Propranolol for Epistaxis in Hereditary Hemorrhagic Telangiectasia Patients

Hereditary Hemorrhagic Telangiectasia Clinical Trial

— EPERO  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04113187
• Other study ID #: CHUBX 2015/32
• Status: Completed
• Phase: Phase 3
• Start date: June 23, 2020
• Est. completion date: May 19, 2022

Study information

• Verified date: June 2022
• Source: University Hospital, Bordeaux
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: May 19, 2022
• Est. primary completion date: May 19, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Epistaxis
• Hereditary Hemorrhagic Telangiectasia
• Osler Weber Rendu Disease
• Telangiectasia, Hereditary Hemorrhagic
• Telangiectasis

Intervention

Drug:
• Propranolol treatment
40 mg twice a day (morning and evening), per os, during three months
• Placebo
per os, twice a day (morning and evening) during three months

Locations

Country	Name	City	State
France	CHU de Bordeaux - service de médecine interne	Bordeaux

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Bordeaux	AMRO-HHT-France - Association Maladie de Rendu-Osler

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cumulative duration of epistaxis (in minutes)		6 months after baseline (Day 0)
Secondary	Frequency of epistaxis (number of episodes) per month		At baseline (Day 0), 3 months and 6 months after baseline
Secondary	Number of cutaneous telangiectasia on hands and face		At baseline (Day 0), 3 months and 6 months after baseline.
Secondary	Levels of hemoglobin		At baseline (Day 0), 3 months and 6 months after baseline.
Secondary	Levels of ferritin		At baseline (Day 0), 3 months and 6 months after baseline.
Secondary	Number of red blood cells transfusions		At baseline (Day 0), 3 months and 6 months after baseline.
Secondary	Short Form (SF) 36 Health Survey		At baseline (Day 0), 3 months and 6 months after baseline.
Secondary	Number of adverse events		3 months and 6 months after baseline (Day 0).
Secondary	Measurement of blood pressure		At baseline (Day 0), 1 month, 3 months and 6 months after baseline.
Secondary	Measurement of heart rate		At baseline (Day 0), 1 month, 3 months and 6 months after baseline.