Design and Baseline Characteristics of CONCORD, a Trial of Novel Therapies for Depression in CKD

Background Major depressive disorder (MDD) is prevalent in people with CKD and associated with adverse outcomes. Traditional pharmacologic and non-pharmacologic treatments as monotherapy have demonstrated limited efficacy for MDD, necessitating studies of other treatment options. Methods The Combination of Novel Therapies for Chronic Kidney Disease Comorbid Depression Trial (CONCORD) is a multi-center randomized placebo-controlled trial to evaluate two distinct treatment strategies compared to control in participants with CKD G3b-5 and MDD, beginning with 8 weeks of monotherapy with single-blind behavioral activation teletherapy (BAT) plus double-blind placebo, or double-blind bupropion-SR once daily plus single-blind attention control clinical management (CM). The assigned monotherapy is continued for another 8 weeks if depression remits. If depression fails to remit, the participant will receive combination therapy with bupropion and BAT for 8 weeks. The control arm includes parallel frequency-matched single-blind CM plus double-blind placebo for 16 weeks. The primary outcome is improvement in depression severity from baseline to 16 weeks. Secondary outcomes include safety and tolerability. Association with inflammation and effect on patient-reported outcomes will also be explored. Results Two-hundred and two patients were randomized across 3 U.S. sites. Mean (SD) age was 56 (12) years and mean eGFR 24.6 (10.9) mL/min/1.73 m 2 . Forty-two percent were women, 29.7% African American, and 29.4% Hispanic persons. Percentages with CKD G3b, G4, G5, and G5D were 36.6%, 43.1%, 10.9%, and 9.4%. Conclusion CONCORD will provide evidence for the effectiveness of bupropion, BAT, and combination therapy for depression in adults with CKD, which can inform changes in clinical practice.