Acquired HaemophiliaPhase 3CREHANCT01808911
Outcome of Acquired Haemophilia With Steroid Combined With Cyclophosphamide Versus Steroid Combined With Rituximab (CREHA Study)
A Phase 3 study testing Steroid + cyclophosphamide and Steroid + rituximab in people with Acquired Haemophilia, run by University Hospital, Rouen at 34 sites in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acquired Haemophilia
- What is being tested?
- Steroid + cyclophosphamide and Steroid + rituximab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 34 sitesFrance
- Study dates
- May 2012to 14 Jan 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
34 sites in 1 country.
34 sites in 1 country
France34 sites
University Hospital Amiens
Amiens, 80054
Hospital of Béziers
Béziers, 34525
Hospital Jean Verdier
Bondy, 93140
Hospital Ambroise Paré
Boulogne-Billancourt, 92104
University Hospital of Brest - Hospital La cavale Blanche
Brest, 29609
University Hospital Côte de Nacre
Caen, 14033
University Hospital G. Montpied
Clermont-Ferrand, 63003
Hospital Henri Mondor
Créteil, 94010
University Hospital of Dijon - Hospital Général
Dijon, 21033
University Hospital Bocage
Dijon, 21079
University Hospital Michallon
Grenoble, 38043
Hospital Kremlin-Bicêtre
Le Kremlin-Bicêtre, 94270
University Regional Hospital of Lille
Lille, 59037
university Hospital of Limoges
Limoges, 87042
AP-HM, University Hospital La Conception
Marseille, 13385
University Hospital Saint-Eloi
Montpellier, 34295
Regional Center of Haemophilia Treatment (CRTH) de Lorraine
Nancy
University Hospital of Nantes, Hospital Hôtel-Dieu
Nantes, 44093
Hospital Archet 1
Nice, 06202
Hospital Bichat
Paris, 75018
Hospital Saint-Louis
Paris, 75475
Hospital Pitié-Salpêtrière
Paris, 75651
Hospital Cochin
Paris, 75679
Europen Hospital of Georges Pompidou (HEGP)
Paris, 75908
University Hospital of Bordeaux - Hospital Haut-Lévêque
Pessac, 33604
Hospital Lyon Sud
Pierre-Bénite, 69495
University Hospital of Poitiers
Poitiers, 86021
Hospital Sud / Hospital Pontchaillou
Rennes, 35000
University Hospital of Rouen
Rouen, 76031
Hospital Nord
Saint-Etienne, 42055
University Regional Hospital Hautepierre
Strasbourg, 67098
Hospital Purpan
Toulouse, 31059
Hospital Rangueil
Toulouse, 31059
Hopsital Bretonneau
Tours, 37044
About this study
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.
Read the 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
- Conditions
- Acquired Haemophilia
- Being tested
- Steroid + cyclophosphamide, Steroid + rituximab
- Keywords
- Acquired haemophilia, Comparative and randomized study, Cyclophosphamide, Rituximab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Steroid + cyclophosphamideDrug
Steroid + rituximabDrug
| Study group | Role | What they receive |
|---|---|---|
| Bras A | Active comparator | Steroid 1mg/kg/d and Cyclophosphamide 2mg/kg/d Receives: Drug: Steroid + cyclophosphamide |
| Bras B | Experimental | Steroid 1mg/kg/d and Rituximab 375 mg/m2 every week during four weeks Receives: Drug: Steroid + rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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%
Measured: During 18 months
Primary safety outcomes
The primary safety outcomes will be the occurrence of major bleeding and infection related immunosuppressive treatment adverse events.
Measured: During 18 months
Secondary outcomes (2)
Secondary objective
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
Measured: 6 months, 12 months and 18 months
Other key safety outcome
The other key safety outcome are clinically relevant non major bleeding, diabetes and mortality non-related with acquired haemophilia or immunosuppressive therapy
Measured: During 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2013 (estimated)
- Study startMay 2012
- Primary completion14 Jan 2021
- Study completion14 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acquired HaemophiliaStudies of the same condition, open and under way.
- More trials run by University Hospital, RouenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Enrolment
- 110 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Rouen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01808911
- Sponsor's protocol ID
- 2011/090/HP
- Other IDs
- 2011-003539-68
- Acronym
- CREHA
- Status last verified
- Mar 2026
- First submitted
- 16 Oct 2012
- Last updated
- 24 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 38555718
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Outcome of Acquired Haemophilia With Steroid Combined With Cyclophosphamide Versus Steroid Combined With Rituximab (CREHA Study)
- ClinicalTrials.gov ID
- NCT01808911
- Acronym / sponsor ID
- CREHA / 2011/090/HP
- Conditions
- Acquired Haemophilia
- Keywords
- Acquired haemophilia, Comparative and randomized study, Cyclophosphamide, Rituximab
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 110 participants (actual)
- Lead sponsor
- University Hospital, RouenUniversity, hospital or other
- Study start
- May 2012 (actual)
- Primary completion
- 14 Jan 2021 (actual)
- Study completion
- 14 Jan 2021 (actual)
- First posted
- 11 Mar 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bras A | Active comparator | Drug: Steroid + cyclophosphamideSteroid 1mg/kg/d and Cyclophosphamide 2mg/kg/d |
| Bras B | Experimental | Drug: Steroid + rituximabSteroid 1mg/kg/d and Rituximab 375 mg/m2 every week during four weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- men or women
- women post-menpausal or with ongoing contraception
- 18 years old or more
- diagnosis of acquired hemophilia
- patient must be insured
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Steroid + cyclophosphamide | Drug | Bras A |
| Steroid + rituximab | Drug | Bras B |
Primary outcome
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
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%
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.
2 secondary outcomes
Secondary objective
Time frame: 6 months, 12 months and 18 months
Other key safety outcome
Time frame: During 18 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2026.
- Derived from this study: PubMed 38555718Levesque 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
34 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Steroid + cyclophosphamide and Steroid + rituximab in people with Acquired Haemophilia, run by University Hospital, Rouen at 34 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 34 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary objective (time frame: During 18 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01808911, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2026.