Trial Outcomes & Findings for Timolol Gel for Epistaxis in Hereditary Hemorrhagic Telangiectasia (NCT NCT04139018)

Last Updated: 2021-08-24

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

27 participants

Primary outcome timeframe

Baseline to 8-week follow-up

Results posted on

2021-08-24

Participant Flow

Recruitment occurred from October 2019 through March 2020 at Washington University HHT Center of Excellence

272 participants total were assessed for eligibility; 245 met exclusion criteria

Participant milestones

Participant milestones
Measure	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. 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 Gel Arm Participants in the placebo gel arm will receive the gel itself with no active medication. Placebo Gel: Placebo gel is prepared with poloxamers and no active ingredients.
Overall Study STARTED	14	13
Overall Study COMPLETED	11	12
Overall Study NOT COMPLETED	3	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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. 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 Gel Arm Participants in the placebo gel arm will receive the gel itself with no active medication. Placebo Gel: Placebo gel is prepared with poloxamers and no active ingredients.
Overall Study Screen fail	1	0
Overall Study Withdrawal by Subject	2	0
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

Timolol Gel for Epistaxis in Hereditary Hemorrhagic Telangiectasia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Timolol Gel Arm n=14 Participants 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. 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 Gel Arm n=13 Participants Participants in the placebo gel arm will receive the gel itself with no active medication. Placebo Gel: Placebo gel is prepared with poloxamers and no active ingredients.	Total n=27 Participants Total of all reporting groups
Age, Continuous	58 years n=5 Participants	52 years n=7 Participants	55 years n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	4 Participants n=7 Participants	14 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	9 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	14 Participants n=5 Participants	11 Participants n=7 Participants	25 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	14 participants n=5 Participants	13 participants n=7 Participants	27 participants n=5 Participants
Hypertension	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Seasonal Allergies	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Comorbidity Status None	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Comorbidity Status Mild	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Comorbidity Status Moderate	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Comorbidity Status Severe	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Baseline Clinical Global Impression - Severity No Problem	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Baseline Clinical Global Impression - Severity Mild Problem	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Baseline Clinical Global Impression - Severity Moderate/Severe Problem	10 Participants n=5 Participants	5 Participants n=7 Participants	15 Participants n=5 Participants
Baseline Clinical Global Impression - Severity Problem as bad as it could be	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Baseline Clinical Global Impression - Severity Unknown	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 8-week follow-up

Population: Analysis was used with intention-to-treat principles, so all patients enrolled with baseline data were included. Note: the screen fail participant within the timolol gel arm had no baseline data say they were excluded from the analysis.

Outcome measures

Outcome measures
Measure	Timolol Gel Arm n=13 Participants 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. 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 Gel Arm n=13 Participants Participants in the placebo gel arm will receive the gel itself with no active medication. Placebo Gel: Placebo gel is prepared with poloxamers and no active ingredients.
Change in Assisted Epistaxis Severity Scale (aESS) Score From Baseline at 8 Week Follow-up	2.32 units on a scale Interval 0.22 to 5.97	1.96 units on a scale Interval -0.91 to 5.98

SECONDARY outcome

Timeframe: 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."

Outcome measures

Outcome measures
Measure	Timolol Gel Arm n=11 Participants 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. 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 Gel Arm n=12 Participants Participants in the placebo gel arm will receive the gel itself with no active medication. Placebo Gel: Placebo gel is prepared with poloxamers and no active ingredients.
Number of Participants With Improved Response on Clinical Global Impression - Improvement (CGI-I) Scale No Change	0 Participants	1 Participants
Number of Participants With Improved Response on Clinical Global Impression - Improvement (CGI-I) Scale Slightly Improved	4 Participants	3 Participants
Number of Participants With Improved Response on Clinical Global Impression - Improvement (CGI-I) Scale Much Improved	7 Participants	8 Participants

Adverse Events

Timolol Gel Arm

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo Gel Arm

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Timolol Gel Arm n=14 participants at risk 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. 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 Gel Arm n=13 participants at risk Participants in the placebo gel arm will receive the gel itself with no active medication. Placebo Gel: Placebo gel is prepared with poloxamers and no active ingredients.
Respiratory, thoracic and mediastinal disorders Shortness of breath	7.1% 1/14 • Adverse events collected throughout the whole duration of the study and assessed multiple times throughout a participant's 8 weeks of intervention.	0.00% 0/13 • Adverse events collected throughout the whole duration of the study and assessed multiple times throughout a participant's 8 weeks of intervention.
Vascular disorders Dizziness	7.1% 1/14 • Adverse events collected throughout the whole duration of the study and assessed multiple times throughout a participant's 8 weeks of intervention.	0.00% 0/13 • Adverse events collected throughout the whole duration of the study and assessed multiple times throughout a participant's 8 weeks of intervention.
General disorders Nasal congestion	21.4% 3/14 • Adverse events collected throughout the whole duration of the study and assessed multiple times throughout a participant's 8 weeks of intervention.	0.00% 0/13 • Adverse events collected throughout the whole duration of the study and assessed multiple times throughout a participant's 8 weeks of intervention.
General disorders Headache	7.1% 1/14 • Adverse events collected throughout the whole duration of the study and assessed multiple times throughout a participant's 8 weeks of intervention.	7.7% 1/13 • Adverse events collected throughout the whole duration of the study and assessed multiple times throughout a participant's 8 weeks of intervention.
General disorders Rhinorrhea	7.1% 1/14 • Adverse events collected throughout the whole duration of the study and assessed multiple times throughout a participant's 8 weeks of intervention.	0.00% 0/13 • Adverse events collected throughout the whole duration of the study and assessed multiple times throughout a participant's 8 weeks of intervention.
General disorders Nausea	7.1% 1/14 • Adverse events collected throughout the whole duration of the study and assessed multiple times throughout a participant's 8 weeks of intervention.	0.00% 0/13 • Adverse events collected throughout the whole duration of the study and assessed multiple times throughout a participant's 8 weeks of intervention.
General disorders Bad taste of medication	7.1% 1/14 • Adverse events collected throughout the whole duration of the study and assessed multiple times throughout a participant's 8 weeks of intervention.	0.00% 0/13 • Adverse events collected throughout the whole duration of the study and assessed multiple times throughout a participant's 8 weeks of intervention.
General disorders Sore throat	0.00% 0/14 • Adverse events collected throughout the whole duration of the study and assessed multiple times throughout a participant's 8 weeks of intervention.	7.7% 1/13 • Adverse events collected throughout the whole duration of the study and assessed multiple times throughout a participant's 8 weeks of intervention.
General disorders Irritation upon applying gel	0.00% 0/14 • Adverse events collected throughout the whole duration of the study and assessed multiple times throughout a participant's 8 weeks of intervention.	7.7% 1/13 • Adverse events collected throughout the whole duration of the study and assessed multiple times throughout a participant's 8 weeks of intervention.

Additional Information

Jay Piccirillo, M.D., Vice Chair for Research

Washington University School of Medicine Department of Otolaryngology - Head and Neck Surgery

Phone: 314-362-8641

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place