Patient-reported outcomes in a pilot clinical trial of twice-weekly hemodialysis start with adjuvant pharmacotherapy and transition to thrice-weekly hemodialysis vs conventional hemodialysis

BACKGROUND: Physical and emotional symptoms are prevalent in patients with kidney-dysfunction requiring dialysis (KDRD) and the rigors of thrice-weekly hemodialysis (HD) may contribute to deteriorated health-related quality of life. Less intensive HD schedules might be associated with lower symptom and/or emotional burden. METHODS: The TWOPLUS Pilot study was an individually-randomized trial conducted at 14 dialysis units, with the primary goal to assess feasibility and safety. Patients with incident KDRD and residual kidney function were assigned to incremental HD start (twice-weekly HD for 6 weeks followed by thrice-weekly HD) vs conventional HD (thrice-weekly HD). In exploratory analyses, we compared the two treatment groups with respect to three patient-reported outcomes measures. We analyzed the change from baseline in the score on Dialysis Symptom Index (DSI, range 0–150), Generalized Anxiety Disorder-7 (GAD-7, range 0–21), and Patient Health Questionnaire-9 (PHQ-9, range 0–27) at 6 (n = 20 in each treatment group) and 12 weeks (n = 21); with lower scores denoting lower symptom burden. Analyses were adjusted for age, race, gender, baseline urine volume, diabetes mellitus, and malignancy. Participants’ views on the intervention were sought using a Patient Feedback Questionnaire (n = 14 in incremental and n = 15 in conventional group). RESULTS: The change from baseline to week 6 in estimated mean score (standard error; P value) in the incremental and conventional group was − 9.7 (4.8; P = 0.05) and − 13.8 (5.0; P = 0.009) for DSI; − 1.9 (1.0; P = 0.07) and − 1.5 (1.4; P = 0.31) for GAD-7; and − 2.5 (1.1; P = 0.03) and − 3.5 (1.5; P = 0.02) for PHQ-9, respectively. Corresponding changes from week 6 to week 12 were − 3.1 (3.2; P = 0.34) and − 2.4 (5.5; P = 0.67) in DSI score; 0.5 (0.6; P = 0.46) and 0.1 (0.6; P = 0.87) in GAD-7 score; and − 0.3 (0.6; P = 0.70) and − 0.5 (0.6; P = 0.47) in PHQ-9 score, respectively. Majority of respondents felt their healthcare was not jeopardized and expressed their motivation for study participation was to help advance the care of patients with KDRD. CONCLUSIONS: This study suggests a possible mitigating effect of twice-weekly HD start on symptoms of anxiety and depression at transition from pre-dialysis to KDRD. Larger clinical trials are required to rigorously test clinically-matched incrementally-prescribed HD across diverse organizations and patient populations. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study identifier NCT03740048, registration date 14/11/2018. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12882-022-02946-w.