Timolol Gel for Epistaxis in Hereditary Hemorrhagic Telangiectasia

NCT ID: NCT04139018

Last Updated: 2021-08-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-20
• Study Completion Date: 2020-05-20

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.

Conditions

Hereditary Hemorrhagic Telangiectasia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Timolol Gel Arm

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.

Group Type: EXPERIMENTAL

Timolol Gel

Intervention Type: DRUG

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 Arm

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

Group Type: PLACEBO_COMPARATOR

Placebo Gel

Intervention Type: DRUG

Placebo gel is prepared with poloxamers and no active ingredients.

Interventions

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.

Intervention Type: DRUG

Placebo Gel

Placebo gel is prepared with poloxamers and no active ingredients.

Intervention Type: DRUG

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

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Jay F. Piccirillo, MD

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

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jay F Piccirillo, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University

St Louis, Missouri, United States

Countries

United States

References

Peterson AM, Lee JJ, Kallogjeri D, Schneider JS, Chakinala MM, Piccirillo JF. Efficacy of Timolol in a Novel Intranasal Thermosensitive Gel for Hereditary Hemorrhagic Telangiectasia-Associated Epistaxis: A Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2020 Nov 1;146(11):1006-1014. doi: 10.1001/jamaoto.2020.3025.

Reference Type: DERIVED

PMID: 32940653 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

201908160

Identifier Type: -

Identifier Source: org_study_id