Hereditary Hemorrhagic TelangiectasiaPhase 2ETIC-HHTNCT04139018
Timolol Gel for Epistaxis in Hereditary Hemorrhagic Telangiectasia
A Phase 2 study testing Timolol Gel in people with Hereditary Hemorrhagic Telangiectasia, run by Washington University School of Medicine at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Hereditary Hemorrhagic Telangiectasia
- What is being tested?
- Timolol Gel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Oct 2019to 20 May 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
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- 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)
- 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
- Patients currently treated or who plan to initiate treatment with β-blockers
- Use of any anti-angiogenic medication in the last month prior to recruitment, including bevacizumab, pazopanib, thalidomide, or lenalidomide
- Illicit drug use, except marijuana
- Known pheochromocytoma
- Use of anticoagulants, antiplatelet, or fibrinolytic therapies within the last month prior to recruitment, except for low-dose (81 mg or less) of aspirin
- Pregnancy or planned pregnancy in the next 6 months or currently breastfeeding
- Inability to read or understand English
- Inability to complete 8 weeks of therapy for any reason
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Efficacy of a Timolol Gel in the Care for Epistaxis in Patients With Hereditary Hemorrhagic Telangiectasia: A Double-Blinded, Randomized Controlled Trial
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.
Read the 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.
- Conditions
- Hereditary Hemorrhagic Telangiectasia
- Being tested
- Timolol Gel, Placebo Gel
- Keywords
- Epistaxis
- Medical subject headings
- Telangiectasia, Hereditary Hemorrhagic, Epistaxis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Timolol GelDrug
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 GelDrug
Placebo gel is prepared with poloxamers and no active ingredients.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Timolol Gel |
| Placebo Gel Arm | Placebo comparator | Participants in the placebo gel arm will receive the gel itself with no active medication. Receives: Drug: Placebo Gel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to 8-week follow-up
Secondary outcomes (1)
Number of Participants With Improved Response on Clinical Global Impression - Improvement (CGI-I) Scale
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."
Measured: Scores at 8-week follow-up only
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2019
- Study start20 Oct 2019
- Primary completion20 May 2020
- Study completion20 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hereditary Hemorrhagic TelangiectasiaStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jay F. Piccirillo, MD, Washington University School of Medicine
- Investigators
- Jay F Piccirillo, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04139018
- Sponsor's protocol ID
- 201908160
- Acronym
- ETIC-HHT
- Status last verified
- Jul 2021
- First submitted
- 23 Oct 2019
- Last updated
- 24 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 32940653
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of a Timolol Gel in the Care for Epistaxis in Patients With Hereditary Hemorrhagic Telangiectasia: A Double-Blinded, Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04139018
- Acronym / sponsor ID
- ETIC-HHT / 201908160
- Conditions
- Hereditary Hemorrhagic Telangiectasia
- Keywords
- Epistaxis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- 20 Oct 2019 (actual)
- Primary completion
- 20 May 2020 (actual)
- Study completion
- 20 May 2020 (actual)
- First posted
- 25 Oct 2019 (actual)
- Results
- Posted 24 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Timolol Gel Arm | Experimental | Drug: Timolol GelParticipants 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. |
| Placebo Gel Arm | Placebo comparator | Drug: Placebo GelParticipants in the placebo gel arm will receive the gel itself with no active medication. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (23 listed)
- Contraindications for systemic β adrenergic blocker administration
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Timolol GelTimolol 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. | Drug | Timolol Gel Arm |
| Placebo GelPlacebo gel is prepared with poloxamers and no active ingredients. | Drug | Placebo Gel Arm |
Primary outcome
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.
1 secondary outcome
Number of Participants With Improved Response on Clinical Global Impression - Improvement (CGI-I) Scale
Time frame: Scores at 8-week follow-up only
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32940653Peterson 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jay F Piccirillo, MD principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Timolol Gel in people with Hereditary Hemorrhagic Telangiectasia, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Assisted Epistaxis Severity Scale (aESS) Score From Baseline at 8 Week Follow-up (time frame: Baseline to 8-week follow-up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04139018, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2021.