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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03227263
Other study ID # 69HCL17_0018
Secondary ID 2017-001031-39
Status Completed
Phase Phase 3
First received
Last updated
Start date September 28, 2017
Est. completion date May 15, 2020

Study information

Verified date June 2020
Source Hospices Civils de Lyon
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The recognized manifestations of HHT are all due to abnormalities of vascular structure. Epistaxis and digestive arteriovenous malformations may be responsible for severe hemorrhages in 5% of HHT patients, requiring repeated blood transfusions and are associated with high morbidity. There is currently no standard and efficient management of this severe symptom. It is also well known that HHT-associated hemorrhages have the greatest negative impact on quality of life among HHT patients, and is responsible for anemia, blood transfusions, hospitalizations, depressive syndrome and a high psycho-social impact. Since 2006, it has been suggested by animal models and then by clinical reports that anti-VEGF therapy may be useful to treat HHT. 4 case reports have been published on efficacy of intravenous bevacizumab, a humanized monoclonal antibody in HHT on severe hemorrhages. Intravenous bevacizumab has been used in a previous clinical trial to measure efficacy and tolerance of this drug in HHT patients with severe liver involvement. Furthermore, a reduction was observed in the duration of the nosebleeds after treatment and was encouraging to treat bleeding. We completed this study by a pharmacokinetic-pharmacodynamic (PK-PD) model in order to assess the individual concentration-effect relationship of bevacizumab. However, no randomized prospective study has been performed and published to evaluate the efficacy in this indication. A total of 24 patients will be randomized versus placebo in a multicenter phase III trial. The Avastin or placebo will be infused at 5mg/kg every 14 days with a total of 6 cures with a 3 months following period.


Recruitment information / eligibility

Status Completed
Enrollment 24
Est. completion date May 15, 2020
Est. primary completion date May 15, 2020
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Age = 18 years. - Patients who have given their free informed and signed consent. - Patients affiliated to a social security scheme or similar. - Patients monitored for clinically confirmed HHT (presence of at least three Curaçao criteria) and / or with molecular biology confirmation. - Blood transfusions with the requirement for at least 4 units of blood in the 3-month period before study enrollment, related to epistaxis or digestive bleeding. Exclusion Criteria: - Women who are pregnant or nursing (lactating), women of child-bearing potential without reliable contraception during the treatment and for at least 6 months after the last dose. - Patients who are protected adults under the terms of the law (French Public Health Code). - Refusal to consent. - Patients for whom the diagnosis of HHT has not been confirmed clinically and / or by molecular biology study. - Active infection and/or fever>38°C - Participation in another clinical trial within 28 days prior to inclusion. - Hypersensitivity to the active substance or to any of the excipients. - Known hypersensitivity to products of Chinese hamster ovary cells (CHO) or other recombinant human or humanized antibodies. - Patients who have taken Avastin ® intravenously in the 6 months prior to inclusion. - Patients who have had a therapeutic endoscopy for gastrointestinal bleeding or ENT surgery for epistaxis will have to wait at least 3 months less after treatment to be included if bleeding persists. - Patients who had a surgery in the month prior inclusion or planned surgery within 6 months - Severe peripheral arterial disease with ulcerations - Unhealed wound - Thrombosis in the 6 months prior to inclusion - Anticoagulant treatment - Uncontrolled high blood pressure

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Bevacizumab
Bevacizumab (Avastin®) concentrate at 25mg/mL is diluted at 5 mg/kg for infusion every 14 days for 6 consecutive administrations
sodium chloride 0.9%
0.9% of sodium chloride is infused every 14 days for 6 consecutive administrations

Locations

Country Name City State
France CHU d'Angers Angers
France Hôpital Ambroise Paré Boulogne Billancourt
France Hôpital Femme Mère Enfant Bron
France CHU de Montpellier Hôpital St Eloi Montpellier

Sponsors (1)

Lead Sponsor Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type Measure Description Time frame Safety issue
Primary number of red blood cell transfusions 6 months
Secondary hemoglobin The relative evolution in hemoglobin level at 3 months after the beginning of the treatment is compared to the value measured at inclusion 3 months
Secondary hemoglobin The relative evolution in hemoglobin level at 6 months after the beginning of the treatment is compared to the value measured at inclusion 6 months
Secondary epistaxis frequency Comparison of an average over a 3-month period before and after the treatment. 3 months before treatment up to 6 months from the inclusion
Secondary duration of nosebleeds Comparison of an average over a 3-month period before and after the treatment. 3 months before treatment up to 6 months from the inclusion
Secondary digestive vascular malformations Comparison of digestive endoscopy before and after treatment if gastrointestinal bleeding have already externalized before treatment 6 months
Secondary quality of life (SF36). Comparison of SF36 questionnaire before and after treatment. 3 months
Secondary quality of life (SF36). Comparison of SF36 questionnaire before and after treatment. 6 months
Secondary severity epistaxis score (ESS). Comparison of ESS questionnaire before and after treatment 3 months
Secondary severity epistaxis score (ESS). Comparison of ESS questionnaire before and after treatment 6 months.
Secondary To evaluate pharmacokinetics of bevacizumab dose Description of bevacizumab serum concentrations over time, the relationship between bevacizumab concentrations and adverse events and clinical/biological endpoints Before each 6 infusions
Secondary To evaluate pharmacokinetics of bevacizumab dose Description of bevacizumab serum concentrations over time, the relationship between bevacizumab concentrations and adverse events and clinical/biological endpoints 2 hours after the first treatment infusion
Secondary adverse events To assess the safety of bevacizumab.Tolerance will be evaluated by recording adverse events and by clinical examinations during the treatment period and the follow up period. up to 6 months
See also
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Completed NCT03910244 - Pomalidomide for the Treatment of Bleeding in HHT Phase 2
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Recruiting NCT00230620 - Molecular Studies on Hereditary Haemorrhagic Telangiectasia Families
Recruiting NCT02157987 - Treatment of Hereditary Hemorrhagic Telangiectasia of the Nasal Mucosa by Intranasal Bevacizumab : Search for Effective Dose Phase 1/Phase 2
Completed NCT01408030 - North American Study of Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT) Phase 2
Completed NCT00230659 - Investigation of Coagulation Parameters in Hereditary Haemorrhagic Telangiectasia
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Active, not recruiting NCT00230633 - Studies of White Blood Cells Derived From HHT Patients
Recruiting NCT05933330 - Hereditary Hemorrhagic Telangiectasia and Neurovascular Manifestations, in the Danish HHT Database