Timolol Gel for Epistaxis in Hereditary Hemorrhagic Telangiectasia

Hereditary Hemorrhagic Telangiectasia Clinical Trial

— ETIC-HHT  

Official title:

Efficacy of a Timolol Gel in the Care for Epistaxis in Patients With Hereditary Hemorrhagic Telangiectasia: A Double-Blinded, Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04139018
• Other study ID #: 201908160
• Status: Completed
• Phase: Phase 2
• Start date: October 20, 2019
• Est. completion date: May 20, 2020

Study information

• Verified date: July 2021
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a double-blinded, randomized controlled trial to evaluate the efficacy of an intranasal topical timolol gel in the care for epistaxis in adults with hereditary hemorrhagic telangiectasia.

Description:

This study is a double-blinded, placebo-controlled, 8-week randomized clinical trial investigating the efficacy of timolol gel in the management of epistaxis in adults with HHT.

The Specific Aims are to determine in adults with HHT-associated epistaxis:

1. If topical timolol gel is more effective than placebo in reducing the frequency and severity of epistaxis.

2. If topical timolol gel is more effective than placebo in improving hemoglobin levels.

3. The frequency of adverse events, side effects, and safety profile of topical timolol gel delivered to the nasal mucosa.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: May 20, 2020
• Est. primary completion date: May 20, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

1. Adults ages 20 and older

2. Confirmed clinical (meeting at least 3 of the 4 Curaçao Criteria) or genetic diagnosis of HHT

3. Epistaxis Severity Score (ESS) = 4 and 2 or more nosebleeds per week with a cumulative nosebleed duration of at least 5 minutes per week

4. Stable nasal hygiene and medical regimen for preceding 1 month

5. Stable epistaxis pattern over the preceding 3 months

Exclusion Criteria:

1. Contraindications for systemic ß adrenergic blocker administration

1. Hypersensitivity to ß adrenergic blockers

2. Asthma or bronchospasm

3. Congestive heart failure with LVEF <40%

4. Hereditary pulmonary arterial hypertension

5. Baseline bradycardia (HR <55 beats per minute)

6. Sick Sinus Syndrome

7. 2nd or 3rd degree heart block, left or right bundle branch block, or bifasicular block

8. Uncontrolled diabetes mellitus (most recent HbA1c >9%) or diabetic ketoacidosis within last 6 months

9. Hypotension (systolic blood pressure < 90)

2. Known hypersensitivity to timolol

3. Severe peripheral circulatory disturbances (Raynaud phenomenon)

4. Known intermediate or poor metabolizer variant of the liver enzyme CYP2D6

5. Current use of any of the following known strong CYP2D6 inhibitors: fluoxetine (Prozac), paroxetine (Paxil), bupropion (Welbutrin), quinidine, quinine, ritonavir (Norvir), and terbinafine (Lamisil)

6. Current use of the following other drugs known to pharmacodynamically interact with timolol: diltiazem, verapamil, digoxin, digitalis, propafenone, disopyramide, clonidine, flecainide, or lidocaine

7. Patients currently treated or who plan to initiate treatment with ß-blockers

8. Use of any anti-angiogenic medication in the last month prior to recruitment, including bevacizumab, pazopanib, thalidomide, or lenalidomide

9. Illicit drug use, except marijuana

10. Known pheochromocytoma

11. Use of anticoagulants, antiplatelet, or fibrinolytic therapies within the last month prior to recruitment, except for low-dose (81 mg or less) of aspirin

12. Pregnancy or planned pregnancy in the next 6 months or currently breastfeeding

13. Inability to read or understand English

14. Inability to complete 8 weeks of therapy for any reason

Related Conditions & MeSH terms

• Epistaxis
• Hereditary Hemorrhagic Telangiectasia
• Telangiectasia, Hereditary Hemorrhagic
• Telangiectasis

Intervention

Drug:
• Timolol Gel
Timolol nasal gel 0.1% will be prepared with a poloxamer gel (combination of poloxamer 188 and 407; pH adjusted to 4.5-6.5) and 0.5 ml applied to each nostril twice daily. The total daily dose would amount to 2 mg.
• Placebo Gel
Placebo gel is prepared with poloxamers and no active ingredients.

Locations

Country	Name	City	State
United States	Washington University	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Assisted Epistaxis Severity Scale (aESS) Score From Baseline at 8 Week Follow-up	Assessment of epistaxis severity will be obtained by the validated instrument, the Epistaxis Severity Score (ESS). To complete the ESS, patients are asked to consider typical symptoms over the previous 3 months. The ESS contains 6 items - frequency, duration, and intensity of nosebleeds, whether patient has sought medication attention, whether patient is anemic, and whether patient has received a blood transfusion. The overall score ranges from 0 to 10, with severity of nosebleed based on score graded as None composite score of 0-1, Mild 1-4, Moderate 4-7, and Severe as 7-10.The minimal important difference noticeable by both patients and clinicians in the ESS scoring system is estimated as a change of 0.71. The scoring and MCID of the aESS is the same as the ESS.; The aESS references a participant's epistaxis over the past 1 month, and the change in aESS was calculated as the aESS score at 8 weeks minus the aESS score at baseline.	Baseline to 8-week follow-up
Secondary	Number of Participants With Improved Response on Clinical Global Impression - Improvement (CGI-I) Scale	CGI-I is a global rating of improvement scale, which requires subjects to rate their degree of improvement on a seven-point scale: "Compared to your condition at admission to the project [prior to medication initiation], how would you rate your overall response: 1=very much improved since the initiation of treatment; 2=much improved; 3=minimally improved; 4=no change from baseline (the initiation of treatment); 5=minimally worse; 6= much worse; 7=very much worse since the initiation of treatment."	Scores at 8-week follow-up only