Efficacy and Safety of Bevacizumab for the Treatment Hemorrhagic Hereditary Telangiectasia (HHT) Associated With Severe Hepatic Vascular Malformations. Phase II Study

NCT00843440 | Completed Phase 2 DMC

• 1 other identifier: 2008.510/11
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The efficacy of anti-VEGF treatments such as Bevacizumab in cases of HHT can be considered because of the molecular mechanisms implied in angiogenesis and HHT, as well as the mechanisms of action of this type of treatment. Two articles that have recently reported spectacular improvement thanks to Bevacizumab in patients with HHT complicated with severe liver involvement and cardiac effects support us in this sense. Up to now, the only treatment recommended in the severe hepatic forms of HHT is a liver transplant, the disadvantages of which are both multiple and well known: long waiting lists, surgical morbidity and mortality, immunosuppressive treatment for life. Furthermore, treatment with Bevacizumab is not a contraindication, should the drug be ineffective, for a subsequent liver transplant if necessary.

Conditions

Hemorrhagic Hereditary Telangiectasia

Keywords

Antiangiogenic therapies; Bevacuzimab; Hemorrhagic Hereditary Telangiectasia (HHT) with severe liver involvement

Outcome Measures

Primary Outcomes (1)

• cardiac output measured at 3 months

  3 months

Secondary Outcomes (1)

• Evaluation at 6 and 12 months

  12 months

Study Arms (1)

Bevacizumab

EXPERIMENTAL

Study using a Gehan design, 7 patients will be included in the first phase and 18 additional patients will enter the second phase.

Drug: Bevacizumab

Interventions

Bevacizumab DRUG

5 mg / kg every 14 days with a total of 6 injections.A two-phase Gehan method will be used with a first phase designed to eliminate a non effective treatment quickly and a second phase allowing assessment of efficacy.

Also known as: AVASTIN

Bevacizumab

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• General criteria:
• Age ≥ 18 years and \< 70 years
• Subjects must have given their free and enlightened consent and have signed the consent form.
• HHT related criteria
• Patients monitored for clinically confirmed HHT disease.
• Patients with severe liver involvement in relationship with the HHT disease
• Patients with a high cardiac output on ultrasound.
• Associated disease related criteria
• Blood: neutrophil ≥ 1.0x109 / L and platelets ≥ 100x109 / L.
• INR (International Normalized Ratio) ≤ 1.5 (except for patients on anticoagulants) and TCA ≤ 1.5 x upper limit of the standard laboratory
• Renal function: creatinine ≤ 1.25 x upper limit of the standard laboratory. Patients who proteinuria to strip ≥ 2 + will have control of the Proteinuria of 24 hours to be ≤ 1g / 24 hours

You may not qualify if:

• General criteria
• Women who are pregnant or liable to become pregnant in the course of the trial.
• Patients who have reached their majority but who are protected by the terms of the law (French public health code).
• Refusal to give enlightened consent.
• Patients who are not affiliated to a health insurance regime
• Criteria for the medical history
• Patients in whom the diagnosis of HHT disease has not been confirmed.
• Existence of diverticulitis of the colon or sigmoid
• Surgical criteria
• Major surgery (including open biopsy) or severe trauma within 28 days preceding the start of treatment.
• Medical treatments
• Current or recent use of non steroidal anti-inflammatory drugs or antiplatelet therapy 10 days before the first administration of Bevacizumab.
• Vaccination with live vaccines or against yellow fever during the treatment period.
• Administration of phenytoin (Di-hydan ® DILANTIN ®) during the treatment period.
• Allergy

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Hospices Civils de Lyon

Lyon, France

Location

Related Publications (1)

• Dupuis-Girod S, Ginon I, Saurin JC, Marion D, Guillot E, Decullier E, Roux A, Carette MF, Gilbert-Dussardier B, Hatron PY, Lacombe P, Lorcerie B, Riviere S, Corre R, Giraud S, Bailly S, Paintaud G, Ternant D, Valette PJ, Plauchu H, Faure F. Bevacizumab in patients with hereditary hemorrhagic telangiectasia and severe hepatic vascular malformations and high cardiac output. JAMA. 2012 Mar 7;307(9):948-55. doi: 10.1001/jama.2012.250.

  PMID: 22396517 RESULT

Related Links

• Related Info

MeSH Terms

Conditions

Telangiectasia, Hereditary Hemorrhagic

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Telangiectasis; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Vascular Malformations; Cardiovascular Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Sophie DUPUIS-GIROD, MD

  Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2009
• First Posted: February 13, 2009
• Study Start: March 1, 2009
• Primary Completion: March 1, 2009
• Study Completion: March 1, 2012
• Last Updated: December 19, 2025

Record last verified: 2025-12

Locations

FR (1)