Hemorrhagic Hereditary Telangiectasia (HHT)Phase 2TACRONCT03152019
Efficacy and Safety of a 0.1% Tacrolimus Nasal Ointment as a Treatment for Epistaxis in Hemorrhagic Hereditary Telangiectasia (HHT)
A Phase 2 study testing Protopic® (Tacrolimus) 0.1% ointment in people with Hemorrhagic Hereditary Telangiectasia (HHT), run by Hospices Civils de Lyon at 3 sites in France.
Trial summary
The recognized manifestations of HHT are all due to abnormalities in vascular structure. Epistaxis due to telangiectases formation is spontaneous, very variable, recurrent in 90% of patients, and associated with severe anemia in 2-10%. They also significantly reduce quality of life. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hemorrhagic Hereditary Telangiectasia (HHT)
- What is being tested?
- Protopic® (Tacrolimus) 0.1% ointment
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 3 sitesFrance
- Study dates
- 22 May 2017to 8 Nov 2018
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years.
- Patients who have given their free, informed and signed consent.
- Patients affiliated to a social security scheme or similar.
- Patients monitored for clinically confirmed HHT (presence of at least 3 Curaçao criteria) and/or confirmed by molecular biology.
- Patient presenting nosebleeds with total duration > 30 minutes for 6 weeks prior to the time of inclusion justified by completed follow-up grids.
Who cannot join
- Women who are pregnant or nursing (lactating), women of child-bearing potential without reliable contraception.
- Patients not affiliated to a social security scheme.
- Patients who are protected adults under the terms of the law (French Public Health Code).
- Refusal to consent.
- Patients for whom the diagnosis of HHT has not been confirmed clinically and/or by molecular biology.
- Participation in another clinical trial which may interfere with the proposed trial (judgment of the investigator).
Show all 14Show fewer
- Patients who have undergone nasal surgery in the 6 weeks prior to inclusion.
- Known hypersensitivity to macrolides in general, to tacrolimus or to any of the excipients.
- Patient with an inherited skin barrier disease such as Netherton's syndrome, lamellar ichtyosis, generalized erythroderma, graft-versus-host skin disease, or suffering from generalized erythroderma.
- Patient with CYP3A4 inhibitors treatment, e.g. erythromycin, itraconazole, ketoconazole and diltiazem.
- Patients who have incompletely filled in the nosebleed grids in the 10 weeks preceding the treatment. If there is missing data for more than 7 days, the patient cannot be included.
- Patients who do not present nosebleeds with a total duration of > 30 minutes for 6 weeks prior to the time of inclusion.
- Patients with ongoing immunosuppressive treatment.
- Patients with known and symptomatic immune deficiency
Trial locations and contacts
3 sites in 1 country.
France3 sites
Hôpital Femme Mère Enfant
Bron
CHU Estaing
Clermont-Ferrand
CHU de Montpellier
Montpellier
About this study
Official title: Efficacy and Safety of a 0.1% Tacrolimus Nasal Ointment as a Treatment for Epistaxis in Hemorrhagic Hereditary Telangiectasia (HHT) - A Double Blind, Randomized, Placebo-controlled, Multicenter Trial
The recognized manifestations of HHT are all due to abnormalities in vascular structure. Epistaxis due to telangiectases formation is spontaneous, very variable, recurrent in 90% of patients, and associated with severe anemia in 2-10%. They also significantly reduce quality of life.
Improvement in epistaxis has been shown in HHT patients after a liver transplantation. It was hypothesized that the immunosuppressive treatment (FK506) used to prevent rejection may have an anti-angiogenic effect.
Read more
The results of Albiñana et al suggest that the mechanism of action of FK506 involves a partial correction of endoglin and ALK1 haplosufficiency, genes responsible for 90% of HHT case.
Tacrolimus ointment is available on the market for the treatment of eczema and can therefore readily be used as it is for nasal administration. Topical nasal administration of tacrolimus may be an easy local ENT treatment that is non-aggressive and results in little trauma for the patient in relation to other first line treatment possibilities.
The main objective of this trial is to evaluate, at 6 weeks after the end of the treatment, the efficacy on the duration of nosebleeds, of 6 weeks tacrolimus nasal ointment application, in patients with HHT complicated by nosebleeds (30 min/6 weeks). Secondary objectives are to evaluate the tolerance throughout the study, the efficacy on anemia and on clinical parameters (nosebleeds, quality of life, epistaxis severity score questionnaire and blood transfusions) and the systemic absorption of nasal administration.
This is a multicenter prospective and double blinded phase I/II trial. A total of 48 patients will be randomized versus placebo using an allocation ratio of 1:1. The ointment (Protopic® at 0.1% or placebo) will be self-administered by the patient with one administration in each nostril twice a day for 6 consecutive weeks.
- Being tested
- Protopic® (Tacrolimus) 0.1% ointment, Placebo
- Keywords
- Hemorrhagic Hereditary Telangiectasia (HHT), Antiangiogenic therapy, Tacrolimus
- Medical subject headings
- Telangiectasia, Hereditary Hemorrhagic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Protopic® (Tacrolimus) 0.1% ointmentDrug
About 0,1g of ointment is administered by the patient on nasal mucosa of each nostril twice a day for 6 weeks.
PlaceboDrug
About 0,1g of ointment is administered by the patient on nasal mucosa of each nostril twice a day for 6 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Protopic® 0.1% (Tacrolimus) ointment | Active comparator | Protopic® 0.1% ointment, packed in blinded tube of 30g. Receives: Drug: Protopic® (Tacrolimus) 0.1% ointment |
| Placebo ointment | Placebo comparator | Same formulation as the Protopic® 0.1% ointment but without tacrolimus, packed in blinded tube of 30g. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Patients Experiencing an Improvement in Their Nosebleeds
Efficacy of tacrolimus nasal ointment on nosebleeds when administered for 6 weeks
Measured: up to 12 weeks
Secondary outcomes (9)
Adverse Events
Tolerance will be evaluated by recording adverse reactions and adverse events during the treatment period and the follow up period and by clinical examinations during the follow-up period.
Measured: up to 12 weeks
Number of Epistaxis
Evaluate efficacy on clinical criteria : epistaxis frequency before and after treatment.
Measured: up to 12 weeks
Epistaxis Duration
To evaluate efficacy of tacrolimus nasal ointment on duration of nosebleeds before and after treatment.
Measured: up to 12 weeks
Hemoglobin Level
before and after treatment.
Measured: up to 12 weeks
Ferritin Level
before and after treatment.
Measured: up to 12 weeks
Quality of Life Assessed by SF36 Questionnaire
To evaluate efficacy on quality of life with SF36 before and after treatment
Measured: up to 12 weeks
Severity Epistaxis Score Assessed by ESS Questionnaire
To evaluate efficacy on severity epistaxis score with ESS before and after treatment.
Measured: up to 12 weeks
The Percentage of Patient With Tacrolimus Detection in the Blood
To evaluate systemic absorption after tacrolimus nasal administrations.
Measured: up to 6 weeks
the Level of Exposure of Patient With Tacrolimus Detection in the Blood.
To evaluate systemic absorption after tacrolimus nasal administrations.
Measured: up to 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2017
- Study start22 May 2017
- Primary completion8 Nov 2018
- Study completion8 Nov 2018
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.
- Other trials for Hemorrhagic Hereditary Telangiectasia (HHT)Studies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sophie DUPUIS-GIROD, Principal investigator, Hospices Civils de Lyon Centre de Référence pour la maladie de Rendu-Osler Service de génétique Clinique Bâtiment A1 - HFMESophie DUPUIS-GIROD, Principal investigator, Hospices Civils de Lyon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03152019
- Sponsor's protocol ID
- 69HCL16_0705
- Other IDs
- 2017-000085-30, 2017
- Acronym
- TACRO
- Status last verified
- Jul 2019
- First submitted
- 11 May 2017
- Last updated
- 1 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of a 0.1% Tacrolimus Nasal Ointment as a Treatment for Epistaxis in Hemorrhagic Hereditary Telangiectasia (HHT) - A Double Blind, Randomized, Placebo-controlled, Multicenter Trial
- ClinicalTrials.gov ID
- NCT03152019
- Acronym / sponsor ID
- TACRO / 69HCL16_0705
- Keywords
- Hemorrhagic Hereditary Telangiectasia (HHT), Antiangiogenic therapy, Tacrolimus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 22 May 2017 (actual)
- Primary completion
- 8 Nov 2018 (actual)
- Study completion
- 8 Nov 2018 (actual)
- First posted
- 12 May 2017 (actual)
- Results
- Posted 1 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The recognized manifestations of HHT are all due to abnormalities in vascular structure. Epistaxis due to telangiectases formation is spontaneous, very variable, recurrent in 90% of patients, and associated with severe anemia in 2-10%. They also significantly reduce quality of life.
Improvement in epistaxis has been shown in HHT patients after a liver transplantation. It was hypothesized that the immunosuppressive treatment (FK506) used to prevent rejection may have an anti-angiogenic effect.
The results of Albiñana et al suggest that the mechanism of action of FK506 involves a partial correction of endoglin and ALK1 haplosufficiency, genes responsible for 90% of HHT case.
Tacrolimus ointment is available on the market for the treatment of eczema and can therefore readily be used as it is for nasal administration. Topical nasal administration of tacrolimus may be an easy local ENT treatment that is non-aggressive and results in little trauma for the patient in relation to other first line treatment possibilities.
The main objective of this trial is to evaluate, at 6 weeks after the end of the treatment, the efficacy on the duration of nosebleeds, of 6 weeks tacrolimus nasal ointment application, in patients with HHT complicated by nosebleeds (30 min/6 weeks). Secondary objectives are to evaluate the tolerance throughout the study, the efficacy on anemia and on clinical parameters (nosebleeds, quality of life, epistaxis severity score questionnaire and blood transfusions) and the systemic absorption of nasal administration.
This is a multicenter prospective and double blinded phase I/II trial. A total of 48 patients will be randomized versus placebo using an allocation ratio of 1:1. The ointment (Protopic® at 0.1% or placebo) will be self-administered by the patient with one administration in each nostril twice a day for 6 consecutive weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Protopic® 0.1% (Tacrolimus) ointment | Active comparator | Drug: Protopic® (Tacrolimus) 0.1% ointmentProtopic® 0.1% ointment, packed in blinded tube of 30g. |
| Placebo ointment | Placebo comparator | Drug: PlaceboSame formulation as the Protopic® 0.1% ointment but without tacrolimus, packed in blinded tube of 30g. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age ≥ 18 years.
- Patients who have given their free, informed and signed consent.
- Patients affiliated to a social security scheme or similar.
- Patients monitored for clinically confirmed HHT (presence of at least 3 Curaçao criteria) and/or confirmed by molecular biology.
- Patient presenting nosebleeds with total duration > 30 minutes for 6 weeks prior to the time of inclusion justified by completed follow-up grids.
Key exclusion criteria (14 listed)
- Women who are pregnant or nursing (lactating), women of child-bearing potential without reliable contraception.
- Patients not affiliated to a social security scheme.
- Patients who are protected adults under the terms of the law (French Public Health Code).
- Refusal to consent.
- Patients for whom the diagnosis of HHT has not been confirmed clinically and/or by molecular biology.
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 |
|---|---|---|
| Protopic® (Tacrolimus) 0.1% ointmentAbout 0,1g of ointment is administered by the patient on nasal mucosa of each nostril twice a day for 6 weeks. | Drug | Protopic® 0.1% (Tacrolimus) ointment |
| PlaceboAbout 0,1g of ointment is administered by the patient on nasal mucosa of each nostril twice a day for 6 weeks. | Drug | Placebo ointment |
Primary outcome
Percentage of Patients Experiencing an Improvement in Their Nosebleeds
Time frame: up to 12 weeks
Efficacy of tacrolimus nasal ointment on nosebleeds when administered for 6 weeks
9 secondary outcomes
Adverse Events
Time frame: up to 12 weeks
Number of Epistaxis
Time frame: up to 12 weeks
Epistaxis Duration
Time frame: up to 12 weeks
Hemoglobin Level
Time frame: up to 12 weeks
Ferritin Level
Time frame: up to 12 weeks
Quality of Life Assessed by SF36 Questionnaire
Time frame: up to 12 weeks
Severity Epistaxis Score Assessed by ESS Questionnaire
Time frame: up to 12 weeks
The Percentage of Patient With Tacrolimus Detection in the Blood
Time frame: up to 6 weeks
the Level of Exposure of Patient With Tacrolimus Detection in the Blood.
Time frame: up to 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Related InfoLink provided by the sponsor.
Related trials for Hemorrhagic Hereditary Telangiectasia (HHT)
RecruitingPhase 1/2
Harmony-HHT: ATV-1601 in Participants With Hereditary Hemorrhagic Telangiectasia (HHT)
Hereditary Hemorrhagic Telangiectasia (HHT), Osler Weber Rendu Disease
Not yet recruitingPhase 1
Topical TOR-582 Treatment of Epistaxis in HHT
Hereditary Hemorrhagic Telangiectasia (HHT), Epistaxis
RecruitingObservational study
Quality of Life in Pediatric Participants With HHT
Hereditary Haemorrhagic Telangiectasia (HHT)
Not yet recruitingObservational study
Prevalence of Obstructive Sleep Apnea in HHT and HHT-specific Challenges in OSA-therapy - a Retrospective Cohort Study
Hereditary Hemorrhagic Telangiectasia (HHT), Obstructive Sleep Apnea (OSA)
Not yet recruitingPhase 1
Phase 1b Study of TX002100 in Participants With Hematologic Support-Dependent Hereditary Hemorrhagic Telangiectasia (HHT)
Hereditary Hemorrhagic Telangiectasia (HHT)
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.
Sophie DUPUIS-GIROD principal investigator
Hospices Civils de Lyon Centre de Référence pour la maladie de Rendu-Osler Service de génétique Clinique Bâtiment A1 - HFME
Sophie DUPUIS-GIROD principal investigator
Hospices Civils de Lyon
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Protopic® (Tacrolimus) 0.1% ointment in people with Hemorrhagic Hereditary Telangiectasia (HHT), run by Hospices Civils de Lyon at 3 sites in France.
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 14 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 1 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in France. 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 1 Jul 2020). 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?
Percentage of Patients Experiencing an Improvement in Their Nosebleeds (time frame: up to 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Jul 2020; AzTrials last refreshed its copy on 8 Nov 2026.