TIMolol nasal spray as a treatment for epistaxis in hereditary hemorrhagic telangiectasia (HHT) – Study protocol of the prospective, randomized, double-blind, controlled cross-over TIM-HHT trial

Article type: Research Article

Authors: Andorfer, K.E.C.^{a; *} | Seebauer, C.T.^a | Koller, M.^b | Zeman, F.^b | Berneburg, M.^c | Fischer, R.^a | Vielsmeier, V.^a | Bohr, C.^a | Kühnel, T.S.^a

Affiliations: [a] Department of Otorhinolaryngology, University Hospital Regensburg, Regensburg, Germany | [b] Center for Clinical Studies, University Hospital Regensburg, Regensburg, Germany | [c] Department of Dermatology and Center for Orphan Diseases, University Hospital Regensburg, Regensburg, Germany

Correspondence: [*] Corresponding author: Kornelia Andorfer, MD., Department of Otorhinolaryngology, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg D-93053, Germany. Phone: +49 941 944 9410; Fax: +49 941 944 9405, E-mail: [email protected].

Abstract: BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is an inherited orphan disease, in which the absence of capillary beds between arterioles and venules lead to arteriovenous shunts. Epistaxis is the core symptom. Several case reports have described the nonselective beta-adrenergic receptor antagonist timolol as a successful treatment method of nosebleeds due in HHT patients. OBJECTIVE: TIM-HHT is a single-site, prospective, randomized, placebo-controlled, double-blind, cross-over study to investigate whether the efficacy of standard laser treatment of epistaxis in HHT patients can be increased by the additional use of timolol nasal spray (1 mg/d). METHODS: Twenty patients will be randomly allocated to one of two treatment sequences. Primary outcome is the severity of epistaxis determined by the Epistaxis Severity Score (ESS). Secondary outcomes are subjective satisfaction, quality of life, as well as the hemoglobin, ferritin, and transferrin levels of the participating patients. Safety outcome is assessed by means of pulse, blood pressure, and adverse events. CONCLUSION: TIM-HHT will evaluate the efficacy and safety of timolol as an additional treatment of epistaxis in HHT patients in a three-month trial period. Benzalkonium chloride is used as a placebo, which has no documented positive effect on the nasal mucosa and hence on epistaxis in HHT patients (in contrast to saline). TRIAL REGISTRATION: German Clinical Trials Register (DRKS), DRKS00020994. Registered on 10 March 2020

Keywords: Timolol, nasal sprays, HHT, hereditary hemorrhagic telangiectasia, Osler, rare disease, epistaxis

DOI: 10.3233/CH-211253

Journal: Clinical Hemorheology and Microcirculation, vol. 80, no. 3, pp. 307-315, 2022