search
Back to results

Efficacy of Cyclophosphamide Versus Methylprednisolone in Patients With Secondary Progressive Multiple Sclerosis (PROMESS)

Primary Purpose

Multiple Sclerosis, Chronic Progressive

Status
Completed
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Cyclophosphamide (drug)
Methylprednisolone (drug)
Sponsored by
University Hospital, Bordeaux
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Sclerosis, Chronic Progressive focused on measuring Multiple Sclerosis, Chronic Progressive, Cyclophosphamide, Methylprednisolone, Randomized Controlled Trials, Double-Blind Study

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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 Exclusion Criteria: 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) Psychosis Current or past (< 3 months) participation in another drug trial Prior use of cyclophosphamide, lymphoid irradiation, monoclonal antibodies anti CD4 or anti CD52 or anti-VLA-4 therapies, cladribine ou cyclosporine A Other clinical types of MS : Secondary progressive phase evolving for more than 4 years ; Remittent type of MS without progression between relapses ; Primary progressive type of MS Use of interferon beta, methotrexate or imurel in the month prior to study. Treatment with intravenous monthly corticoids in the year prior to study. Treatment with corticoids (3 to 5 days) in the 2 month prior to study.

Sites / Locations

  • CH de la Cote Basque
  • CHU Besançon
  • Hôpital Pellegrin, Département de neurologie
  • CHU Caen
  • Hôpital Gabriel Montpied
  • AP HP Henri Mondor
  • CHU Dijon
  • CHU Lille Hôpital Salengro
  • CHU Limoges
  • GHICL Hôpital St. Philibert
  • (CHU Lyon) Hôpital neurologique
  • Hôpital La Timone
  • (CHR Metz-Thionville) Hôpital Notre Dame de Bon Secours
  • (CHU Montpellier), Hôpital de Gui de Chauliac
  • CHU Nancy Hôpital central
  • Hôpital Guillaume et René Laënnec
  • CHU Nice Hôpital Pasteur
  • (CHU Nîmes) Hôpital Caremeau
  • Fondation Rothschild
  • (AP HP) Hôpital Tenon
  • Centre Hospitalier de Pau
  • CHU de POISSY
  • (CHU Reims) Hôpital Robert Debré
  • CHU Ponchaillou
  • CH d'Angoulême Girac
  • (CHRU Starsbourg) Hôpital civil

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

1

2

Arm Description

Cyclophosphamide

Methylprednisolone

Outcomes

Primary Outcome Measures

Delay to disability deterioration as assessed by the Expanded Disability Status Scale (EDSS: 0.5 or 1 point increase, depending on baseline score)

Secondary Outcome Measures

Proportion of patients with disability deterioration (EDSS: 0.5 or 1 point increase, depending on baseline score)
Multiple Sclerosis Functional Composite (MSFC) and the Z scores of MSFC three components
Number of MS relapses
Proportion of patients with adverse events and delay of occurrence of adverse events
Quality of life questionnaires
Disability self-assessment questionnaires

Full Information

First Posted
October 17, 2005
Last Updated
March 14, 2012
Sponsor
University Hospital, Bordeaux
Collaborators
Ministry of Health, France
search

1. Study Identification

Unique Protocol Identification Number
NCT00241254
Brief Title
Efficacy of Cyclophosphamide Versus Methylprednisolone in Patients With Secondary Progressive Multiple Sclerosis
Acronym
PROMESS
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2012
Overall Recruitment Status
Completed
Study Start Date
December 2005 (undefined)
Primary Completion Date
March 2010 (Actual)
Study Completion Date
March 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Bordeaux
Collaborators
Ministry of Health, France

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
Background 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. A slight efficacy of Methylprednisolone has been reported in this indication. Objectives The primary objective is to evaluate the efficacy of IV cyclophosphamide on the prevention of disability deterioration in patients with secondary progressive multiple sclerosis. The secondary objectives are to evaluate safety, tolerability and efficacy of IV cyclophosphamide on the Multiple Sclerosis Functional Composite (MSFC) and the number of relapses. Study design Randomized double-blind two-arm controlled trial. Intervention Experimental group : 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. Outcomes Primary outcome : delay to disability deterioration as assessed by the Expanded Disability Status Scale (EDSS: 0.5 or 1 point increase, depending on baseline score) evaluated every 4 weeks for one year, then every 8 weeks for one year. Secondary outcomes : proportion of patients with disability deterioration (EDSS: 0.5 or 1 point increase, depending on baseline score), Multiple Sclerosis Functional Composite (MSFC) and the Z scores of MSFC three components, number of MS relapses, proportion of patients with adverse events and delay of occurrence of adverse events, quality of life questionnaires. Quality of life questionnaires Disability self-assessment questionnaires Main time of assessment : 2 years. Sample size 360 patients Statistical analysis Intention-to-treat analysis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis, Chronic Progressive
Keywords
Multiple Sclerosis, Chronic Progressive, Cyclophosphamide, Methylprednisolone, Randomized Controlled Trials, Double-Blind Study

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
138 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
Cyclophosphamide
Arm Title
2
Arm Type
Active Comparator
Arm Description
Methylprednisolone
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide (drug)
Intervention Description
IV cyclophosphamide infusion administered every 4 weeks during 1 year and every 8 weeks during 1 year.
Intervention Type
Drug
Intervention Name(s)
Methylprednisolone (drug)
Intervention Description
Control group : IV methylprednisolone infusion administered every 4 weeks during 1 year and every 8 weeks during 1 year.
Primary Outcome Measure Information:
Title
Delay to disability deterioration as assessed by the Expanded Disability Status Scale (EDSS: 0.5 or 1 point increase, depending on baseline score)
Time Frame
every 4 weeks for one year, then every 8 weeks for one year
Secondary Outcome Measure Information:
Title
Proportion of patients with disability deterioration (EDSS: 0.5 or 1 point increase, depending on baseline score)
Time Frame
every month during one year then every two months during the 2nd year
Title
Multiple Sclerosis Functional Composite (MSFC) and the Z scores of MSFC three components
Time Frame
Visit number 1, 2, 13(at one year),19 (at two years) and 20 (last visit)
Title
Number of MS relapses
Time Frame
all along the follow up period
Title
Proportion of patients with adverse events and delay of occurrence of adverse events
Time Frame
all along the follow up period
Title
Quality of life questionnaires
Time Frame
visit 2, 13(at one year) and 19 (at two years)
Title
Disability self-assessment questionnaires
Time Frame
visite 2, 13 et 19

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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) Psychosis Current or past (< 3 months) participation in another drug trial Prior use of cyclophosphamide, lymphoid irradiation, monoclonal antibodies anti CD4 or anti CD52 or anti-VLA-4 therapies, cladribine ou cyclosporine A Other clinical types of MS : Secondary progressive phase evolving for more than 4 years ; Remittent type of MS without progression between relapses ; Primary progressive type of MS Use of interferon beta, methotrexate or imurel in the month prior to study. Treatment with intravenous monthly corticoids in the year prior to study. Treatment with corticoids (3 to 5 days) in the 2 month prior to study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bruno Brochet, Professor
Organizational Affiliation
University Hospital, Bordeaux, France
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Paul Perez, Dr
Organizational Affiliation
University Hospital, Bordeaux, France
Official's Role
Study Chair
Facility Information:
Facility Name
CH de la Cote Basque
City
Bayonne
ZIP/Postal Code
64109
Country
France
Facility Name
CHU Besançon
City
Besançon
ZIP/Postal Code
25030
Country
France
Facility Name
Hôpital Pellegrin, Département de neurologie
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
CHU Caen
City
Caen
ZIP/Postal Code
14033
Country
France
Facility Name
Hôpital Gabriel Montpied
City
Clermont Ferrand
ZIP/Postal Code
63003
Country
France
Facility Name
AP HP Henri Mondor
City
Créteil
ZIP/Postal Code
94010
Country
France
Facility Name
CHU Dijon
City
Dijon
ZIP/Postal Code
21033
Country
France
Facility Name
CHU Lille Hôpital Salengro
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
CHU Limoges
City
Limoges
ZIP/Postal Code
87042
Country
France
Facility Name
GHICL Hôpital St. Philibert
City
Lomme
ZIP/Postal Code
59462
Country
France
Facility Name
(CHU Lyon) Hôpital neurologique
City
Lyon
ZIP/Postal Code
69394
Country
France
Facility Name
Hôpital La Timone
City
Marseille
ZIP/Postal Code
13385
Country
France
Facility Name
(CHR Metz-Thionville) Hôpital Notre Dame de Bon Secours
City
Metz
ZIP/Postal Code
57038
Country
France
Facility Name
(CHU Montpellier), Hôpital de Gui de Chauliac
City
Montpellier
ZIP/Postal Code
34295
Country
France
Facility Name
CHU Nancy Hôpital central
City
Nancy
ZIP/Postal Code
54035
Country
France
Facility Name
Hôpital Guillaume et René Laënnec
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
CHU Nice Hôpital Pasteur
City
Nice
ZIP/Postal Code
06002
Country
France
Facility Name
(CHU Nîmes) Hôpital Caremeau
City
Nîmes
ZIP/Postal Code
30029
Country
France
Facility Name
Fondation Rothschild
City
Paris
ZIP/Postal Code
75019
Country
France
Facility Name
(AP HP) Hôpital Tenon
City
Paris
ZIP/Postal Code
75970
Country
France
Facility Name
Centre Hospitalier de Pau
City
Pau
ZIP/Postal Code
64046
Country
France
Facility Name
CHU de POISSY
City
Poissy
ZIP/Postal Code
78300
Country
France
Facility Name
(CHU Reims) Hôpital Robert Debré
City
Reims
ZIP/Postal Code
51092
Country
France
Facility Name
CHU Ponchaillou
City
Rennes
ZIP/Postal Code
35033
Country
France
Facility Name
CH d'Angoulême Girac
City
Saint Michel
ZIP/Postal Code
16470
Country
France
Facility Name
(CHRU Starsbourg) Hôpital civil
City
Strasbourg
ZIP/Postal Code
67091
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
28045953
Citation
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.
Results Reference
derived

Learn more about this trial

Efficacy of Cyclophosphamide Versus Methylprednisolone in Patients With Secondary Progressive Multiple Sclerosis

We'll reach out to this number within 24 hrs