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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.
 
ClinicalTrials.gov Identifier: NCT00843440
Recruitment Status : Completed
First Posted : February 13, 2009
Last Update Posted : May 30, 2013
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon

Tracking Information
First Submitted Date  ICMJE February 12, 2009
First Posted Date  ICMJE February 13, 2009
Last Update Posted Date May 30, 2013
Study Start Date  ICMJE March 2009
Actual Primary Completion Date March 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 12, 2009)
cardiac output measured at 3 months [ Time Frame: 3 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 12, 2009)
Evaluation at 6 and 12 months [ Time Frame: 12 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Bevacizumab for the Treatment Hemorrhagic Hereditary Telangiectasia (HHT) Associated With Severe Hepatic Vascular Malformations. Phase II Study
Official Title  ICMJE Efficacy and Safety of Bevacizumab for the Treatment Hemorrhagic Hereditary Telangiectasia (HHT) Associated With Severe Hepatic Vascular Malformations. Phase II Study.
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hemorrhagic Hereditary Telangiectasia
Intervention  ICMJE 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
Study Arms  ICMJE 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.
Intervention: Drug: Bevacizumab
Publications * 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, Rivière 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 12, 2009)
25
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 2012
Actual Primary Completion Date March 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00843440
Other Study ID Numbers  ICMJE 2008.510/11
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hospices Civils de Lyon
Study Sponsor  ICMJE Hospices Civils de Lyon
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Sophie DUPUIS-GIROD, MD Hospices Civils de Lyon
PRS Account Hospices Civils de Lyon
Verification Date October 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP