RESOLVE-D, the Randomised Evaluation of SOdium dialysate Levels on Vascular Events Trial-Deutschland

• Applicant: Dr. Jule Pinter
• Subject Area: Nephrology ; Epidemiology and Medical Biometry/Statistics ; Public Health, Healthcare Research, Social and Occupational Medicine
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 449742175

Background and objectives: The number of chronic haemodialysis (HD) patients is expected to double worldwide by 2030 as the incidence of chronic renal failure increases. Sudden cardiac death leads to death in a quarter of cases. This is preceded by left ventricular hypertrophy and arterial vascular stiffness, associated with sodium retention and chronic fluid overload. Associations between sodium and patient survival are heterogeneous, and, the prescription of dialysate sodium varies depending on local practice with no definitive evidence for better outcomes. While some recommend routinely lowering dialysate sodium, others counter that standard practice should be maintained. The global RESOLVE (Randomized Evaluation of dialysate SOdium on Vascular Events) study, global collaboration under Australian leadership, will clarify whether a default dialysate sodium concentration of 137 mmol/l compared to 140 mmol/l will lead to fewer cardiovascular events and deaths in adult HD patients. The German participation is led by the Division of Nephrology at Würzburg University Hospital. We will implement a German sub-study, investigating whether less sodium exposure during dialysis reduces fluid overload as measured by bioimpedance spectroscopy, an important mechanistic sub-study.Study design: RESOLVE is a pragmatic, cluster-randomized, open-label trial to evaluate the comparative effectiveness of two commonly used dialysate sodium concentrations in real world conditions. 414 hemodialysis centers will be enrolled in the global study, one third of which have already been randomized in four other countries. We will contribute 15 HD centers with 2550 adult patients. In six experienced centers with 400 HD patients the German bioimpedance sub-study will be implemented. Intervention: Cluster randomization of an entire dialysis center to a one of two default dialysate sodium concentration, 137 and 140 mmol/l. German sub-study intervention: Bioimpedance spectroscopy measurements in both study arms at randomization and annually during follow-up. Global primary endpoint: safety and efficacy endpoint, defined as composite of acute myocardial infarction, stroke, and death from any cause. Primary endpoint of the German sub-study: fluid overload (defined as the difference between total body water and expected individual total body water). Secondary endpoints: Composite of primary endpoint and hospitalization for heart failure and individual components of the composites.Randomization: stratifiziert by region und center size. The intention-to-treat analysis will use a time-to-event outcome for clusters. The trial is endpoint-driven and we estimated that 26910 primary outcome events would be needed to detect a 10% lower relative risk, with 90% power using a two-sided alpha level of 5% and assuming an annual control event rate for the primary outcome of 15%. The trial duration is endpoint driven, and will run until the required number of events have accrued globally.

• DFG Programme: Clinical Trials
• Co-Investigators: Professor Dr. Peter U. Heuschmann; Professorin Dr. Elke Schäffner; Privatdozent Dr. Christoph Wanner