Efficacy of a Timolol Gel in the Care for Epistaxis in Patients With Hereditary Hemorrhagic Telangiectasia: A Double-Blinded, Randomized Controlled Trial
Overview
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 27
- Locations
- 1
- Primary Endpoint
- Change in Assisted Epistaxis Severity Scale (aESS) Score From Baseline at 8 Week Follow-up
Overview
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:
- If topical timolol gel is more effective than placebo in reducing the frequency and severity of epistaxis.
- If topical timolol gel is more effective than placebo in improving hemoglobin levels.
- The frequency of adverse events, side effects, and safety profile of topical timolol gel delivered to the nasal mucosa.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 20 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Adults ages 20 and older
- •Confirmed clinical (meeting at least 3 of the 4 Curaçao Criteria) or genetic diagnosis of HHT
- •Epistaxis Severity Score (ESS) ≥ 4 and 2 or more nosebleeds per week with a cumulative nosebleed duration of at least 5 minutes per week
- •Stable nasal hygiene and medical regimen for preceding 1 month
- •Stable epistaxis pattern over the preceding 3 months
Exclusion Criteria
- •Contraindications for systemic β adrenergic blocker administration
- •Hypersensitivity to β adrenergic blockers
- •Asthma or bronchospasm
- •Congestive heart failure with LVEF \<40%
- •Hereditary pulmonary arterial hypertension
- •Baseline bradycardia (HR \<55 beats per minute)
- •Sick Sinus Syndrome
- •2nd or 3rd degree heart block, left or right bundle branch block, or bifasicular block
- •Uncontrolled diabetes mellitus (most recent HbA1c \>9%) or diabetic ketoacidosis within last 6 months
- •Hypotension (systolic blood pressure \< 90)
Arms & Interventions
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.
Intervention: Timolol Gel (Drug)
Placebo Gel Arm
Participants in the placebo gel arm will receive the gel itself with no active medication.
Intervention: Placebo Gel (Drug)
Outcomes
Primary Outcomes
Change in Assisted Epistaxis Severity Scale (aESS) Score From Baseline at 8 Week Follow-up
Time Frame: Baseline to 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.
Secondary Outcomes
- Number of Participants With Improved Response on Clinical Global Impression - Improvement (CGI-I) Scale(Scores at 8-week follow-up only)
Investigators
Jay F. Piccirillo, MD
Professor and Vice Chair for Research, Department of Otolaryngology - Head and Neck Surgery
Washington University School of Medicine