Rendu Osler DiseasePhase 3BABHNCT03227263
BABH Study: Efficacy and Safety of Bevacizumab on Severe Bleedings Associated With Hemorrhagic Hereditary Telangiectasia (HHT).
A Phase 3 study testing Bevacizumab and sodium chloride 0.9% in people with Rendu Osler Disease and Telangiectasia, Hereditary Hemorrhagic, run by Hospices Civils de Lyon at 4 sites in France.
Trial summary
The recognized manifestations of HHT are all due to abnormalities of vascular structure. Epistaxis and digestive arteriovenous malformations may be responsible for severe hemorrhages in 5% of HHT patients, requiring repeated blood transfusions and are associated with high morbidity. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rendu Osler Disease, Telangiectasia, Hereditary Hemorrhagic
- What is being tested?
- Bevacizumab and sodium chloride 0.9%
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 4 sitesFrance
- Study dates
- 28 Sep 2017to 15 May 2020
- 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
- Age ≥ 18 years.
- Patients who have given their free informed and signed consent.
- Patients affiliated to a social security scheme or similar.
- Patients monitored for clinically confirmed HHT (presence of at least three Curaçao criteria) and / or with molecular biology confirmation.
- Blood transfusions with the requirement for at least 4 units of blood in the 3-month period before study enrollment, related to epistaxis or digestive bleeding.
Who cannot join
- Women who are pregnant or nursing (lactating), women of child-bearing potential without reliable contraception during the treatment and for at least 6 months after the last dose.
- Patients who are protected adults under the terms of the law (French Public Health Code).
- Refusal to consent.
- Patients for whom the diagnosis of HHT has not been confirmed clinically and / or by molecular biology study.
- Active infection and/or fever>38°C
- Participation in another clinical trial within 28 days prior to inclusion.
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- Hypersensitivity to the active substance or to any of the excipients.
- Known hypersensitivity to products of Chinese hamster ovary cells (CHO) or other recombinant human or humanized antibodies.
- Patients who have taken Avastin ® intravenously in the 6 months prior to inclusion.
- Patients who have had a therapeutic endoscopy for gastrointestinal bleeding or ENT surgery for epistaxis will have to wait at least 3 months less after treatment to be included if bleeding persists.
- Patients who had a surgery in the month prior inclusion or planned surgery within 6 months
- Severe peripheral arterial disease with ulcerations
- Unhealed wound
- Thrombosis in the 6 months prior to inclusion
- Anticoagulant treatment
- Uncontrolled high blood pressure
Trial locations and contacts
4 sites in 1 country.
France4 sites
CHU d'Angers
Angers
Hôpital Ambroise Paré
Boulogne-Billancourt
Hôpital Femme Mère Enfant
Bron
CHU de Montpellier Hôpital St Eloi
Montpellier
About this study
Official title: BABH Study: Efficacy and Safety of Bevacizumab on Severe Bleedings Associated With Hemorrhagic Hereditary Telangiectasia (HHT). A National, Multicenter Phase III Study
The recognized manifestations of HHT are all due to abnormalities of vascular structure. Epistaxis and digestive arteriovenous malformations may be responsible for severe hemorrhages in 5% of HHT patients, requiring repeated blood transfusions and are associated with high morbidity. There is currently no standard and efficient management of this severe symptom. It is also well known that HHT-associated hemorrhages have the greatest negative impact on quality of life among HHT patients, and is responsible for anemia, blood transfusions, hospitalizations, depressive syndrome and a high psycho-social impact.
Since 2006, it has been suggested by animal models and then by clinical reports that anti-VEGF therapy may be useful to treat HHT. 4 case reports have been published on efficacy of intravenous bevacizumab, a humanized monoclonal antibody in HHT on severe hemorrhages.
Read more
Intravenous bevacizumab has been used in a previous clinical trial to measure efficacy and tolerance of this drug in HHT patients with severe liver involvement. Furthermore, a reduction was observed in the duration of the nosebleeds after treatment and was encouraging to treat bleeding. We completed this study by a pharmacokinetic-pharmacodynamic (PK-PD) model in order to assess the individual concentration-effect relationship of bevacizumab.
However, no randomized prospective study has been performed and published to evaluate the efficacy in this indication. A total of 24 patients will be randomized versus placebo in a multicenter phase III trial. The Avastin or placebo will be infused at 5mg/kg every 14 days with a total of 6 cures with a 3 months following period.
- Being tested
- Bevacizumab, sodium chloride 0.9%
- Keywords
- Hereditary Hemorrhagic Telangiectasia (HHT), VEGF therapy, Bevacizumab
- Medical subject headings
- Telangiectasia, Hereditary Hemorrhagic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Bevacizumab (Avastin®) concentrate at 25mg/mL is diluted at 5 mg/kg for infusion every 14 days for 6 consecutive administrations
sodium chloride 0.9%Drug
0.9% of sodium chloride is infused every 14 days for 6 consecutive administrations
| Study group | Role | What they receive |
|---|---|---|
| Bevacizumab | Experimental | Intravenous infusion of Bevacizumab at a dose of 5 mg/kg Receives: Drug: Bevacizumab |
| Placebo | Placebo comparator | 0.9% of sodium chloride is infused every 14 days for 6 consecutive administrations Receives: Drug: sodium chloride 0.9% |
What is being measured
The primary outcome is the main question the study is designed to answer.
number of red blood cell transfusions
Measured: 6 months
Secondary outcomes (12)
hemoglobin
The relative evolution in hemoglobin level at 3 months after the beginning of the treatment is compared to the value measured at inclusion
Measured: 3 months
hemoglobin
The relative evolution in hemoglobin level at 6 months after the beginning of the treatment is compared to the value measured at inclusion
Measured: 6 months
epistaxis frequency
Comparison of an average over a 3-month period before and after the treatment.
Measured: 3 months before treatment up to 6 months from the inclusion
duration of nosebleeds
Comparison of an average over a 3-month period before and after the treatment.
Measured: 3 months before treatment up to 6 months from the inclusion
digestive vascular malformations
Comparison of digestive endoscopy before and after treatment if gastrointestinal bleeding have already externalized before treatment
Measured: 6 months
quality of life (SF36).
Comparison of SF36 questionnaire before and after treatment.
Measured: 3 months
quality of life (SF36).
Comparison of SF36 questionnaire before and after treatment.
Measured: 6 months
severity epistaxis score (ESS).
Comparison of ESS questionnaire before and after treatment
Measured: 3 months
severity epistaxis score (ESS).
Comparison of ESS questionnaire before and after treatment
Measured: 6 months.
To evaluate pharmacokinetics of bevacizumab dose
Description of bevacizumab serum concentrations over time, the relationship between bevacizumab concentrations and adverse events and clinical/biological endpoints
Measured: Before each 6 infusions
To evaluate pharmacokinetics of bevacizumab dose
Description of bevacizumab serum concentrations over time, the relationship between bevacizumab concentrations and adverse events and clinical/biological endpoints
Measured: 2 hours after the first treatment infusion
adverse events
To assess the safety of bevacizumab.Tolerance will be evaluated by recording adverse events and by clinical examinations during the treatment period and the follow up period.
Measured: up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2017
- Study start28 Sep 2017
- Primary completion15 May 2020
- Study completion15 May 2020
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 Rendu Osler DiseaseStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe 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
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- DUPUIS-GIROD, MD, Principal investigator, Hospices Civils de Lyon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03227263
- Sponsor's protocol ID
- 69HCL17_0018
- Other IDs
- 2017-001031-39, 2017
- Acronym
- BABH
- Status last verified
- Jun 2020
- First submitted
- 21 Jul 2017
- Last updated
- 6 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Dupuis-Girod S, Riviere S, Lavigne C, Fargeton AE, Gilbert-Dussardier B, Grobost V, Leguy-Seguin V, Maillard H, Mohamed S, Decullier E, Roux A, Bernard L, Saurin JC, Saroul N, Faure F, Cartier C, Altwegg R, Laccourreye L, Oberti F, Beaudoin M, Dhelens C, Desvignes C, Azzopardi N, Paintaud G, Hermann R, Chinet T. Efficacy and safety of intravenous bevacizumab on severe bleeding associated with hemorrhagic hereditary telangiectasia: A national, randomized multicenter trial. J Intern Med. 2023 Dec;294(6):761-774. doi: 10.1111/joim.13714. Epub 2023 Aug 23.
PubMed 37592715
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- BABH Study: Efficacy and Safety of Bevacizumab on Severe Bleedings Associated With Hemorrhagic Hereditary Telangiectasia (HHT). A National, Multicenter Phase III Study
- ClinicalTrials.gov ID
- NCT03227263
- Acronym / sponsor ID
- BABH / 69HCL17_0018
- Keywords
- Hereditary Hemorrhagic Telangiectasia (HHT), VEGF therapy, Bevacizumab
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 28 Sep 2017 (actual)
- Primary completion
- 15 May 2020 (actual)
- Study completion
- 15 May 2020 (actual)
- First posted
- 24 Jul 2017 (actual)
- 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.
The recognized manifestations of HHT are all due to abnormalities of vascular structure. Epistaxis and digestive arteriovenous malformations may be responsible for severe hemorrhages in 5% of HHT patients, requiring repeated blood transfusions and are associated with high morbidity. There is currently no standard and efficient management of this severe symptom. It is also well known that HHT-associated hemorrhages have the greatest negative impact on quality of life among HHT patients, and is responsible for anemia, blood transfusions, hospitalizations, depressive syndrome and a high psycho-social impact.
Since 2006, it has been suggested by animal models and then by clinical reports that anti-VEGF therapy may be useful to treat HHT. 4 case reports have been published on efficacy of intravenous bevacizumab, a humanized monoclonal antibody in HHT on severe hemorrhages.
Intravenous bevacizumab has been used in a previous clinical trial to measure efficacy and tolerance of this drug in HHT patients with severe liver involvement. Furthermore, a reduction was observed in the duration of the nosebleeds after treatment and was encouraging to treat bleeding. We completed this study by a pharmacokinetic-pharmacodynamic (PK-PD) model in order to assess the individual concentration-effect relationship of bevacizumab.
However, no randomized prospective study has been performed and published to evaluate the efficacy in this indication. A total of 24 patients will be randomized versus placebo in a multicenter phase III trial. The Avastin or placebo will be infused at 5mg/kg every 14 days with a total of 6 cures with a 3 months following period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab | Experimental | Drug: BevacizumabIntravenous infusion of Bevacizumab at a dose of 5 mg/kg |
| Placebo | Placebo comparator | Drug: sodium chloride 0.9%0.9% of sodium chloride is infused every 14 days for 6 consecutive administrations |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age ≥ 18 years.
- Patients who have given their free informed and signed consent.
- Patients affiliated to a social security scheme or similar.
- Patients monitored for clinically confirmed HHT (presence of at least three Curaçao criteria) and / or with molecular biology confirmation.
- Blood transfusions with the requirement for at least 4 units of blood in the 3-month period before study enrollment, related to epistaxis or digestive bleeding.
Key exclusion criteria (16 listed)
- Women who are pregnant or nursing (lactating), women of child-bearing potential without reliable contraception during the treatment and for at least 6 months after the last dose.
- Patients who are protected adults under the terms of the law (French Public Health Code).
- Refusal to consent.
- Patients for whom the diagnosis of HHT has not been confirmed clinically and / or by molecular biology study.
- Active infection and/or fever>38°C
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 |
|---|---|---|
| BevacizumabBevacizumab (Avastin®) concentrate at 25mg/mL is diluted at 5 mg/kg for infusion every 14 days for 6 consecutive administrations | Drug | Bevacizumab |
| sodium chloride 0.9%0.9% of sodium chloride is infused every 14 days for 6 consecutive administrations | Drug | Placebo |
Primary outcome
number of red blood cell transfusions
Time frame: 6 months
12 secondary outcomes
hemoglobin
Time frame: 3 months
hemoglobin
Time frame: 6 months
epistaxis frequency
Time frame: 3 months before treatment up to 6 months from the inclusion
duration of nosebleeds
Time frame: 3 months before treatment up to 6 months from the inclusion
digestive vascular malformations
Time frame: 6 months
quality of life (SF36).
Time frame: 3 months
quality of life (SF36).
Time frame: 6 months
severity epistaxis score (ESS).
Time frame: 3 months
severity epistaxis score (ESS).
Time frame: 6 months.
To evaluate pharmacokinetics of bevacizumab dose
Time frame: Before each 6 infusions
To evaluate pharmacokinetics of bevacizumab dose
Time frame: 2 hours after the first treatment infusion
adverse events
Time frame: up to 6 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 6 Aug 2025.
- Results publication: PubMed 37592715Dupuis-Girod S, Riviere S, Lavigne C, Fargeton AE, Gilbert-Dussardier B, Grobost V, Leguy-Seguin V, Maillard H, Mohamed S, Decullier E, Roux A, Bernard L, Saurin JC, Saroul N, Faure F, Cartier C, Altwegg R, Laccourreye L, Oberti F, Beaudoin M, Dhelens C, Desvignes C, Azzopardi N, Paintaud G, Hermann R, Chinet T. Efficacy and safety of intravenous bevacizumab on severe bleeding associated with hemorrhagic hereditary telangiectasia: A national, randomized multicenter trial. J Intern Med. 2023 Dec;294(6):761-774. doi: 10.1111/joim.13714. Epub 2023 Aug 23.
- Individual participant dataSharing planned: No
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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.
DUPUIS-GIROD, MD principal investigator
Hospices Civils de Lyon
4 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 Bevacizumab and sodium chloride 0.9% in people with Rendu Osler Disease and Telangiectasia, Hereditary Hemorrhagic, run by Hospices Civils de Lyon at 4 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 5 inclusion and 16 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 6 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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. Some participants in this study may receive a placebo. 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?
number of red blood cell transfusions (time frame: 6 months). 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 NCT03227263, 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 6 Aug 2025.