EMBEDDING RESEARCH ON INCREMENTAL HEMODIALYSIS ON INCREMENTAL HEMODIALYSIS INTO ROUTINE CARE: PATIENT MONITORING FRAMEWORK FROM THE TWO PLUS TRIAL. TwoPlus Trial

Pragmatic randomized controlled trials (RCTs) must operate within routine clinical workflows while ensuring patient safety. Incremental hemodialysis (HD)—initiating treatment twice weekly in patients with residual kidney function (RKF) and escalating frequency as indicated—differs fundamentally from a conventional thrice-weekly start. The multicenter TwoPlus Trial compares incremental to conventional HD initiation in a pragmatic setting. We report the patient monitoring framework developed to safeguard safety, feasibility, and fidelity in this trial.

The TwoPlus trial is enrolling 350 adults initiating chronic IHD with RKF (kidney urea clearance ≥2.0 mL/min and urine output ≥500 mL/24h), randomized 1:1 to incremental or conventional IHD initiation. The primary outcome is a composite of all-cause death, hospitalization, or emergency department visits; secondary outcomes include RKF preservation and adherence. Participant monitoring is framed along five complementary layers: (a) provider engagement, including eligibility confirmation and ongoing communication with treating nephrologists, (b) regular patient check-ins by the research team, (c) team-based review of longitudinal clinical data from dialysis EMRs, (d) digital surveillance through dialysis and healthcare system EMRs supplemented by regular data summary reports, and (e) site-level adaptation of patient monitoring (Figure 1a). Trial pragmatism was assessed using the PRECIS-2 tool, which rates nine design domains—eligibility, recruitment, setting, organization, intervention delivery, flexibility-adherence, follow-up, primary outcome, and analysis—on a 1-to-5 scale, with higher scores indicating greater alignment with pragmatic trial design.

Implementation of incremental HD across academic and community sites is feasible. Provider engagement proved critical for maintaining protocol fidelity, including delivery of the allocated treatment assignment at randomization. Structured training and ongoing communication mitigated limited prior familiarity with incremental HD at sites where this approach was not routine. Human touchpoints, including monthly check-ins, supplemented by dialysis staff input, identified clinical concerns not consistently documented in EMRs. Team-based reviews between research teams and treating providers—integrating dialysis EMR data, residual kidney function measures, and patient-level data electronic reports—facilitated timely treatment adjustments. Integration of healthcare system EMR with automated alerts of adverse events captured hospitalizations and other clinical events in near real time. Site-level adaptations allowed patient monitoring responsibilities to be tailored across diverse operational infrastructures, ranging from provider-led to research team–led or shared models, and included integration across both academic and private practices, as well as academic or privately-owned dialysis networks. PRECIS-2 scoring confirmed that the trial is pragmatic in domains of setting (mean [SD], 4.00 [1.12]), intervention delivery (4.13 [0.33]), primary outcome ascertainment (4.63 [0.48]), and analytic approach (4.50 [0.71]) (Figure 1b).

The TwoPlus trial layered monitoring framework combines human oversight, provider engagement, and digital infrastructure to enable safe, pragmatic testing of incremental HD. Early experience demonstrates feasibility across diverse dialysis settings. This model may inform the design of monitoring strategies for future pragmatic nephrology trials evaluating emerging interventions.