Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04139018
Recruitment Status : Completed
First Posted : October 25, 2019
Results First Posted : August 24, 2021
Last Update Posted : August 24, 2021
Sponsor:
Information provided by (Responsible Party):
Jay F. Piccirillo, MD, 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.

Condition or disease Intervention/treatment Phase
Hereditary Hemorrhagic Telangiectasia Drug: Timolol Gel Drug: Placebo Gel Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy of a Timolol Gel in the Care for Epistaxis in Patients With Hereditary Hemorrhagic Telangiectasia: A Double-Blinded, Randomized Controlled Trial
Actual Study Start Date : October 20, 2019
Actual Primary Completion Date : May 20, 2020
Actual Study Completion Date : May 20, 2020


Arm Intervention/treatment
Experimental: 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.
Drug: 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.

Placebo Comparator: Placebo Gel Arm
Participants in the placebo gel arm will receive the gel itself with no active medication.
Drug: Placebo Gel
Placebo gel is prepared with poloxamers and no active ingredients.




Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. Number of Participants With Improved Response on Clinical Global Impression - Improvement (CGI-I) Scale [ Time Frame: Scores at 8-week follow-up only ]
    CGI-I is a global rating of improvement scale, which requires subjects to rate their degree of improvement on a seven-point scale: "Compared to your condition at admission to the project [prior to medication initiation], how would you rate your overall response: 1=very much improved since the initiation of treatment; 2=much improved; 3=minimally improved; 4=no change from baseline (the initiation of treatment); 5=minimally worse; 6= much worse; 7=very much worse since the initiation of treatment."



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04139018


Locations
Layout table for location information
United States, Missouri
Washington University
Saint Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Layout table for investigator information
Principal Investigator: Jay F Piccirillo, MD Washington University School of Medicine
  Study Documents (Full-Text)

Documents provided by Jay F. Piccirillo, MD, Washington University School of Medicine:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Jay F. Piccirillo, MD, Professor and Vice Chair for Research, Department of Otolaryngology - Head and Neck Surgery, Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT04139018    
Other Study ID Numbers: 201908160
First Posted: October 25, 2019    Key Record Dates
Results First Posted: August 24, 2021
Last Update Posted: August 24, 2021
Last Verified: July 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Jay F. Piccirillo, MD, Washington University School of Medicine:
Epistaxis
Additional relevant MeSH terms:
Layout table for MeSH terms
Epistaxis
Telangiectasis
Telangiectasia, Hereditary Hemorrhagic
Vascular Diseases
Cardiovascular Diseases
Nose Diseases
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Hemorrhage
Pathologic Processes
Signs and Symptoms, Respiratory
Hemostatic Disorders
Hemorrhagic Disorders
Hematologic Diseases
Vascular Malformations
Cardiovascular Abnormalities
Congenital Abnormalities
Timolol
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Antihypertensive Agents