Background Tinnitus is associated with a variety of etiologies, phenotypes, and underlying pathophysiological mechanisms, and available treatments have limited efficacy. A combination of treatments, addressing various aspects of tinnitus, might provide a viable and superior treatment strategy.

Methods In this multicenter, parallel-arm, randomized controlled clinical trial, patients with chronic subjective tinnitus were randomly assigned to single or combination treatment of 12 weeks each. Cognitive-behavioral therapy, hearing aids, structured counseling and sound therapy were administered either alone or as a combination of two treatments resulting in 10 treatment arms. The primary endpoint was the difference in the change from baseline to week 12 in the total score of the Tinnitus Handicap Inventory between single and combination treatments.

Results Out of 461 enrolled patients 230 were assigned to single and 231 to combination treatment. Least-squares mean changes from baseline to week 12 were −11.7 for single (95% confidence interval [CI], −14.4 to −9.0) and −14.9 for combination treatments (95% CI, −17.7 to −12.1), with a significant between-group difference (p=0.034). Sound therapy alone had the lowest effect size. In contrast, cognitive-behavioral therapy and hearing aids alone had large effect sizes, which could not be further increased by combination treatment.

Conclusions In this trial involving patients with chronic tinnitus, all treatment arms showed improvement in THI scores from baseline to week 12. No clear synergistic effect was observed when combining treatments, but rather a compensatory effect, where a more effective treatment offsets the clinical effects of a less effective treatment.

(Funded by the EU, number: 848261, ClinicalTrials.gov number: NCT04663828)

The authors have declared no competing interest.

NCT04663828

https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-021-05835-z

https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-023-07303-2

This clinical trial received funding from the European Unions Horizon 2020 Research and Innovation Program (grant agreement number 848261)

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The study was independently approved by the following ethics committees: University of Regensburg, Regensburg, Germany (combined ethical approval for clinical sites Berlin and Regensburg); Katholieke Universiteit Leuven, Leuven, Belgium; Ethniko Kai Kapodistriako Panepistimo Athinon, Athens, Greece; Hospital Universitario Virgen de las Nieves/ Hospital Clinico Universitario San Cecilio, Granada, Spain.

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