Efficacy and Safety of Bevacizumab for the Treatment Hemorrhagic Hereditary Telangiectasia (HHT) Associated With Severe Hepatic Vascular Malformations. Phase II Study.
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Hospices Civils de Lyon
- Enrollment
- 25
- Locations
- 1
- Primary Endpoint
- cardiac output measured at 3 months
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- 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
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
Arms & Interventions
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: Bevacizumab (Drug)
Outcomes
Primary Outcomes
cardiac output measured at 3 months
Time Frame: 3 months
Secondary Outcomes
- Evaluation at 6 and 12 months(12 months)