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

Primary Purpose

Telangiectasia, Hereditary Hemorrhagic, Osler Rendu Disease

Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Timolol nasal spray
Placebo nasal spray
Sponsored by
Hospices Civils de Lyon
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Telangiectasia, Hereditary Hemorrhagic focused on measuring Hereditary Hemorrhagic Telangiectasia (HHT), Antiangiogenic therapy, Timolol

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Hospices Civils de Lyon - Hôpital Femme Mère Enfant / Service de génétique Clinique

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Timolol

Placebo

Arm Description

Timolol 0.5% eye-drops solution packaged in a nasal spray device.

NaCl solution packaged in a nasal spray device.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Efficacy on clinical criteria : epistaxis frequency .
Comparison of number of epistaxis before and after treatment.
Efficacy on clinical criteria : biological parameters (hemoglobin and ferritin level).
Comparison of hemoglobin and ferritin level before and after treatment.
Efficacy on clinical criteria : quality of life (SF36).
Comparison of SF36 questionnaire before and after treatment.
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.

Full Information

First Posted
June 17, 2015
Last Updated
October 14, 2021
Sponsor
Hospices Civils de Lyon
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1. Study Identification

Unique Protocol Identification Number
NCT02484716
Brief Title
Efficacy of a Timolol Nasal Spray as a Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT) - (TEMPO)
Acronym
TEMPO
Official Title
Efficacy of a Timolol Nasal Spray as a Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT) - Randomized Trial Versus Placebo
Study Type
Interventional

2. Study Status

Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
June 2015 (Actual)
Primary Completion Date
November 2017 (Actual)
Study Completion Date
January 29, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospices Civils de Lyon

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Telangiectasia, Hereditary Hemorrhagic, Osler Rendu Disease
Keywords
Hereditary Hemorrhagic Telangiectasia (HHT), Antiangiogenic therapy, Timolol

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
58 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Timolol
Arm Type
Experimental
Arm Description
Timolol 0.5% eye-drops solution packaged in a nasal spray device.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
NaCl solution packaged in a nasal spray device.
Intervention Type
Drug
Intervention Name(s)
Timolol nasal spray
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo nasal spray
Intervention Description
Placebo (NaCl) is administered by the patient with a posology of one spray (50 µL) in each nostril twice a day for 4 weeks.
Primary Outcome Measure Information:
Title
Efficacy of timolol nasal spray on duration of nosebleeds for 3 months after the end of the treatment.
Description
comparison of mean monthly epistaxis duration 3 months before the treatment and 3 months after the end of the treatment.
Time Frame
Day 0 (inclusion) ; up to 4 months
Secondary Outcome Measure Information:
Title
Tolerance of timolol nasal spray in patients with HHT-related epistaxis
Description
Tolerance will be evaluated by observing adverse effects and clinical examinations during the follow up period.
Time Frame
up to 7 months
Title
Efficacy on clinical criteria : epistaxis frequency .
Description
Comparison of number of epistaxis before and after treatment.
Time Frame
Day 0 (inclusion) ; up to 4 months
Title
Efficacy on clinical criteria : biological parameters (hemoglobin and ferritin level).
Description
Comparison of hemoglobin and ferritin level before and after treatment.
Time Frame
Day 0 (inclusion) ; up to 4 months
Title
Efficacy on clinical criteria : quality of life (SF36).
Description
Comparison of SF36 questionnaire before and after treatment.
Time Frame
Day 0 (inclusion) ; up to 4 months
Title
Efficacy of timolol nasal spray on duration of nosebleeds for 6 months after the end of the treatment.
Description
Comparison of mean monthly epistaxis duration 3 months before the treatment and 6 months after the end of the treatment.
Time Frame
Day 0 (inclusion) ; up to 7 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Hospices Civils de Lyon - Hôpital Femme Mère Enfant / Service de génétique Clinique
City
Bron
ZIP/Postal Code
69500
Country
France

12. IPD Sharing Statement

Links:
URL
http://www.rendu-osler.fr
Description
Related Info

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

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