NCT03227263

Brief 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. 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
24

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Sep 2017

Typical duration for phase_3

Geographic Reach
1 country

4 active sites

Status
completed

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

First Submitted

Initial submission to the registry

July 21, 2017

Completed
3 days until next milestone

First Posted

Study publicly available on registry

July 24, 2017

Completed
2 months until next milestone

Study Start

First participant enrolled

September 28, 2017

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 15, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 15, 2020

Completed
Last Updated

August 6, 2025

Status Verified

June 1, 2020

Enrollment Period

2.6 years

First QC Date

July 21, 2017

Last Update Submit

August 1, 2025

Conditions

Rendu Osler DiseaseTelangiectasia, Hereditary Hemorrhagic

Keywords

Hereditary Hemorrhagic Telangiectasia (HHT)VEGF therapyBevacizumab

Outcome Measures

Primary Outcomes (1)

  • number of red blood cell transfusions

    6 months

Secondary Outcomes (12)

  • hemoglobin

    3 months

  • hemoglobin

    6 months

  • epistaxis frequency

    3 months before treatment up to 6 months from the inclusion

  • duration of nosebleeds

    3 months before treatment up to 6 months from the inclusion

  • digestive vascular malformations

    6 months

  • +7 more secondary outcomes

Study Arms (2)

Bevacizumab

EXPERIMENTAL

Intravenous infusion of Bevacizumab at a dose of 5 mg/kg

Drug: Bevacizumab

Placebo

PLACEBO COMPARATOR

0.9% of sodium chloride is infused every 14 days for 6 consecutive administrations

Drug: sodium chloride 0.9%

Interventions

BevacizumabDRUG

Bevacizumab (Avastin®) concentrate at 25mg/mL is diluted at 5 mg/kg for infusion every 14 days for 6 consecutive administrations

Bevacizumab
sodium chloride 0.9%DRUG

0.9% of sodium chloride is infused every 14 days for 6 consecutive administrations

Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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
  • 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 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.
  • Severe peripheral arterial disease with ulcerations
  • Unhealed wound
  • Anticoagulant treatment
  • Uncontrolled high blood pressure

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

CHU d'Angers

Angers, France

Location

Hôpital Ambroise Paré

Boulogne-Billancourt, France

Location

Hôpital Femme Mère Enfant

Bron, France

Location

CHU de Montpellier Hôpital St Eloi

Montpellier, France

Location

Related Publications (1)

  • 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.

    PMID: 37592715RESULT

MeSH Terms

Conditions

Telangiectasia, Hereditary Hemorrhagic

Interventions

BevacizumabSodium Chloride

Condition Hierarchy (Ancestors)

Hemostatic DisordersVascular DiseasesCardiovascular DiseasesTelangiectasisHemorrhagic DisordersHematologic DiseasesHemic and Lymphatic DiseasesVascular MalformationsCardiovascular AbnormalitiesCongenital AbnormalitiesCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsChloridesHydrochloric AcidChlorine CompoundsInorganic ChemicalsSodium Compounds

Study Officials

  • DUPUIS-GIROD, MD

    Hospices Civils de Lyon

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 21, 2017

First Posted

July 24, 2017

Study Start

September 28, 2017

Primary Completion

May 15, 2020

Study Completion

May 15, 2020

Last Updated

August 6, 2025

Record last verified: 2020-06

Data Sharing

IPD Sharing
Will not share

Locations

FR(4)