Timolol Gel for Epistaxis in Hereditary Hemorrhagic Telangiectasia (ETIC-HHT)

The Washington University

Status and phase: Completed; Phase 2

Conditions: Hereditary Hemorrhagic Telangiectasia

Treatments: Drug: Placebo Gel; Drug: Timolol Gel

Study type: Interventional

Funder types: Other

Identifiers

NCT04139018

201908160

Details and patient eligibility

About

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.

Full 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.

Enrollment: 27 patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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27 participants in 2 patient groups, including a placebo group

Timolol Gel Arm

Experimental group

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.

Treatment:

Drug: Timolol Gel

Placebo Gel Arm

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo Gel