Outcome of Acquired Haemophilia With Steroid Combined With Cyclophosphamide Versus Steroid Combined With Rituximab (CREHA Study) (CREHA)

March 19, 2026 updated by: University Hospital, Rouen
CREHA project is a study comparing steroid combined with cyclophosphamide versus steroid combined with rituximab in patients with acquired haemophilia. The study will test the hypothesis that steroid combined with cyclophosphamide is more effective than steroid plus rituximab for FVIII inhibitor eradication in acquired haemophilia.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

CREHA project is a multicenter, randomized, controlled efficacity and safety study comparing steroid combined with cyclophosphamide versus steroid combined with rituximab in patients with acquired haemophilia. The study will test the hypothesis that steroid combined with cyclophosphamide is more effective than steroid plus rituximab for FVIII inhibitor eradication in acquired haemophilia

Study Type

Interventional

Enrollment (Actual)

110

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Amiens, France, 80054
        • University Hospital Amiens
      • Bondy, France, 93140
        • Hospital Jean Verdier
      • Boulogne-Billancourt, France, 92104
        • Hospital Ambroise Paré
      • Brest, France, 29609
        • University Hospital of Brest - Hospital La cavale Blanche
      • Béziers, France, 34525
        • Hospital of Béziers
      • Caen, France, 14033
        • University Hospital Côte de Nacre
      • Clermont-Ferrand, France, 63003
        • University Hospital G. Montpied
      • Créteil, France, 94010
        • Hospital Henri Mondor
      • Dijon, France, 21033
        • University Hospital of Dijon - Hospital Général
      • Dijon, France, 21079
        • University Hospital Bocage
      • Grenoble, France, 38043
        • University Hospital Michallon
      • Le Kremlin-Bicêtre, France, 94270
        • Hospital Kremlin-Bicêtre
      • Lille, France, 59037
        • University Regional Hospital of Lille
      • Limoges, France, 87042
        • University Hospital of Limoges
      • Marseille, France, 13385
        • AP-HM, University Hospital La Conception
      • Montpellier, France, 34295
        • University Hospital Saint-Eloi
      • Nancy, France
        • Regional Center of Haemophilia Treatment (CRTH) de Lorraine
      • Nantes, France, 44093
        • University Hospital of Nantes, Hospital Hôtel-Dieu
      • Nice, France, 06202
        • Hospital Archet 1
      • Paris, France, 75018
        • Hospital Bichat
      • Paris, France, 75651
        • Hospital Pitié-Salpêtrière
      • Paris, France, 75475
        • Hospital Saint-Louis
      • Paris, France, 75679
        • Hospital Cochin
      • Paris, France, 75908
        • Europen Hospital of Georges Pompidou (HEGP)
      • Pessac, France, 33604
        • University Hospital of Bordeaux - Hospital Haut-Lévêque
      • Pierre-Bénite, France, 69495
        • Hospital Lyon Sud
      • Poitiers, France, 86021
        • University hospital of Poitiers
      • Rennes, France, 35000
        • Hospital Sud / Hospital Pontchaillou
      • Rouen, France, 76031
        • University Hospital of Rouen
      • Saint-Etienne, France, 42055
        • Hospital Nord
      • Strasbourg, France, 67098
        • University Regional Hospital Hautepierre
      • Toulouse, France, 31059
        • Hospital Purpan
      • Toulouse, France, 31059
        • Hospital Rangueil
      • Tours, France, 37044
        • Hopsital Bretonneau

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • men or women
  • women post-menpausal or with ongoing contraception
  • 18 years old or more
  • diagnosis of acquired hemophilia
  • patient must be insured
  • patient has provided written informed consent prior to enrolment
  • patient compliant

Exclusion Criteria:

  • constitutional hemophilia
  • chemotherapy
  • ongoing treatment with prednisone > 20mg further more 1 month
  • ongoing treatment with prednisone >0.7 mg/d further more 10 days
  • thrombocytopenia
  • leukopenia
  • chronic disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Bras A
Steroid 1mg/kg/d and Cyclophosphamide 2mg/kg/d
Drug: Steroid + cyclophosphamide
Experimental: Bras B
Steroid 1mg/kg/d and Rituximab 375 mg/m2 every week during four weeks
Drug: Steroid + rituximab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary objective
Time Frame: During 18 months
Demonstrate the inferiority of steroid combined with rituximab as compared to the recommended immunosuppressive approach (steroid combined with cysclophosphamide for 21 to 42 days) as the first-line immunosuppressive therapy for FVIII inhibitor eradication in acquired haemophilia
During 18 months
Primary efficacy outcome
Time Frame: During 18 months
The primary efficacy outcome is the proportion of patients achieving complete remission defined as titer FVII inhibitor lower than 0.4 Bethesda unit and factor VIII level > 50%
During 18 months
Primary safety outcomes
Time Frame: During 18 months
The primary safety outcomes will be the occurrence of major bleeding and infection related immunosuppressive treatment adverse events.
During 18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Secondary objective
Time Frame: 6 months, 12 months and 18 months
Secondary objective are time to complete remission, number of relapse at M6, M12, M18, adverse events (especially related to bleeding or to immunosuppressive treatment) and mortality
6 months, 12 months and 18 months
Other key safety outcome
Time Frame: During 18 months
The other key safety outcome are clinically relevant non major bleeding, diabetes and mortality non-related with acquired haemophilia or immunosuppressive therapy
During 18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Rouen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2012

Primary Completion (Actual)

January 14, 2021

Study Completion (Actual)

January 14, 2021

Study Registration Dates

First Submitted

October 16, 2012

First Submitted That Met QC Criteria

March 8, 2013

First Posted (Estimated)

March 11, 2013

Study Record Updates

Last Update Posted (Actual)

March 24, 2026

Last Update Submitted That Met QC Criteria

March 19, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2011/090/HP
  • 2011-003539-68 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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