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

Telangiectasia, Hereditary Hemorrhagic Clinical Trial

— TEMPO  

Official title:

Efficacy of a Timolol Nasal Spray as a Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT) - Randomized Trial Versus Placebo

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02484716
• Other study ID #: 69HCL15_0063
• Secondary ID: 2015-000385-55
• Status: Completed
• Phase: Phase 2
• Start date: June 2015
• Est. completion date: January 29, 2018

Study information

• Verified date: January 2018
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: January 29, 2018
• Est. primary completion date: November 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Timolol nasal spray
Timolol 0.5% is administered by the patient with a posology of one spray (50 µL) in each nostril twice a day for 4 weeks.
• Placebo nasal spray
Placebo (NaCl) is administered by the patient with a posology of one spray (50 µL) in each nostril twice a day for 4 weeks.

Locations

Country	Name	City	State
France	Hospices Civils de Lyon - Hôpital Femme Mère Enfant / Service de génétique Clinique	Bron

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy of timolol nasal spray on duration of nosebleeds for 3 months after the end of the treatment.	comparison of mean monthly epistaxis duration 3 months before the treatment and 3 months after the end of the treatment.	Day 0 (inclusion) ; up to 4 months
Secondary	Tolerance of timolol nasal spray in patients with HHT-related epistaxis	Tolerance will be evaluated by observing adverse effects and clinical examinations during the follow up period.	up to 7 months
Secondary	Efficacy on clinical criteria : epistaxis frequency .	Comparison of number of epistaxis before and after treatment.	Day 0 (inclusion) ; up to 4 months
Secondary	Efficacy on clinical criteria : biological parameters (hemoglobin and ferritin level).	Comparison of hemoglobin and ferritin level before and after treatment.	Day 0 (inclusion) ; up to 4 months
Secondary	Efficacy on clinical criteria : quality of life (SF36).	Comparison of SF36 questionnaire before and after treatment.	Day 0 (inclusion) ; up to 4 months
Secondary	Efficacy of timolol nasal spray on duration of nosebleeds for 6 months after the end of the treatment.	Comparison of mean monthly epistaxis duration 3 months before the treatment and 6 months after the end of the treatment.	Day 0 (inclusion) ; up to 7 months

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