Clinical Trial Results:
Evaluation de l'efficacité d'une corticothérapie à faible dose, associée à l'acide mycophénolique (Myfortic) dans le traitement d'attaque du syndrome néphrotique à lésions glomérulaires minimes de l'adulte. Etude MSN
Evaluation of Low Dose Corticosteroids Efficiency, Associated With Myfortic ® in the Treatment of Nephrotic Syndrome (MSN)
Summary
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EudraCT number |
2009-011170-15 |
Trial protocol |
FR |
Global end of trial date |
10 Nov 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
26 Jun 2022
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First version publication date |
26 Jun 2022
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Other versions |
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 |
P071226
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01197040 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS
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Sponsor organisation address |
4 Avenue Victoria, PARIS, France, 75004
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Public contact |
Dr Philippe REMY, ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS / Hôpital Henri MONDOR, +33 (0)1 49 81 24 59, philippe.remy@aphp.fr
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Scientific contact |
Dr Philippe REMY, ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS / Hôpital Henri MONDOR, +33 (0)1 49 81 24 59, philippe.remy@aphp.fr
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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 |
05 Dec 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
28 Jul 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
10 Nov 2015
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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 |
L'objectif principal est de comparer le taux de rémission complète à 4 semaines, obtenu sous corticoïdes seuls à pleine dose, 1mg/kg/j, par rapport au groupe sous l'association faible dose de corticoïdes 0,5 mg/kg/j et Myfortic® à la dose de 1440 mg/j.
evaluate efficacy of low dose steroid combined with mycophenolic acid (Myfortic) versus high dose steroid, at 4 weeks, in inducing remission in adults with minimal change nephrotic syndrome (MCNS)
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Protection of trial subjects |
The study was carried out in accordance with the Declaration of Helsinki and the International Conference on Harmonization of Good Clinical Practice.The trial protocol was approved by the institutional review board (Comité de Protection des Personnes Ilede-France II # 2009-04-02.). Written informed consent was obtained from all patients.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
12 Nov 2009
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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 |
France: 117
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Worldwide total number of subjects |
117
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EEA total number of subjects |
117
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
100
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From 65 to 84 years |
16
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85 years and over |
1
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Recruitment
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Recruitment details |
Between November 2009 and June 2014, 117 patients met the inclusion criteria for this study | ||||||||||||||||||||||||
Pre-assignment
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Screening details |
minimal change nephrotic syndrome in adults (MCNS) was based on appropriate renal biopsy examination | ||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall trail (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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Experimental | ||||||||||||||||||||||||
Arm description |
Association of low dose corticosteroids 0.5 mg/kg/day and Myfortic ® at a dose of 1440 mg/day. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
mycophenolate sodium
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Gastro-resistant tablet
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Routes of administration |
Oral use
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Dosage and administration details |
enteric-coated mycophenolate sodium 720 mg twice daily for 24 weeks
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Investigational medicinal product name |
prednisone
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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 |
Prednisone (0.5 mg/kg/day, maximum 40 mg/day) for 24 weeks
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Arm title
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Active Comparator | ||||||||||||||||||||||||
Arm description |
Monotherapy: treatment with only corticosteroids at doses usually 1 mg/kg/day,following a plan of reduction based on the degree of remission. | ||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||
Investigational medicinal product name |
Prednisone
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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 |
oral prednisone (1 mg/kg/day, maximum 80 mg/day) for 24 weeks
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Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: 1 Consent withdrawal before randimazation, thus Excluded (n = 1) |
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Baseline characteristics reporting groups
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Reporting group title |
Experimental
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Reporting group description |
Association of low dose corticosteroids 0.5 mg/kg/day and Myfortic ® at a dose of 1440 mg/day. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Active Comparator
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Reporting group description |
Monotherapy: treatment with only corticosteroids at doses usually 1 mg/kg/day,following a plan of reduction based on the degree of remission. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Experimental
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Reporting group description |
Association of low dose corticosteroids 0.5 mg/kg/day and Myfortic ® at a dose of 1440 mg/day. | ||
Reporting group title |
Active Comparator
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Reporting group description |
Monotherapy: treatment with only corticosteroids at doses usually 1 mg/kg/day,following a plan of reduction based on the degree of remission. |
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End point title |
Complete Remission rate after 4 weeks of treatment | |||||||||
End point description |
The primary endpoint was the complete remission (CR) rate after 4 weeks of treatment.
Complete remission was defined as urine protein-to-creatinine ratio (UPCR) < 30 mg/mmol or trace or negative results on repeat urine albumin dipstick tests, associated with an albumin level > 30 g/l.
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End point type |
Primary
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End point timeframe |
4 weeks
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Notes [1] - Analysis according to the intent-to-treat principle after imputation of missing data. |
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Statistical analysis title |
Primary outcome, Week 4 Complete remission, ITT | |||||||||
Statistical analysis description |
Analysis according to the intent-to-treat principle after imputation of missing data. A multiple imputation approach was used for
handling missing data and limits attrition bias. We used the multiple multivariate imputation by chained equations procedure with the
missing at random assumption. We used both baseline covariates and outcome to impute the missing data values, and we independently
analyzed 20 copies of the data.
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Comparison groups |
Experimental v Active Comparator
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Number of subjects included in analysis |
114
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.44 | |||||||||
Method |
Chi-squared | |||||||||
Parameter type |
Risk ratio (RR) | |||||||||
Point estimate |
1.12
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.84 | |||||||||
upper limit |
1.5 |
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Adverse events information
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Timeframe for reporting adverse events |
Patients were followed up for 1 year after randomization (week 52). They attended follow-up visits every 2 weeks during the first 8 weeks after randomization, and then every 4 weeks until week 24, with a final visit at week 52.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
12.1
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Reporting groups
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Reporting group title |
Experimental
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Reporting group description |
Association of low dose corticosteroids 0.5 mg/kg/day and Myfortic ® at a dose of 1440 mg/day. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Active Comparator
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Reporting group description |
Monotherapy: treatment with only corticosteroids at doses usually 1 mg/kg/day,following a plan of reduction based on the degree of remission. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0.01% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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19 Nov 2009 |
MS1
1 Exclusion criteria modification; addition of fasting blood glucose assay at D1 ; modification of visit partial examination ;
2 New investigation sites added; principal investigator modification at Troyes Hospital |
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14 Dec 2009 |
MS2
Principal investigator modification at Necker Hospital (Paris, 75, France) |
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07 Jun 2010 |
MS3
Visit organisation modification; 1 inclusion criteria and 2 exclusion criteria modification; modification of forbidden drugs and treatment during protocol ; modification of synoptic table ; 3 investigation sites added |
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02 Aug 2010 |
MS4
Investigation site added |
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11 Mar 2013 |
MS5
Inclusion period extension (+6 months) |
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16 Dec 2013 |
MS6
Inclusion period extension (+12months) ; number of subjects needed decreased |
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02 Feb 2015 |
MS7 Inclusion period extension ; number of patients justified |
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09 Nov 2015 |
MS8
Principal investigator modification in 3 investigation sites ; declaration of number of patients included |
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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 | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/30385039 |