Efficacy of a Timolol Nasal Spray as a Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT) - (TEMPO)

Civil Hospices of Lyon

Status and phase

Completed

Phase 2

Conditions

Telangiectasia, Hereditary Hemorrhagic

Osler Rendu Disease

Treatments

Drug: Timolol nasal spray

Drug: Placebo nasal spray

Study type

Interventional

Funder types

Other

Identifiers

NCT02484716

2015-000385-55 (EudraCT Number)

69HCL15_0063

Details and patient eligibility

About

Timolol is a nonselective β-blocker commonly used in the treatment of glaucoma. Recently it has been used topically for the treatment of superficial hemangiomas. Because of its potential mechanism of action, it is possible that timolol could also be useful for the treatment of epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT). Moreover a case was reported in 2012 showing an improvement of nosebleeds with the use of topical nasal timolol. The aim of the study is to evaluate timolol nasal spray efficacy in HHT.

The main objective of this trial is to evaluate, 3 months after the end of the treatment, the efficacy on the duration of nosebleeds of a 4 weeks timolol intranasal treatment in HHT patients with nosebleeds (>20 min/month). Secondary objectives are to evaluate the tolerance, the efficacy at 6 months after the end of the treatment, and the efficacy on anemia and on clinical parameters (nosebleeds, quality of life and blood transfusions).

This is a prospective double blind phase II study, randomized versus placebo using an allocation ratio of 1:1. A total of 58 patients will be included. The product (solution with timolol at 0.5% or placebo) is self-administered by the patient with a posology of one spray (50 µL) in each nostril twice a day for 28 consecutive days.

Enrollment

58 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age > 18 years
Patients who give voluntary, informed consent and sign a consent form.
Patients affiliated with the French universal health care system
Patients treated for HHT, that has been confirmed clinically (presence of at least 3 Curaçao criteria) and/or by molecular biology.
Patients who present epistaxis averaging over 20 minutes in the three months before inclusion, justified by completed epistaxis tally sheets.

Exclusion criteria

Pregnant women or women who could become pregnant during the study, or during lactation
Patients not affiliated with the French universal health care system
Patients who are protected adults according to the terms of the law (French public health laws).
Refusal to give consent.
Patients whose HHT diagnosis has not be confirmed clinically and/or by molecular biology.
Participation in another therapeutic trial which could interfere with the present trial (investigator jugement).
Bronchial asthma, presence or history of severe chronic obstructive pulmonary disease
Cardiac history : cardiac failure or cardiogenic shock. Atrioventricular block (second or third degrees) not controlled with pace-maker or sinus disease (included sinoatrial block) confirmed by ECG less than one year. Ongoing treatment by calcium antagonists (bépridil, diltiazem, verapamil) or antiarrhytmics (propafénone, quinidine, hydroquinidine, disopyramide) or clonidine or lidocaîne. Ongoing beta-blocker treatment.
Bradycardia (<50 pulse per minute)
Hypotension (PAS < 90 Hg mm)
Angina
Not controlled Pheochromocytoma
Severe peripheral circulatory disturbances (Raynaud disease)
Hypersensitivity to the active substance, any of the excipients or other beta-blocking agents
Ongoing treatment by floctafénine or sultopride or amiodarone
Patients who do not complete epistaxis grids for three months before treatment
Patients who present epistaxis averaging below 20 minutes in the three months before inclusion