Trial | NCT04113187  Report issue

Title

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

  • Phase

    Phase 3

  • Study Type

    Interventional

  • Status

    Completed No Results Posted

  • Study Participants

    15
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.
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 Started
Jun 23
2020
Primary Completion
May 19
2022
Study Completion
May 19
2022
Last Update
Jun 14
2022

Drug Propranolol treatment

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

Drug Placebo

per os, twice a day (morning and evening) during three months

Propranolol arm Experimental

Placebo arm Placebo Comparator

Criteria 

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
No Results Posted