E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe epistaxis in patients with Hereditary Hemorrhagic Telangiectasia also known as Rendu-Osler-Weber disease |
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E.1.1.1 | Medical condition in easily understood language |
Severe nose bleedings in patients with Hereditary hemorrhagic telangiectasia also known as Rendu-Osler-Weber disease |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10031132 |
E.1.2 | Term | Osler-Weber-Rendu disease |
E.1.2 | System Organ Class | 100000004850 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10038554 |
E.1.2 | Term | Rendu-Osler-Weber syndrome |
E.1.2 | System Organ Class | 100000004850 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
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.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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).
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end point used in this study is the epistaxis severity score (ESS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
End point will be evaluated after 16 weeks of treatment |
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E.5.2 | 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). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
End point will be evaluated after 16 weeks of treatment |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study is defined as the last patient’s last visit. In case the study is ended prematurely, the sponsor will notify the accredited METC and the competent authority within 15 days, including the reasons for the premature termination. Within one year after the end of the study, the investigator/sponsor will submit a final study report with the results of the study, including any publications/abstracts of the study, to the accredited METC and the Competent Authority. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |