Gastrointestinal bleeding and epistaxis caused by hereditary hemorrhagic telangiectasia. Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant inherited disease characterized by mucocutaneous telangiectasis. Telangiectasis predominantly observed in the nasal mucosa and gut, and are abnormal, thin walled blood vessel that can easily rupture leading to hemorrhage. MedDRA version: 20.0 Level: LLT Classification code 10038554
Conditions
Interventions
Trade Name: Tacrolimus (Advagraf)
Product Name: Tacrolimus (Advagraf)
Product Code: EMEA/H/C/000712
Pharmaceutical Form: Capsule
Sponsors
St. Antonius Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patients with HHT: o Definite HHT according to the Curacao criteria (3 positive criteria or more) AND/OR o Genetically confirmed HHT • Suffering from epistaxis at least on average of 4 days per week or documented gastrointestinal teleangiectasis by endoscopy with suspicion of bleeding; • In the last six months suffering from anemia, iron deficiency or use iron treatment or blood transfusions; • Failure or partial failure of local treatment with systemic treatment indicated by ENT specialist or gastroenterologist; • 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 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: • Hypersensitivity or allergy for tacrolimus • Patients with a severe disease with a life-expectancy <1 year; • Women that are pregnant, nursing, have a pregnancy wish in the study period or who use anticonception inadequately; • Patients currently receiving chemotherapy; • Patients receiving drugs that are contraindicated when using tacrolimus (see chapter 14.1, section G). • Patients who do not understand English or Dutch language sufficiently enough; • Patients who refuse informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy and safety of oral tacrolimus in reducing bleeding severity in HHT patients with severe epistaxis and/or gastrointestinal bleeding. The primary objective is to measure the hemoglobin level at the beginning and during the trial.;Secondary Objective: As secondary outcomes, reduction in the epistaxis severity score (ESS), quality of life, the safety (side-effects, (s)AEs) of the therapy, and difference in monthly epistaxis duration, epistaxis frequency, the use of iron infusions, blood transfusions, mean ferritin will be evaluated after 20 weeks of therapy compared to the parameters at baseline. ;Primary end point(s): The primary outcome of this study is the difference in hemoglobin levels at the baseline compared to that at the end of the trial;Timepoint(s) of evaluation of this end point: The primary end point will be evaluated at the baseline and at the end of the trial. The difference will be calculated | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Difference in monthly epistaxis severity measured with: o Epistaxis severity score (ESS); o Monthly number of episodes; o Monthly duration; o Monthly intensity; o VAS score of epistaxis. • Difference in biochemical blood values: Hb and ferritin. • Differences in required number of blood transfusions and iron infusions. • Difference in quality of life with SF-36 and fatigue complaints (MFI-20) between baseline and end of the study. ;Timepoint(s) of evaluation of this end point: All the secondary end points will be evaluated at the baseline and at the end of the trial. The only exception is the difference in required number of blood transfusions and iron infusions. We will compare the number of required number of blood transfusions and iron infusions during the trial (20 weeks) and to the same period prior to the trial | — |
Countries
Netherlands
Contacts
Public ContactS. Kroon
St. Antonius Hospital
Outcome results
None listed