Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

BABH Study: Efficacy and Safety of Bevacizumab on Severe Bleedings Associated With Hemorrhagic Hereditary Telangiectasia (HHT). (BABH)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03227263
Recruitment Status : Recruiting
First Posted : July 24, 2017
Last Update Posted : July 10, 2018
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon

Brief 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.


Condition or disease Intervention/treatment Phase
Hemorrhagic Hereditary Telangiectasia (HHT) Drug: Bevacizumab Drug: sodium chloride 0.9% Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: BABH Study: Efficacy and Safety of Bevacizumab on Severe Bleedings Associated With Hemorrhagic Hereditary Telangiectasia (HHT). A National, Multicenter Phase III Study
Actual Study Start Date : September 28, 2017
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : March 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bleeding

Arm Intervention/treatment
Experimental: Bevacizumab
Intravenous infusion of Bevacizumab at a dose of 5 mg/kg
Drug: Bevacizumab
Bevacizumab (Avastin®) concentrate at 25mg/mL is diluted at 5 mg/kg for infusion every 14 days for 6 consecutive administrations

Placebo Comparator: Placebo
0.9% of sodium chloride is infused every 14 days for 6 consecutive administrations
Drug: sodium chloride 0.9%
0.9% of sodium chloride is infused every 14 days for 6 consecutive administrations




Primary Outcome Measures :
  1. number of red blood cell transfusions [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. hemoglobin [ Time Frame: 3 months ]
    The relative evolution in hemoglobin level at 3 months after the beginning of the treatment is compared to the value measured at inclusion

  2. hemoglobin [ Time Frame: 6 months ]
    The relative evolution in hemoglobin level at 6 months after the beginning of the treatment is compared to the value measured at inclusion

  3. epistaxis frequency [ Time Frame: 3 months before treatment up to 6 months from the inclusion ]
    Comparison of an average over a 3-month period before and after the treatment.

  4. duration of nosebleeds [ Time Frame: 3 months before treatment up to 6 months from the inclusion ]
    Comparison of an average over a 3-month period before and after the treatment.

  5. digestive vascular malformations [ Time Frame: 6 months ]
    Comparison of digestive endoscopy before and after treatment if gastrointestinal bleeding have already externalized before treatment

  6. quality of life (SF36). [ Time Frame: 3 months ]
    Comparison of SF36 questionnaire before and after treatment.

  7. quality of life (SF36). [ Time Frame: 6 months ]
    Comparison of SF36 questionnaire before and after treatment.

  8. severity epistaxis score (ESS). [ Time Frame: 3 months ]
    Comparison of ESS questionnaire before and after treatment

  9. severity epistaxis score (ESS). [ Time Frame: 6 months. ]
    Comparison of ESS questionnaire before and after treatment

  10. To evaluate pharmacokinetics of bevacizumab dose [ Time Frame: Before each 6 infusions ]
    Description of bevacizumab serum concentrations over time, the relationship between bevacizumab concentrations and adverse events and clinical/biological endpoints

  11. To evaluate pharmacokinetics of bevacizumab dose [ Time Frame: 2 hours after the first treatment infusion ]
    Description of bevacizumab serum concentrations over time, the relationship between bevacizumab concentrations and adverse events and clinical/biological endpoints

  12. adverse events [ Time Frame: up to 6 months ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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 ClinicalTrials.gov identifier (NCT number): NCT03227263


Contacts
Layout table for location contacts
Contact: Sophie DUPUIS-GIROD, MD 4 27 85 65 25 ext +33 sophie.dupuis-girod@chu-lyon.fr

Locations
Layout table for location information
France
Hôpital Femme Mère Enfant Recruiting
Bron, France
Contact: Sophie DUPUIS-GIROD, MD    4 27 85 65 25 ext +33    sophie.dupuis-girod@chu-lyon.fr   
Principal Investigator: Sophie DUPUIS-GIROD, MD         
Sponsors and Collaborators
Hospices Civils de Lyon
Investigators
Layout table for investigator information
Principal Investigator: DUPUIS-GIROD, MD Hospices Civils de Lyon

Layout table for additonal information
Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT03227263     History of Changes
Other Study ID Numbers: 69HCL17_0018
2017-001031-39 ( EudraCT Number )
First Posted: July 24, 2017    Key Record Dates
Last Update Posted: July 10, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hospices Civils de Lyon:
Hemorrhagic Hereditary Telangiectasia (HHT)
VEGF therapy
Bevacizumab
Additional relevant MeSH terms:
Layout table for MeSH terms
Telangiectasis
Vascular Diseases
Cardiovascular Diseases
Bevacizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors