Hereditary hemorrhagic telangiectasia is a rare but ubiquitous
genetic disease.
Epistaxis is the most frequent and life-threatening manifestation and
tacrolimus, an
immunosuppressive agent, appears to be an interesting new treatment option because of its anti-angiogenic properties. Our objective was to evaluate, six weeks after the end of the treatment, the efficacy on the duration of
nosebleeds of
tacrolimus nasal
ointment, administered for six weeks to patients with
hereditary hemorrhagic telangiectasia complicated by
nosebleeds, and we performed a prospective, multicenter, randomized, placebo-controlled, double-blinded, ratio 1:1 phase II study. Patients were recruited from three French
Hereditary Hemorrhagic Telangiectasia (HHT) centers between May 2017 and August 2018, with a six-week follow-up, and we included people aged over 18 years, diagnosed with
hereditary hemorrhagic telangiectasia and
epistaxis (total duration > 30 min/6 weeks prior to inclusion).
Tacrolimus ointment 0.1% was self-administered by the patients twice daily. About 0.1 g of product was to be administered in each nostril with a cotton swab. A total of 50 patients was randomized and treated. Mean
epistaxis duration before and
after treatment in the
tacrolimus group were 324.64 and 249.14 min, respectively, and in the placebo group 224.69 and 188.14 min, respectively.
Epistaxis duration improved in both groups, with no significant difference in our main objective comparing
epistaxis before and
after treatment (p = 0.77); however, there was a significant difference in evolution when comparing
epistaxis before and during treatment (p = 0.04). Toxicity was low and no severe adverse events were reported. In conclusion,
tacrolimus nasal
ointment, administered for six weeks, did not improve
epistaxis in HHT patients after the end of the treatment. However, the good tolerance, associated with a significant improvement in
epistaxis duration during treatment, encouraged us to perform a phase 3 trial on a larger patient population with a main outcome of
epistaxis duration during treatment and a longer treatment time.