Outcome of Acquired Haemophilia With Steroid Combined With Cyclophosphamide Versus Steroid Combined With Rituximab (CREHA Study)
CREHA
2 other identifiers
interventional
110
1 country
34
Brief Summary
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.
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 May 2012
Longer than P75 for phase_3
34 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
Study Start
First participant enrolled
May 1, 2012
CompletedFirst Submitted
Initial submission to the registry
October 16, 2012
CompletedFirst Posted
Study publicly available on registry
March 11, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 14, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
January 14, 2021
CompletedMarch 24, 2026
March 1, 2026
8.7 years
October 16, 2012
March 19, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Primary objective
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
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
The primary safety outcomes will be the occurrence of major bleeding and infection related immunosuppressive treatment adverse events.
During 18 months
Secondary Outcomes (2)
Secondary objective
6 months, 12 months and 18 months
Other key safety outcome
During 18 months
Study Arms (2)
Bras A
ACTIVE COMPARATORSteroid 1mg/kg/d and Cyclophosphamide 2mg/kg/d
Bras B
EXPERIMENTALSteroid 1mg/kg/d and Rituximab 375 mg/m2 every week during four weeks
Interventions
Eligibility Criteria
You may qualify if:
- men or women
- women post-menpausal or with ongoing contraception
- years old or more
- diagnosis of acquired hemophilia
- patient must be insured
- patient has provided written informed consent prior to enrolment
- patient compliant
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (34)
University Hospital Amiens
Amiens, 80054, France
Hospital of Béziers
Béziers, 34525, France
Hospital Jean Verdier
Bondy, 93140, France
Hospital Ambroise Paré
Boulogne-Billancourt, 92104, France
University Hospital of Brest - Hospital La cavale Blanche
Brest, 29609, France
University Hospital Côte de Nacre
Caen, 14033, France
University Hospital G. Montpied
Clermont-Ferrand, 63003, France
Hospital Henri Mondor
Créteil, 94010, France
University Hospital of Dijon - Hospital Général
Dijon, 21033, France
University Hospital Bocage
Dijon, 21079, France
University Hospital Michallon
Grenoble, 38043, France
Hospital Kremlin-Bicêtre
Le Kremlin-Bicêtre, 94270, France
University Regional Hospital of Lille
Lille, 59037, France
university Hospital of Limoges
Limoges, 87042, France
AP-HM, University Hospital La Conception
Marseille, 13385, France
University Hospital Saint-Eloi
Montpellier, 34295, France
Regional Center of Haemophilia Treatment (CRTH) de Lorraine
Nancy, France
University Hospital of Nantes, Hospital Hôtel-Dieu
Nantes, 44093, France
Hospital Archet 1
Nice, 06202, France
Hospital Bichat
Paris, 75018, France
Hospital Saint-Louis
Paris, 75475, France
Hospital Pitié-Salpêtrière
Paris, 75651, France
Hospital Cochin
Paris, 75679, France
Europen Hospital of Georges Pompidou (HEGP)
Paris, 75908, France
University Hospital of Bordeaux - Hospital Haut-Lévêque
Pessac, 33604, France
Hospital Lyon Sud
Pierre-Bénite, 69495, France
University Hospital of Poitiers
Poitiers, 86021, France
Hospital Sud / Hospital Pontchaillou
Rennes, 35000, France
University Hospital of Rouen
Rouen, 76031, France
Hospital Nord
Saint-Etienne, 42055, France
University Regional Hospital Hautepierre
Strasbourg, 67098, France
Hospital Purpan
Toulouse, 31059, France
Hospital Rangueil
Toulouse, 31059, France
Hopsital Bretonneau
Tours, 37044, France
Related Publications (1)
Levesque H, Viallard JF, Houivet E, Bonnotte B, Voisin S, Le Cam-Duchez V, Maillot F, Lambert M, Liozon E, Hervier B, Fain O, Guillet B, Schmidt J, Luca LE, Ebbo M, Ferreira-Maldent N, Babuty A, Sailler L, Duffau P, Barbay V, Audia S, Benichou J, Graveleau J, Benhamou Y; CREHA Study investigators on behalf the scientific committee of the "Societe Nationale Francaise de Medecine Interne" (SNFMI - French National Society of Internal Medicine). Cyclophosphamide vs rituximab for eradicating inhibitors in acquired hemophilia A: A randomized trial in 108 patients. Thromb Res. 2024 May;237:79-87. doi: 10.1016/j.thromres.2024.03.012. Epub 2024 Mar 15.
PMID: 38555718DERIVED
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 16, 2012
First Posted
March 11, 2013
Study Start
May 1, 2012
Primary Completion
January 14, 2021
Study Completion
January 14, 2021
Last Updated
March 24, 2026
Record last verified: 2026-03