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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00843440
Recruitment Status : Completed
First Posted : February 13, 2009
Last Update Posted : May 30, 2013
Information provided by (Responsible Party):
Hospices Civils de Lyon

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.

Condition or disease Intervention/treatment Phase
Hemorrhagic Hereditary Telangiectasia Drug: Bevacizumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Bevacizumab for the Treatment Hemorrhagic Hereditary Telangiectasia (HHT) Associated With Severe Hepatic Vascular Malformations. Phase II Study.
Study Start Date : March 2009
Actual Primary Completion Date : March 2009
Actual Study Completion Date : March 2012

Arm Intervention/treatment
Experimental: Bevacizumab
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
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.
Other Name: AVASTIN

Primary Outcome Measures :
  1. cardiac output measured at 3 months [ Time Frame: 3 months ]

Secondary Outcome Measures :
  1. Evaluation at 6 and 12 months [ Time Frame: 12 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • • 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.
  • The presence of atrial fibrillation on the electrocardiogram at the inclusion.
  • The presence of cerebral arteriovenous malformations on the angioMRI done in the year prior to inclusion.
  • Existence of diverticulitis of the colon or sigmoid
  • Thrombosis within 6 months before inclusion
  • Infectious disease treated by antibiotics and unresolved at inclusion.
  • Patients with blood pressure that is not being controlled at the time of inclusion (systolic blood pressure> 150 mmHg and / or diastolic> 100 mmHg) with or without treatment. Patients who have high blood pressure can be included when the blood pressure numbers have been standardized by appropriate medical treatment.

    • 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.
  • Use of oral or parenteral anticoagulants or thrombolytic agents within 28 days preceding inclusion (anticoagulants given prophylactically are permitted).
  • Participation in another clinical trial within 28 days preceding inclusion.
  • Vaccination with live vaccines or against yellow fever during the treatment period.
  • Administration of phenytoin (Di-hydan ® DILANTIN ®) during the treatment period.

    • Allergy

  • Hypersensitivity to the active substance or any of its excipients.
  • Hypersensitivity to products made from Chinese hamster ovary (CHO) cells or to any other human or humanized recombinant antibodies.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00843440

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Hospices Civils de Lyon
Lyon, France
Sponsors and Collaborators
Hospices Civils de Lyon
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Principal Investigator: Sophie DUPUIS-GIROD, MD Hospices Civils de Lyon
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Hospices Civils de Lyon Identifier: NCT00843440    
Other Study ID Numbers: 2008.510/11
First Posted: February 13, 2009    Key Record Dates
Last Update Posted: May 30, 2013
Last Verified: October 2009
Keywords provided by Hospices Civils de Lyon:
Antiangiogenic therapies
Hemorrhagic Hereditary Telangiectasia (HHT) with severe liver involvement
Additional relevant MeSH terms:
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Vascular Malformations
Congenital Abnormalities
Vascular Diseases
Cardiovascular Diseases
Cardiovascular Abnormalities
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors