Jorge Piano Simoes, Stefan Schoisswohl, Winfried Schlee, Laura Basso, Alberto Bernal-Robledano, Benjamin Boecking, Rilana Cima, Sam Denys, Milena Engelke, Alba Escalera-Balsera, Alvaro Gallego-Martinez, Silvano Gallus, Dimitris Kikidis, Jose A. López-Escámez, Steven C. Marcrum, Nikolaos Markatos, Juan Martin-Lagos, Marta Martinez-Martinez, Birgit Mazurek, Evgenia Vassou, Carlotta Micaela Jarach, Nicolas Mueller-Locatelli, Patrick Neff, Uli Niemann, Hafez Kader Omar, Clara Puga, Miro Schleicher, Vishnu Unnikrishnan, Patricia Perez-Carpena, Rüdiger Pryss, Paula Robles-Bolivar, Matthias Rose, Martin Schecklmann, Tabea Schiele, Johannes Schobel, Myra Spiliopoulou, Sabine Stark, Carsten Vogel, Nina Wunder, Zoi Zachou, and Berthold Langguth
Abstract Background Tinnitus is a leading cause of disease burden globally. Several therapeutic strategies are recommended in guidelines for the reduction of tinnitus distress; however, little is known about the potentially increased effectiveness of a combination of treatments and personalized treatments for each tinnitus patient. Methods Within the Unification of Treatments and Interventions for Tinnitus Patients project, a multicenter, randomized clinical trial is conducted with the aim to compare the effectiveness of single treatments and combined treatments on tinnitus distress (UNITI-RCT). Five different tinnitus centers across Europe aim to treat chronic tinnitus patients with either cognitive behavioral therapy, sound therapy, structured counseling, or hearing aids alone, or with a combination of two of these treatments, resulting in four treatment arms with single treatment and six treatment arms with combinational treatment. This statistical analysis plan describes the statistical methods to be deployed in the UNITI-RCT. Discussion The UNITI-RCT trial will provide important evidence about whether a combination of treatments is superior to a single treatment alone in the management of chronic tinnitus patients. This pre-specified statistical analysis plan details the methodology for the analysis of the UNITI trial results. Trial registration ClinicalTrials.gov NCT04663828 . The trial is ongoing. Date of registration: December 11, 2020. All patients that finished their treatment before 19 December 2022 are included in the main RCT analysis.