Hemorrhagic Hereditary Telangiectasia (HHT) Clinical Trial
Official title:
Efficacy and Safety of a 0.1% Tacrolimus Nasal Ointment as a Treatment for Epistaxis in Hemorrhagic Hereditary Telangiectasia (HHT) - A Double Blind, Randomized, Placebo-controlled, Multicenter Trial
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.
n/a