Efficacy and Safety of a 0.1% Tacrolimus Nasal Ointment as a Treatment for Epistaxis in Hemorrhagic Hereditary Telangiectasia (HHT)

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-05-22

Study Completion Date

2018-11-08

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Timolol Gel for Epistaxis in Hereditary Hemorrhagic Telangiectasia

NCT04139018

Hereditary Hemorrhagic Telangiectasia

COMPLETED PHASE2

North American Study of Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT)

NCT01408030

Telangiectasia, Hereditary Hemorrhagic Epistaxis

COMPLETED PHASE2

NOrth American Study for the Treatment of Recurrent epIstaxis With DoxycycLine: The NOSTRIL Trial

NCT04167085

Epistaxis

COMPLETED PHASE4

The Effect of Intranasal Vasoconstrictor Medications on Hemodynamic Parameters: A Randomized Double-blind, Placebo-controlled Trial.

NCT02285634

Epistaxis Blood Pressure

COMPLETED NA

Propranolol Administration in Pediatric Patients With Recurrent Respiratory Papillomatosis

NCT01058317

Recurrent Respiratory Papillomatosis

WITHDRAWN PHASE2/PHASE3

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Hemorrhagic Hereditary Telangiectasia (HHT)

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Protopic® 0.1% (Tacrolimus) ointment

Protopic® 0.1% ointment, packed in blinded tube of 30g.

Group Type ACTIVE_COMPARATOR

Protopic® (Tacrolimus) 0.1% ointment

Intervention Type DRUG

About 0,1g of ointment is administered by the patient on nasal mucosa of each nostril twice a day for 6 weeks.

Placebo ointment

Same formulation as the Protopic® 0.1% ointment but without tacrolimus, packed in blinded tube of 30g.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

About 0,1g of ointment is administered by the patient on nasal mucosa of each nostril twice a day for 6 weeks.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Protopic® (Tacrolimus) 0.1% ointment

About 0,1g of ointment is administered by the patient on nasal mucosa of each nostril twice a day for 6 weeks.

Intervention Type DRUG

Placebo

About 0,1g of ointment is administered by the patient on nasal mucosa of each nostril twice a day for 6 weeks.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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.

Exclusion Criteria

* 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).
* 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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No