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

14 de marzo de 2012 actualizado por: University Hospital, Bordeaux

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

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.

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Descripción detallada

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.

Tipo de estudio

Intervencionista

Inscripción (Actual)

138

Fase

  • Fase 3

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

  • Francia
      • Bayonne, Francia, 64109
        • CH de la Côte Basque
      • Besançon, Francia, 25030
        • CHU Besançon
      • Bordeaux, Francia, 33076
        • Hôpital Pellegrin, Département de neurologie
      • Caen, Francia, 14033
        • CHU caen
      • Clermont Ferrand, Francia, 63003
        • Hôpital Gabriel Montpied
      • Créteil, Francia, 94010
        • AP HP Henri Mondor
      • Dijon, Francia, 21033
        • CHU Dijon
      • Lille, Francia, 59037
        • CHU Lille Hôpital Salengro
      • Limoges, Francia, 87042
        • CHU Limoges
      • Lomme, Francia, 59462
        • GHICL Hôpital St. Philibert
      • Lyon, Francia, 69394
        • (CHU Lyon) Hôpital neurologique
      • Marseille, Francia, 13385
        • Hôpital La Timone
      • Metz, Francia, 57038
        • (CHR Metz-Thionville) Hôpital Notre Dame de Bon Secours
      • Montpellier, Francia, 34295
        • (CHU Montpellier), Hôpital de Gui de Chauliac
      • Nancy, Francia, 54035
        • CHU Nancy Hôpital Central
      • Nantes, Francia, 44093
        • Hopital Guillaume Et Rene Laennec
      • Nice, Francia, 06002
        • CHU Nice Hôpital Pasteur
      • Nîmes, Francia, 30029
        • (CHU Nîmes) Hôpital Caremeau
      • Paris, Francia, 75019
        • Fondation Rothschild
      • Paris, Francia, 75970
        • (AP HP) Hôpital Tenon
      • Pau, Francia, 64046
        • Centre Hospitalier de Pau
      • Poissy, Francia, 78300
        • CHU de Poissy
      • Reims, Francia, 51092
        • (CHU Reims) Hôpital Robert Debré
      • Rennes, Francia, 35033
        • Chu Ponchaillou
      • Saint Michel, Francia, 16470
        • CH d'Angoulême Girac
      • Strasbourg, Francia, 67091
        • (CHRU Starsbourg) Hôpital civil

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años a 65 años (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

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.

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Doble

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: 1
Ciclofosfamida
Droga: Cyclophosphamide (drug)
IV cyclophosphamide infusion administered every 4 weeks during 1 year and every 8 weeks during 1 year.
Comparador activo: 2
Methylprednisolone
Droga: Methylprednisolone (drug)
Control group : IV methylprednisolone infusion administered every 4 weeks during 1 year and every 8 weeks during 1 year.

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Periodo de tiempo
Delay to disability deterioration as assessed by the Expanded Disability Status Scale (EDSS: 0.5 or 1 point increase, depending on baseline score)
Periodo de tiempo: every 4 weeks for one year, then every 8 weeks for one year
every 4 weeks for one year, then every 8 weeks for one year

Medidas de resultado secundarias

Medida de resultado
Periodo de tiempo
Proportion of patients with disability deterioration (EDSS: 0.5 or 1 point increase, depending on baseline score)
Periodo de tiempo: every month during one year then every two months during the 2nd year
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
Periodo de tiempo: Visit number 1, 2, 13(at one year),19 (at two years) and 20 (last visit)
Visit number 1, 2, 13(at one year),19 (at two years) and 20 (last visit)
Number of MS relapses
Periodo de tiempo: all along the follow up period
all along the follow up period
Proportion of patients with adverse events and delay of occurrence of adverse events
Periodo de tiempo: all along the follow up period
all along the follow up period
Quality of life questionnaires
Periodo de tiempo: visit 2, 13(at one year) and 19 (at two years)
visit 2, 13(at one year) and 19 (at two years)
Disability self-assessment questionnaires
Periodo de tiempo: visite 2, 13 et 19
visite 2, 13 et 19

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

University Hospital, Bordeaux

Colaboradores

Ministry of Health, France

Investigadores

  • Investigador principal: Bruno Brochet, Professor, University Hospital, Bordeaux, France

Publicaciones y enlaces útiles

La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.

Publicaciones Generales

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio

1 de diciembre de 2005

Finalización primaria (Actual)

1 de marzo de 2010

Finalización del estudio (Actual)

1 de marzo de 2012

Fechas de registro del estudio

Enviado por primera vez

17 de octubre de 2005

Primero enviado que cumplió con los criterios de control de calidad

17 de octubre de 2005

Publicado por primera vez (Estimar)

18 de octubre de 2005

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

15 de marzo de 2012

Última actualización enviada que cumplió con los criterios de control de calidad

14 de marzo de 2012

Última verificación

1 de marzo de 2012

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • 9408-04
  • 2004-005

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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