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

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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

Tracking Information
First Submitted Date  ICMJE July 21, 2017
First Posted Date  ICMJE July 24, 2017
Last Update Posted Date July 10, 2018
Actual Study Start Date  ICMJE September 28, 2017
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 21, 2017)
number of red blood cell transfusions [ Time Frame: 6 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03227263 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 21, 2017)
  • 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
  • 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
  • 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.
  • 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.
  • digestive vascular malformations [ Time Frame: 6 months ]
    Comparison of digestive endoscopy before and after treatment if gastrointestinal bleeding have already externalized before treatment
  • quality of life (SF36). [ Time Frame: 3 months ]
    Comparison of SF36 questionnaire before and after treatment.
  • quality of life (SF36). [ Time Frame: 6 months ]
    Comparison of SF36 questionnaire before and after treatment.
  • severity epistaxis score (ESS). [ Time Frame: 3 months ]
    Comparison of ESS questionnaire before and after treatment
  • severity epistaxis score (ESS). [ Time Frame: 6 months. ]
    Comparison of ESS questionnaire before and after treatment
  • 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
  • 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
  • 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.
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 BABH Study: Efficacy and Safety of Bevacizumab on Severe Bleedings Associated With Hemorrhagic Hereditary Telangiectasia (HHT).
Official Title  ICMJE BABH Study: Efficacy and Safety of Bevacizumab on Severe Bleedings Associated With Hemorrhagic Hereditary Telangiectasia (HHT). A National, Multicenter Phase III Study
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Hemorrhagic Hereditary Telangiectasia (HHT)
Intervention  ICMJE
  • Drug: Bevacizumab
    Bevacizumab (Avastin®) concentrate at 25mg/mL is diluted at 5 mg/kg for infusion 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
Study Arms  ICMJE
  • Experimental: Bevacizumab
    Intravenous infusion of Bevacizumab at a dose of 5 mg/kg
    Intervention: Drug: Bevacizumab
  • Placebo Comparator: Placebo
    0.9% of sodium chloride is infused every 14 days for 6 consecutive administrations
    Intervention: Drug: sodium chloride 0.9%
Publications * Not Provided

*   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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 21, 2017)
24
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2020
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Sophie DUPUIS-GIROD, MD 4 27 85 65 25 ext +33 sophie.dupuis-girod@chu-lyon.fr
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03227263
Other Study ID Numbers  ICMJE 69HCL17_0018
2017-001031-39 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Hospices Civils de Lyon
Study Sponsor  ICMJE Hospices Civils de Lyon
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: DUPUIS-GIROD, MD Hospices Civils de Lyon
PRS Account Hospices Civils de Lyon
Verification Date July 2018

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