Propranolol for Epistaxis in Hereditary Hemorrhagic Telangiectasia Patients (EPERO)

June 13, 2022 updated by: University Hospital, Bordeaux

Study of the Efficacy of Propranolol for the Management of Epistaxis in Hereditary Hemorrhagic Telangiectasia Patients

Hereditary Hemorrhagic Telangiectasia (HHT) is a genetic disorder of angiogenesis associated with disabling epistaxis. Management of these nose bleedings requires more effective treatment. Propranolol, a beta-blocker, is a potentially useful therapeutic considering its anti-angiogenic properties. Our objective is to explore the efficacy of propranolol, three months after its introduction, on the cumulative duration of epistaxis in HHT patients.

Study Overview

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

Interventional

Enrollment (Actual)

15

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Bordeaux, France
        • CHU de Bordeaux - service de médecine interne

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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
per os, twice a day (morning and evening) during three months
Experimental: Propranolol arm
40 mg twice a day (morning and evening), per os, during three months

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)
6 months after baseline (Day 0)

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
At baseline (Day 0), 3 months and 6 months after baseline
Number of cutaneous telangiectasia on hands and face
Time Frame: At baseline (Day 0), 3 months and 6 months after baseline.
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.
At baseline (Day 0), 3 months and 6 months after baseline.
Levels of ferritin
Time Frame: At baseline (Day 0), 3 months and 6 months after baseline.
At baseline (Day 0), 3 months and 6 months after baseline.
Number of red blood cells transfusions
Time Frame: At baseline (Day 0), 3 months and 6 months after baseline.
At baseline (Day 0), 3 months and 6 months after baseline.
Short Form (SF) 36 Health Survey
Time Frame: At baseline (Day 0), 3 months and 6 months after baseline.
At baseline (Day 0), 3 months and 6 months after baseline.
Number of adverse events
Time Frame: 3 months and 6 months after baseline (Day 0).
3 months and 6 months after baseline (Day 0).
Measurement of blood pressure
Time Frame: At baseline (Day 0), 1 month, 3 months and 6 months after baseline.
At baseline (Day 0), 1 month, 3 months and 6 months after baseline.
Measurement of heart rate
Time Frame: At baseline (Day 0), 1 month, 3 months and 6 months after baseline.
At baseline (Day 0), 1 month, 3 months and 6 months after baseline.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Chair: Antoine BENARD, MD, PhD, University Hospital, Bordeaux
  • Principal Investigator: Anne CONTIS, MD, University Hospital, Bordeaux

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 23, 2020

Primary Completion (Actual)

May 19, 2022

Study Completion (Actual)

May 19, 2022

Study Registration Dates

First Submitted

September 27, 2019

First Submitted That Met QC Criteria

October 1, 2019

First Posted (Actual)

October 2, 2019

Study Record Updates

Last Update Posted (Actual)

June 14, 2022

Last Update Submitted That Met QC Criteria

June 13, 2022

Last Verified

June 1, 2022

More Information

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.

Clinical Trials on Hereditary Hemorrhagic Telangiectasia

Clinical Trials on Propranolol treatment

3
Subscribe