- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04113187
Propranolol for Epistaxis in Hereditary Hemorrhagic Telangiectasia Patients (EPERO)
Study of the Efficacy of Propranolol for the Management of Epistaxis in Hereditary Hemorrhagic Telangiectasia Patients
Study Overview
Status
Intervention / Treatment
Detailed Description
Hereditary Hemorrhagic Telangiectasia (HHT) is a rare systemic autosomal dominantly inherited disorder of angiogenesis. Its major feature is the occurrence in 90% of patients of spontaneous and recurrent epistaxis responsible for iron deficiency and chronic anemia. Various conservative and interventional treatments have been described for these conditions, but no optimal therapy exists. Inhibiting angiogenesis process is an interesting therapeutic option. Propranolol, a non-cardio-selective beta-blocker, could represent a new candidate for the therapy of HHT telangiectasia as it suppresses angiogenesis in vitro. This anti-angiogenic property is well-known in pediatric dermatology, since C. Léauté-Labrèze and al. have demonstrated a great improvement of infantile hemangioma undergoing propranolol treatment. At the University Hospital Center of Bordeaux, the investigators assessed in a preliminary study the efficacy of propranolol for HHT epistaxis. Nine of ten patients receiving propranolol for cardiologic or neurologic indications, retrospectively analyzed, significantly improved their Epistaxis Severity Score. Ten patients were then prospectively included and after 3 months of propranolol treatment, the median duration of epistaxis per month significantly decreased (p=0,007) as well as the number of epistaxis episodes per month (p=0,015).
To confirm these results, the investigators would like to study the efficacy of propranolol given per os at the dose of 40 mg twice a day for a three-months period, in comparison to a placebo. Throughout the study, patients will complete specific grids recording the number of epistaxis episodes per month and the cumulative duration of nose bleedings. A follow-up of 6 months will be done (4 visits after inclusion), recording clinical and biological data and monitoring the tolerance of treatment.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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-
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Bordeaux, France
- CHU de Bordeaux - service de médecine interne
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age ≥ 18 years
- Confirmed diagnosis of HHT : 3 or more Curaçao criteria (spontaneous and recurrent epistaxis; multiple telangiectasia at characteristic sites; visceral lesions such as gastrointestinal telangiectasia or arteriovenous malformations; family history: a first degree relative with HHT according to these criteria ) or mutations of genes encoding for ALK1, ENG or SMAD4
- Patient suffering from recurrent epistaxis (more than a mean of 10 episodes/month) and/or with a cumulative mean duration per month more than 20 minutes, according to specific grids completed at least three months before inclusion.
- Patient insured under the French social security system
- Free and informed consent signed by investigator and patient
Exclusion Criteria:
- Pregnancy or breast-feeding
- Incomplete epistaxis grids in the month prior inclusion
- Current beta-blocker treatment
- Hypersensitivity to the active substance or excipient
- Patients with type I or type II diabetes, treated with insulin, sulphonylureas or meglitinides
- Patients with heart failure
- Patients with liver failure
- Patients with hepatic arteriovenous malformations responsible for high-output cardiac failure or severe hepatic dysfunction
- Patients with severe psoriasis (PASI>10)
- Contra-indication to beta-blocker treatment : asthma, chronic obstructive bronchopneumopathy, atrioventricular block of second or third degrees without pacemaker, Prinzmetal's angina, bradycardia < 50bpm, Raynaud's phenomenon, oblitering arteriopathy of the lower limbs, low blood pressure, non-treated pheochromocytoma
- Participation in another clinical therapeutic trial less than 3 months before inclusion
- Protected adult according to french law
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo arm
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per os, twice a day (morning and evening) during three months
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Experimental: Propranolol arm
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40 mg twice a day (morning and evening), per os, during three months
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Cumulative duration of epistaxis (in minutes)
Time Frame: 6 months after baseline (Day 0)
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6 months after baseline (Day 0)
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Frequency of epistaxis (number of episodes) per month
Time Frame: At baseline (Day 0), 3 months and 6 months after baseline
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At baseline (Day 0), 3 months and 6 months after baseline
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Number of cutaneous telangiectasia on hands and face
Time Frame: At baseline (Day 0), 3 months and 6 months after baseline.
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At baseline (Day 0), 3 months and 6 months after baseline.
|
Levels of hemoglobin
Time Frame: At baseline (Day 0), 3 months and 6 months after baseline.
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At baseline (Day 0), 3 months and 6 months after baseline.
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Levels of ferritin
Time Frame: At baseline (Day 0), 3 months and 6 months after baseline.
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At baseline (Day 0), 3 months and 6 months after baseline.
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Number of red blood cells transfusions
Time Frame: At baseline (Day 0), 3 months and 6 months after baseline.
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At baseline (Day 0), 3 months and 6 months after baseline.
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Short Form (SF) 36 Health Survey
Time Frame: At baseline (Day 0), 3 months and 6 months after baseline.
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At baseline (Day 0), 3 months and 6 months after baseline.
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Number of adverse events
Time Frame: 3 months and 6 months after baseline (Day 0).
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3 months and 6 months after baseline (Day 0).
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Measurement of blood pressure
Time Frame: At baseline (Day 0), 1 month, 3 months and 6 months after baseline.
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At baseline (Day 0), 1 month, 3 months and 6 months after baseline.
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Measurement of heart rate
Time Frame: At baseline (Day 0), 1 month, 3 months and 6 months after baseline.
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At baseline (Day 0), 1 month, 3 months and 6 months after baseline.
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Antoine BENARD, MD, PhD, University Hospital, Bordeaux
- Principal Investigator: Anne CONTIS, MD, University Hospital, Bordeaux
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Cardiovascular Diseases
- Vascular Diseases
- Respiratory Tract Diseases
- Congenital Abnormalities
- Hematologic Diseases
- Hemorrhage
- Hemorrhagic Disorders
- Otorhinolaryngologic Diseases
- Hemostatic Disorders
- Signs and Symptoms, Respiratory
- Nose Diseases
- Cardiovascular Abnormalities
- Vascular Malformations
- Epistaxis
- Telangiectasis
- Telangiectasia, Hereditary Hemorrhagic
- Physiological Effects of Drugs
- Adrenergic beta-Antagonists
- Adrenergic Antagonists
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Anti-Arrhythmia Agents
- Antihypertensive Agents
- Vasodilator Agents
- Propranolol
Other Study ID Numbers
- CHUBX 2015/32
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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