Timolol Gel for Epistaxis in Hereditary Hemorrhagic Telangiectasia

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

Sponsors

Lead Sponsor: Washington University School of Medicine

Source Washington University School of Medicine
Brief 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.

Detailed 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.

Overall Status Recruiting
Start Date October 20, 2019
Completion Date October 20, 2020
Primary Completion Date October 20, 2020
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Epistaxis Severity Scale Baseline to 8-week follow-up
Secondary Outcome
Measure Time Frame
Clinical Global Impression - Improvement (CGI-I) Score Baseline to 8-week follow-up
Mean Change in Hemoglobin Baseline to 8-week follow-up
HHT endoscopic scale (HES) Baseline to 8-week follow-up
Enrollment 30
Condition
Intervention

Intervention Type: Drug

Intervention Name: Timolol Gel

Description: 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.

Arm Group Label: Timolol Gel Arm

Intervention Type: Drug

Intervention Name: Placebo Gel

Description: Placebo gel is prepared with poloxamers and no active ingredients.

Arm Group Label: Placebo Gel Arm

Eligibility

Criteria:

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 β adrenergic blocker administration

1. Hypersensitivity to β 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 β-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

Gender: All

Minimum Age: 20 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Jay F Piccirillo, MD Principal Investigator Washington University School of Medicine
Overall Contact

Last Name: Andrew M Peterson

Phone: 314-747-0910

Email: [email protected]

Location
Facility: Status: Contact: Contact Backup: Washington University Andrew M. Peterson 314-747-0910 [email protected]
Location Countries

United States

Verification Date

December 2019

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Washington University School of Medicine

Investigator Full Name: Jay F. Piccirillo, MD

Investigator Title: Professor and Vice Chair for Research, Department of Otolaryngology - Head and Neck Surgery

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Timolol Gel Arm

Type: Experimental

Description: Participants in the timolol gel arm (active medication arm) will receive timolol nasal gel 0.1% with 0.5 mL applied to each nostril twice daily via a syringe that will amount to a 2 mg total daily dose.

Label: Placebo Gel Arm

Type: Placebo Comparator

Description: Participants in the placebo gel arm will receive the gel itself with no active medication.

Acronym ETIC-HHT
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov