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

Major depressive disorder (MDD) is prevalent in patients with chronic kidney disease (CKD) and is associated with adverse outcomes. Traditional pharmacologic and nonpharmacologic treatments as monotherapy have shown limited efficacy for MDD, necessitating studies of other treatment options.

The Combination of Novel Therapies for CKD Comorbid Depression Trial (CONCORD) is a multicenter, randomized, placebo-controlled trial to evaluate 2 distinct treatment strategies compared with 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-sustained release 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 effects on patient-reported outcomes (PROs) will also be explored.

A total of 202 patients were randomized across 3 US sites. Mean (SD) age was 56 (12) years and mean estimated glomerular filtration rate 24.6 (10.9) ml/min per 1.73 m²; 42% were men, 29.7% were African American, and 29.4% were Hispanic persons. The percentages with CKD G3b, G4, G5, and G5D were 35.6%, 43.6%, 10.9%, and 9.9%, respectively.

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.