5.1 Study hypothesisThe primary study hypothesis states that oral treatment with itraconazole will reduce the epistaxis severity score (ESS) due to the anti-angiogenic effects of itraconazole.5.2 Research question and primary outcomeWhat is the…
ID
Source
Brief title
Condition
- Cardiac and vascular disorders congenital
- Skin vascular abnormalities
- Vascular haemorrhagic disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome of this study is the difference of epistaxis severity score
between the baseline and at the end of the trial.
Secondary outcome
Safety of itraconazole, side-effects, adverse events
Difference in monthly epistaxis severity measured with:
- Monthly number of episodes;
- Monthly duration;
- Monthly intensity;
- VAS score of epistaxis frequency, duration and intensity.
Difference in biochemical blood values: Hb and ferritin between baseline and
the end of the study.
Difference in quality of life with SF-36 between baseline and end of the study
Background summary
Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant inherited
disease characterized by mucocutaneous telangiectasias and arteriovenous
malformations (AVMs). The exact pathophysiology is still unclear, however
elevated levels of vascular endothelial growth factor (VEGF) are believed to
play an important role in pathogenesis of HHT. The majority of HHT patients
suffers from spontaneous recurrent epistaxis (nose bleeding) from the nasal
telangiectasias. In addition, epistaxis in HHT patients can significantly
decrease the quality of life. Treatment of epistaxis in HHT patients is
difficult since standard measurements rarely have a sustained effect. In some
cases, systemic therapies with either thalidomide or VEGF-inhibiting
bevacizumab may be required to decrease epistaxis severity. However, neither of
the systematic treatments are ideal for epistaxis treatment due to the severe
side-effects of thalidomide and intravenous administration and high costs of
bevacizumab. Recently it has been discovered that besides antifungal
properties, itraconazole inhibits angiogenesis by inhibiting the
VEGF-receptors. Itraconazole has already been used for its anti-angiogenic
properties in human cancer studies and has shown great potential. Based on this
evidence, the fact that VEGF is elevated in HHT patients and that VEGF
inhibition has shown to reduce epistaxis, the antiangiogenic effects of
itraconazole could potentially reduce epistaxis severity in HHT patients. In
addition, itraconazole is an affordable, unpatented and generally well
tolerated drug. Therefore itraconazole could potentially be a new, viable
treatment option for severe epistaxis in HHT patients.
Study objective
5.1 Study hypothesis
The primary study hypothesis states that oral treatment with itraconazole will
reduce the epistaxis severity score (ESS) due to the anti-angiogenic effects of
itraconazole.
5.2 Research question and primary outcome
What is the effect of oral itraconazole treatment on the epistaxis severity
score (ESS) in patients with moderate-severe epistaxis and hereditary
hemorrhagic telangiectasia?
5.3 Secondary outcome(s)
- Safety of oral itraconazole in HHT patients with epistaxis. What the
side-effects and (serious) adverse events?
- 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.
- Difference in quality of life in HHT patients with epistaxis following
treatment.
- Effects of itraconazole on other HHT associated symptoms such as
gastro-intestinal blood loss and presence of telangiectasias.
Study design
Open label, single-center, uncontrolled pilot-study
Intervention
daily 200 mg itraconazole for 16 weeks (4 months)
Study burden and risks
The burden consist of 4 extra visits, blood samples (5 times), recording a
epistaxis diary and two times questionnaires (SF*36). There is a risk for the
known side*effects of the itraconazole. The potential benefit for participating
patients is that itraconazole may reduce the severity of epistaxis.
Koekoekslaan 1
Nieuwegein 3435CM
NL
Koekoekslaan 1
Nieuwegein 3435CM
NL
Listed location countries
Age
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).
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 drugscontraindicated when using itraconazole (see protocol chapter 14.1 section G of the study protocol for a full list)
8. Patients who do not understand English or Dutch language sufficiently enough;
9. Patients who refuse informed consent.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-003272-31-NL |
| CCMO | NL62902.100.17 |