Efficacy of Cyclophosphamide Versus Methylprednisolone in Patients With Secondary Progressive Multiple Sclerosis
PROMESS
A Double-blind, Two-arm, Multicenter, Randomized Trial to Evaluate Efficacy of Cyclophosphamide Versus Methylprednisolone in Patients With Recent Secondary Progressive Multiple Sclerosis: P.R.OM.E.S.S Study
2 other identifiers
interventional
138
1 country
26
Brief Summary
Preliminary not-controlled clinical studies of the efficacy of monthly intravenous cyclophosphamide administration in secondary progressive multiple sclerosis reported encouraging results, but no randomized controlled trial has been conducted so far. The primary objective of this trial is to evaluate the efficacy of IV cyclophosphamide as compared to IV methylprednisolone administered every 4 weeks during 1 year and every 8 weeks during 1 year, on the delay to confirmed disability deterioration as assessed by the Expanded Disability Status Scale (EDSS) in patients with secondary progressive multiple sclerosis. The secondary objectives are to evaluate safety, tolerability and efficacy at 2 years on the Multiple Sclerosis Functional Composite (MSFC), the percentage of patients with disability deterioration (EDSS) and the number of relapses. An intention-to-treat statistical analysis will be carried out.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Dec 2005
Longer than P75 for phase_3
26 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 17, 2005
CompletedFirst Posted
Study publicly available on registry
October 18, 2005
CompletedStudy Start
First participant enrolled
December 1, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2010
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2012
CompletedMarch 15, 2012
March 1, 2012
4.2 years
October 17, 2005
March 14, 2012
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Delay to disability deterioration as assessed by the Expanded Disability Status Scale (EDSS: 0.5 or 1 point increase, depending on baseline score)
every 4 weeks for one year, then every 8 weeks for one year
Secondary Outcomes (6)
Proportion of patients with disability deterioration (EDSS: 0.5 or 1 point increase, depending on baseline score)
every month during one year then every two months during the 2nd year
Multiple Sclerosis Functional Composite (MSFC) and the Z scores of MSFC three components
Visit number 1, 2, 13(at one year),19 (at two years) and 20 (last visit)
Number of MS relapses
all along the follow up period
Proportion of patients with adverse events and delay of occurrence of adverse events
all along the follow up period
Quality of life questionnaires
visit 2, 13(at one year) and 19 (at two years)
- +1 more secondary outcomes
Study Arms (2)
1
EXPERIMENTALCyclophosphamide
2
ACTIVE COMPARATORMethylprednisolone
Interventions
IV cyclophosphamide infusion administered every 4 weeks during 1 year and every 8 weeks during 1 year.
Control group : IV methylprednisolone infusion administered every 4 weeks during 1 year and every 8 weeks during 1 year.
Eligibility Criteria
You may qualify if:
- Multiple sclerosis (MS) subjects (Mc Donald et al criteria),
- Aged 18 to 65
- Diagnosis of secondary progressive MS ( Lublin and Reingold criteria)
- Progressive deterioration phase of at least 6 months and less than 4 years.
- Reduction of walking capacity and increase EDSS not ascribed to consequence of relapses (at least 0.5 point) in the last 12 months
- EDSS between 4.0 and 6.5 included
- Female participating must use contraceptives while on study drug
- Written informed consent
- Patient protected by French social security system
You may not qualify if:
- Others diseases interfering with MS or treatment
- Recent history (within the previous 2 years) of drug or alcohol abuse.
- Patients with psychiatric illnesses who are unable to provide written, informed consent prior to any testing under this protocol
- Hemorrhagic cystitis
- Pregnant or lactating women
- Known allergy at cyclophosphamide, corticoids and in particular methylprednisolone
- Persistent infectious diseases
- Patients with bladder permanent catheterization
- Known history of cardiac arrhythmia after methylprednisolone intravenous treatment
- Abnormal screening/baseline blood tests exceeding any of the limits defined below : Hb \< 9g/dl or Total white blood cell count less than 3 000/mm3 or lymphocytes count less than 900/ mm3 or Platelet count less than 125 000/mm3
- Gastric or duodenal ulcer in evolution
- Gut diverticulosis
- Diabetes mellitus
- Known history of active hepatitis (ASAT \>3 X ULN)
- Known history of renal failure (creatinine level \> 180 µmol/L)
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University Hospital, Bordeauxlead
- Ministry of Health, Francecollaborator
Study Sites (26)
CH de la Cote Basque
Bayonne, 64109, France
CHU Besançon
Besançon, 25030, France
Hôpital Pellegrin, Département de neurologie
Bordeaux, 33076, France
CHU Caen
Caen, 14033, France
Hôpital Gabriel Montpied
Clermont-Ferrand, 63003, France
AP HP Henri Mondor
Créteil, 94010, France
CHU Dijon
Dijon, 21033, France
CHU Lille Hôpital Salengro
Lille, 59037, France
CHU Limoges
Limoges, 87042, France
GHICL Hôpital St. Philibert
Lomme, 59462, France
(CHU Lyon) Hôpital neurologique
Lyon, 69394, France
Hôpital La Timone
Marseille, 13385, France
(CHR Metz-Thionville) Hôpital Notre Dame de Bon Secours
Metz, 57038, France
(CHU Montpellier), Hôpital de Gui de Chauliac
Montpellier, 34295, France
CHU Nancy Hôpital central
Nancy, 54035, France
Hôpital Guillaume et René Laënnec
Nantes, 44093, France
CHU Nice Hôpital Pasteur
Nice, 06002, France
(CHU Nîmes) Hôpital Caremeau
Nîmes, 30029, France
Fondation Rothschild
Paris, 75019, France
(AP HP) Hôpital Tenon
Paris, 75970, France
Centre Hospitalier de Pau
Pau, 64046, France
CHU de POISSY
Poissy, 78300, France
(CHU Reims) Hôpital Robert Debré
Reims, 51092, France
CHU Ponchaillou
Rennes, 35033, France
CH d'Angoulême Girac
Saint-Michel, 16470, France
(CHRU Starsbourg) Hôpital civil
Strasbourg, 67091, France
Related Publications (1)
Brochet B, Deloire MS, Perez P, Loock T, Baschet L, Debouverie M, Pittion S, Ouallet JC, Clavelou P, de Seze J, Collongues N, Vermersch P, Zephir H, Castelnovo G, Labauge P, Lebrun C, Cohen M, Ruet A; PROMESS study investigators. Double-Blind Controlled Randomized Trial of Cyclophosphamide versus Methylprednisolone in Secondary Progressive Multiple Sclerosis. PLoS One. 2017 Jan 3;12(1):e0168834. doi: 10.1371/journal.pone.0168834. eCollection 2017.
PMID: 28045953DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Bruno Brochet, Professor
University Hospital, Bordeaux, France
- STUDY CHAIR
Paul Perez, Dr
University Hospital, Bordeaux, France
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 17, 2005
First Posted
October 18, 2005
Study Start
December 1, 2005
Primary Completion
March 1, 2010
Study Completion
March 1, 2012
Last Updated
March 15, 2012
Record last verified: 2012-03