BABH Study: Efficacy and Safety of Bevacizumab on Severe Bleedings Associated With Hemorrhagic Hereditary Telangiectasia (HHT). (BABH)

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.

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 Overview

• Status: Completed
• Conditions: Telangiectasia, Hereditary Hemorrhagic; Rendu Osler Disease
• Intervention / Treatment: Drug: Bevacizumab; Drug: sodium chloride 0.9%

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Angers, France
    • CHU d'Angers
  • Boulogne Billancourt, France
    • Hôpital Ambroise Paré
  • Bron, France
    • Hôpital Femme Mère Enfant
  • Montpellier, France
    • CHU de Montpellier Hôpital St Eloi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.
• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bevacizumab; Intravenous infusion of Bevacizumab at a dose of 5 mg/kg	Drug: Bevacizumab; Bevacizumab (Avastin®) concentrate at 25mg/mL is diluted at 5 mg/kg for infusion every 14 days for 6 consecutive administrations
Placebo Comparator: Placebo; 0.9% of sodium chloride is infused every 14 days for 6 consecutive administrations	Drug: sodium chloride 0.9%; 0.9% of sodium chloride is infused every 14 days for 6 consecutive administrations

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
number of red blood cell transfusions	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
hemoglobin	The relative evolution in hemoglobin level at 3 months after the beginning of the treatment is compared to the value measured at inclusion	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	6 months
epistaxis frequency	Comparison of an average over a 3-month period before and after the treatment.	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.	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	6 months
quality of life (SF36).	Comparison of SF36 questionnaire before and after treatment.	3 months
quality of life (SF36).	Comparison of SF36 questionnaire before and after treatment.	6 months
severity epistaxis score (ESS).	Comparison of ESS questionnaire before and after treatment	3 months
severity epistaxis score (ESS).	Comparison of ESS questionnaire before and after treatment	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	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	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.	up to 6 months

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: DUPUIS-GIROD, MD, Hospices Civils de Lyon

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2017
• Primary Completion (Actual): May 15, 2020
• Study Completion (Actual): May 15, 2020

Study Registration Dates

• First Submitted: July 21, 2017
• First Submitted That Met QC Criteria: July 21, 2017
• First Posted (Actual): July 24, 2017

Study Record Updates

• Last Update Posted (Actual): August 6, 2025
• Last Update Submitted That Met QC Criteria: August 1, 2025
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Bevacizumab; Hereditary Hemorrhagic Telangiectasia (HHT); VEGF therapy
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hematologic Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Hemostatic Disorders; Hemorrhagic Disorders; Vascular Malformations; Telangiectasis; Telangiectasia, Hereditary Hemorrhagic; Antineoplastic Agents, Immunological; Antineoplastic Agents; Physiological Effects of Drugs; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: 69HCL17_0018; 2017-001031-39 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No