Incremental Hemodialysis for Veterans in the First Year of Dialysis (IncHVets): A Pragmatic, Multi-Center, Randomized Controlled Trial

Veterans Health Administration, Decatur PA

Investigators

Abstract

PROJECT SUMMARY Each year approximately 12,000 Veterans develop end-stage renal disease (ESRD) and initiate dialysis treatment. These patients comprise >10% of the US incident ESRD population. Dialysis is costly and associated with impaired health-related quality of life (HRQOL) and high mortality risk, particularly in the first dialysis year. The current paradigm is to start treatment with full-dose thrice-weekly hemodialysis (HD) irrespective of patients' residual kidney function (RKF), and this abrupt transition increases patients' and care- partners' burden and suffering and may limit their preferences. Furthermore, recent evidence suggests that Veterans who receive dialysis in a VA center have greater survival compared to those treated in non-VA units. Although not currently the standard of care, evidence suggests that a gradual or incremental dialysis transition using an initial twice-weekly HD schedule may confer substantial benefits including more dialysis- free time, longer RKF preservation, vascular access longevity, less intradialytic hypotension and end-organ damage, reduced post-dialysis fatigue, and less patient suffering. Hence, an incremental dialysis transition may result in improved HRQOL through improved physical function, less fatigue, greater energy, and improved patient satisfaction and life participation by mitigating the burden of excessive dialysis in daily life. Pragmatic studies with immediate clinical impact are urgently needed to shift the focus of dialysis from an abrupt thrice-weekly HD start to a safe and effective personalized dialysis regimen. Moreover, implementing a twice-weekly HD schedule would allow 20% more Veterans to receive care within a VA-based dialysis unit. In the spirit of RFA CX-21-006 for clinical trials, in this multiple-PI, multi-site, pragmatic, 1:1 randomized controlled trial (RCT), parallel with Veterans' routine dialysis therapy, we will test the safety and efficacy of an incremental twice-weekly HD protocol, compared to standard-of-care thrice-weekly HD, in Veterans who meet predefined eligibility criteria. We plan to compare twice-weekly (incremental) with thrice-weekly (conventional) HD initiation in 252 Veterans with incident ESRD, who will transition to maintenance HD therapy in six VA centers. Using quarterly assessments for up to 12 months, we will examine the Short Form 36 (SF36) HRQOL physical component score as the primary outcome, as well as Dialysis Symptom Index and SF36 energy/ fatigue score as secondary endpoints. Additional secondary outcomes will include preservation of RKF, dialysis adequacy, nutritional status, and protein-energy wasting markers to be measured quarterly. Safety assessments will include mortality, dialysis withdrawals, emergency room visits, hospitalizations, hyperkalemia, and major adverse cardiovascular events. In a substudy examining exploratory outcomes in 112 Veterans from three VA centers in the parent trial, we will also examine of cardiac measures including left ventricular mass, as well as nutritional/physical function indices of muscle mass and physical performance. Our proposed pragmatic RCT addresses a major unmet need in Veterans with incident ESRD initiating dialysis by focusing on improving HRQOL and preserving RKF, the two strongest predictors of survival and patient satisfaction. The results of this study may enable more Veterans to receive therapy in a VA based dialysis center. Our study may lead to a paradigm shift with immediate impact on kidney care in Veterans and in the broader ESRD population. The pragmatic design will permit a rapid scaling-up of the interventions in larger settings since the RCT takes advantage of resources and personnel that are readily available in VA centers under experienced investigators and clinicians across multiple VA sites nationwide. This proposed study challenges the current standard of care of outright thrice weekly HD in the first year of dialysis therapy, during which patients' suffering and mortality are the highest, and is less likely to be supported by for-profit dialysis providers given the perceived reduction in revenue if twice-weekly HD is to be implemented broadly.