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Hereditary hemorrhagic telangiectasia (HHT) is a vascular bleeding disorder characterized by mucocutaneous telangiectasias and visceral arteriovenous malformations. A frequently debilitating symptom is spontaneous recurrent epistaxis. To evaluate whether doxycycline therapy improves epistaxis in HHT by using a prospective, randomized, placebo-controlled crossover study design. Twenty-two eligible patients between December 2017 and July 2020 at a single center were randomized to one of two study arms doxycycline treatment followed by plac