considered eligible by local sites. A total of 154 patients were screened and put forward for randomisation, 14 were excluded (6 did not meet inclusion criteria, 8 declined to participate) and 140 patients were randomise | |||||||||
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Period 1
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Period 1 title |
Recruitment period (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 |
NA
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Cyclophosphamide | |||||||||
Arm description |
Control | |||||||||
Arm type |
Control | |||||||||
Investigational medicinal product name |
Cyclophosphamide
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Investigational medicinal product code |
5,00911E+15
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Other name |
ACT code L01AA01, CAS 50180
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Pharmaceutical forms |
Powder for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
Per day dose, based on weight, age and renal function, 10 doses of a maximum of 1.2g
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Arm title
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Mycophenolate mofetil | |||||||||
Arm description |
Test | |||||||||
Arm type |
Test | |||||||||
Investigational medicinal product name |
Cellcept (mycophenolate mofetil)
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Investigational medicinal product code |
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Other name |
MA number EU/1/96/005/002, ACT code L04AA06, CAS 128794-94-5
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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 twice daily. Maximum dose 300mg total per day.
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Baseline characteristics reporting groups
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Reporting group title |
Cyclophosphamide
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Reporting group description |
Control | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Mycophenolate mofetil
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Reporting group description |
Test | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Cyclophosphamide
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Reporting group description |
Control | ||
Reporting group title |
Mycophenolate mofetil
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Reporting group description |
Test | ||
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End point title |
Absolute Risk Reduction - ARR (90% Confidence Interval) | |||||||||
End point description |
Number of patients that achieved remission by six months
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End point type |
Primary
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End point timeframe |
Remission by six months
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Statistical analysis title |
ITT | |||||||||
Statistical analysis description |
ITT
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Comparison groups |
Cyclophosphamide v Mycophenolate mofetil
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Number of subjects included in analysis |
140
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [1] | |||||||||
P-value |
< 0.05 | |||||||||
Method |
Absolute Risk Difference | |||||||||
Parameter type |
Risk difference (RD) | |||||||||
Point estimate |
0.057
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Confidence interval |
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level |
90% | |||||||||
sides |
1-sided
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lower limit |
-0.073 | |||||||||
upper limit |
- | |||||||||
| Notes [1] - The non-inferiority margin is an absolute risk difference of 12% for remission outcomes |
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Adverse events information [1]
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Timeframe for reporting adverse events |
Serious adverse events reported to trial management committee within 24 hours of occurrence followed by subsequent reporting to the MHRA according to MHRA criteria.
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Assessment type |
Systematic | ||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||
Dictionary version |
10
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| Frequency threshold for reporting non-serious adverse events: 0% | |||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Please see the attachment for the serious adverse events. The non-serious adverse events have not yet been analysed. |
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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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25 Jun 2007 |
Substantial ammendement to adult protocol (Version 2A) for changes requested by MHRA- drug blood monitoring and changes to mycophenolate mofetil regimen, three additional exclusion criteria added
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26 Nov 2007 |
Substantial ammendement for paediatric protocol (Version 2P) to MHRA for inclusion of children
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04 Apr 2008 |
Substantial ammendment for paediatric protocol (Version 3P) changes to paediatric dosing in protocol to allow MCRN study adoption
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21 Jun 2011 |
Substantial ammendment for adult protocol (Version 3A) PIS and consent forms (Version 4) for updated safety information
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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 | |||
