Hemorrhagic Hereditary TelangiectasiaPhase 2METAFORENCT00843440
Efficacy and Safety of Bevacizumab for the Treatment Hemorrhagic Hereditary Telangiectasia (HHT) Associated With Severe Hepatic Vascular Malformations. Phase II Study
A Phase 2 study testing Bevacizumab in people with Hemorrhagic Hereditary Telangiectasia, run by Hospices Civils de Lyon at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hemorrhagic Hereditary Telangiectasia
- What is being tested?
- Bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteFrance
- Study dates
- Mar 2009to Mar 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- • 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
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Efficacy and Safety of Bevacizumab for the Treatment Hemorrhagic Hereditary Telangiectasia (HHT) Associated With Severe Hepatic Vascular Malformations. Phase II Study.
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
- Being tested
- Bevacizumab
- Keywords
- Antiangiogenic therapies, Bevacuzimab, Hemorrhagic Hereditary Telangiectasia (HHT) with severe liver involvement
- Medical subject headings
- Telangiectasia, Hereditary Hemorrhagic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Also called AVASTIN
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
cardiac output measured at 3 months
Measured: 3 months
Secondary outcomes (1)
Evaluation at 6 and 12 months
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2009 (estimated)
- Study startMar 2009
- Primary completionMar 2009
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hemorrhagic Hereditary TelangiectasiaStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sophie DUPUIS-GIROD, MD, Principal investigator, Hospices Civils de Lyon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00843440
- Sponsor's protocol ID
- 2008.510/11
- Acronym
- METAFORE
- Status last verified
- Dec 2025
- First submitted
- 12 Feb 2009
- Last updated
- 19 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
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, 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.
PubMed 22396517
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Bevacizumab for the Treatment Hemorrhagic Hereditary Telangiectasia (HHT) Associated With Severe Hepatic Vascular Malformations. Phase II Study.
- ClinicalTrials.gov ID
- NCT00843440
- Acronym / sponsor ID
- METAFORE / 2008.510/11
- Conditions
- Hemorrhagic Hereditary Telangiectasia
- Keywords
- Antiangiogenic therapies, Bevacuzimab, Hemorrhagic Hereditary Telangiectasia (HHT) with severe liver involvement
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- Mar 2009
- Primary completion
- Mar 2009 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 13 Feb 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab | Experimental | Drug: BevacizumabStudy using a Gehan design, 7 patients will be included in the first phase and 18 additional patients will enter the second phase. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- General criteria:
- HHT related criteria
- Associated disease related criteria
Key exclusion criteria (24 listed)
- • 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BevacizumabAlso: AVASTIN5 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. | Drug | Bevacizumab |
Primary outcome
cardiac output measured at 3 months
Time frame: 3 months
1 secondary outcome
Evaluation at 6 and 12 months
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2025.
- Results publication: PubMed 22396517Dupuis-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.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sophie DUPUIS-GIROD, MD principal investigator
Hospices Civils de Lyon
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bevacizumab in people with Hemorrhagic Hereditary Telangiectasia, run by Hospices Civils de Lyon at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
cardiac output measured at 3 months (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00843440, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2025.