Timolol Gel for Epistaxis in Hereditary Hemorrhagic Telangiectasia

NCT04139018 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 201908160
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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.

Conditions

Hereditary Hemorrhagic Telangiectasia

Keywords

Epistaxis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Number of Participants With Improved Response on Clinical Global Impression - Improvement (CGI-I) Scale

  Scores at 8-week follow-up only

Study Arms (2)

Timolol Gel Arm

EXPERIMENTAL

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.

Drug: Timolol Gel

Placebo Gel Arm

PLACEBO COMPARATOR

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

Drug: Placebo Gel

Interventions

Timolol Gel 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.

Timolol Gel Arm

Placebo Gel DRUG

Placebo gel is prepared with poloxamers and no active ingredients.

Placebo Gel Arm

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• nd 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)
• Known hypersensitivity to timolol
• Severe peripheral circulatory disturbances (Raynaud phenomenon)
• Known intermediate or poor metabolizer variant of the liver enzyme CYP2D6
• Current use of any of the following known strong CYP2D6 inhibitors: fluoxetine (Prozac), paroxetine (Paxil), bupropion (Welbutrin), quinidine, quinine, ritonavir (Norvir), and terbinafine (Lamisil)
• Current use of the following other drugs known to pharmacodynamically interact with timolol: diltiazem, verapamil, digoxin, digitalis, propafenone, disopyramide, clonidine, flecainide, or lidocaine

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• 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.

  PMID: 32940653 DERIVED

MeSH Terms

Conditions

Telangiectasia, Hereditary Hemorrhagic; Epistaxis

Condition Hierarchy (Ancestors)

Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Telangiectasis; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Vascular Malformations; Cardiovascular Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Respiratory; Signs and Symptoms

Results Point of Contact

• Title: Jay Piccirillo, M.D., Vice Chair for Research
• Organization: Washington University School of Medicine Department of Otolaryngology - Head and Neck Surgery

piccirij@wustl.edu

314-362-8641

Study Officials

• Jay F Piccirillo, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Vice Chair for Research, Department of Otolaryngology - Head and Neck Surgery

Study Record Dates

• First Submitted: October 23, 2019
• First Posted: October 25, 2019
• Study Start: October 20, 2019
• Primary Completion: May 20, 2020
• Study Completion: May 20, 2020
• Last Updated: August 24, 2021
• Results First Posted: August 24, 2021

Record last verified: 2021-07

Locations

US (1)