Itraconazole as treatment for severe nose bleeding in patients with hereditary hemorrhagic telangiectasia

• Register: EUCTR
• Last refreshed on: 5 June 2018
• Main ID: EUCTR2017-003272-31-NL
• Date of registration: 11/01/2018
• Prospective Registration: Yes
• Primary sponsor: St. Antonius Ziekenhuis
• Public title: Itraconazole as treatment for severe nose bleeding in patients with hereditary hemorrhagic telangiectasia
• Scientific title: Efficacy and safety of oral itraconazole in the reduction of epistaxis severity in hereditary hemorrhagic telangiectasia - Itraconazole for epistaxis in HHT patients
• Date of first enrolment: 18/05/2018
• Target sample size: 25
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-003272-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Netherlands

Contacts

• Name: Central study coordinator
• Affiliation: St. Antonius Ziekenhuis

• Name: Central study coordinator
• Affiliation: St. Antonius Ziekenhuis

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients with HHT: Definite HHT according to the Curacao criteria (3 positive criteria or more) AND/OR genetically confirmed HHT
2. Suffering from epistaxis at least on average of 4 days per week;
3. In the last six months suffering from anemia or iron deficiency or in last twelve months use iron treatment or blood transfusions;
4. Failure or partial failure of local treatment with systemic treatment indicated by ENT specialist;
5. Adult (18 years or older at time of inclusion).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 12
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 13

Exclusion criteria:
1. Patients with any history of ventricular cardiac dysfunction;
2. Patients with elevated liver enzymes or any pre-existing liver disease or a history with known liver toxicity caused by medication;
3. Hypersensitivity or allergy for azole antifungal drugs;
4. Patients with a severe disease with a life-expectancy <1 year;
5. Women that are pregnant, nursing, have a pregnancy wish in the study period or who use anticonception inadequately;
6. Patients currently receiving chemotherapy;
7. Patients receiving drugs that are metabolized by CYP3A: that prolongate QT-interval (mizolastine, pimozide, sertindole of quinidine), orally administered midazolam, statins (simvastatin, atorvastatin), alkaloids (ergotamine), eletriptan, or drugs that induce CYP3A4 (rifampicin, rifabutin, phenytoin, carbamazepine, phenobarbital or St John's wort (Hypericum perforatum));
8. Patients who do not understand English or Dutch language sufficiently enough;
9. Patients who refuse informed consent.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Severe epistaxis in patients with Hereditary Hemorrhagic Telangiectasia also known as Rendu-Osler-Weber disease
MedDRA version: 20.0 Level: LLT Classification code 10031132 Term: Osler-Weber-Rendu disease System Organ Class: 100000004850
MedDRA version: 20.0 Level: LLT Classification code 10038554 Term: Rendu-Osler-Weber syndrome System Organ Class: 100000004850

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Intervention(s)

Trade Name: Sporanox
Product Name: Itraconazole
Pharmaceutical Form: Capsule

Primary Outcome(s)

Main Objective: Study hypothesis: The primary study hypothesis states that oral treatment with itraconazole will reduce the epistaxis severity and frequency due to the anti-angiogenic effects of itraconazole. Study objective: To assess the efficacy and safety of oral itraconazole in HHT patients with severe epistaxis

Primary end point(s): The primary end point used in this study is the epistaxis severity score (ESS)

Secondary Objective: Difference in monthly epistaxis duration and frequency after treatment compared to baseline.
Difference in the mean hemoglobin (Hb) and ferritin levels in HHT patients with epistaxis after treatment compared to baseline.
Difference in quality of life in HHT patients with epistaxis following treatment after treatment compared to baseline.
Effects of itraconazole on other HHT associated symptoms such as gastro-intestinal blood loss and presence of telangiectasias after treatment compared to baseline.
Safety, side-effects and (serious) adverse events of oral itraconazole in HHT patients with epistaxis.
Long term efficacy of treatment at 1 and 3 months after itraconazole treatment has ended on the severity of epistaxis.

Timepoint(s) of evaluation of this end point: End point will be evaluated after 16 weeks of treatment

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: End point will be evaluated after 16 weeks of treatment

Secondary end point(s): The secondary end points in this study are safety of therapy, the frequency and number of monthly epistaxis measured with an epistaxis diary, hemoglobin levels, ferritin levels, and the quality of life measured with the Short-Form Questionnaire 36 (SF-36).

Secondary ID(s)

NL.EPITRAC.0107.17

Source(s) of Monetary Support

Stichting Wetenschappelijk Onderzoek Rendu Osler (SWORO)

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