Table 2

Other secondary endpoints and exploratory endpoints

Other secondary endpoints
  • Postbaseline changes in renal function

    • SCr and cystatin C (and corresponding eGFR values) at 12, 24,48 and 72 hours, respectively, and at day 7/discharge, day 30 and day 90.

    • Change from baseline, up to day 7/discharge, of peak SCr and cystatin C.

  • Time-corrected AUC of cystatin C for day 1 to day 4 (72 hours after first dose of IMP).

  • Need for renal replacement therapy

    • Dialysis treatment (for any reason) within 72 hours and within 7 days after end of surgery.

    • Dialysis free days from end of surgery to day 30 and day 90, respectively.

  • MAKE at day 30 and day 90, defined as death, any dialysis or ≥25% reduction of eGFR compared with baseline chronic kidney disease epidemiology collaboration equation (either SCr, cystatin C or both).22–24

  • AKI characteristics

    • AKI within 72 hours after first dose of IMP based on cystatin C and/or UO (AKI of any stage/severity defined as cystatin C ≥1.5 baseline, OR UO <0.5 mL/kg/hour for ≥6 hours).

    • AKI within 7 days after first dose of IMP (based on SCr and/or UO criteria, or cystatin C and/or UO criteria).

    • AKI persistence, defined as an AKI (KDIGO definition) developing within 72 hours after first dose of IMP and with a duration of ≥72 hours. persistence will also be assessed per AKI severity stage*.

    • AKI severity stage* within 72 hours and within 7 days after first dose of IMP

      • *Severity of AKI defined as the following:

        • Stage 1: SCr 1.5–1.9 times baseline within 7 days, or ≥0.3 mg/dL (≥26.5 µmol/L), or urine output <0.5 mL/kg/hour for 6 to <12 hours.

        • Stage 2: SCr 2.0–2.9 times baseline within 7 days or urine output <0.5 mL/kg/hour for ≥12 hours.

        • Stage 3: SCr 3.0 times baseline within 7 days, or increase in SCr 4.0 mg/dL (≥353.6 µmol/L), or initiation of renal replacement therapy or urine output <0.3 mL/kg/hour for ≥24 hours or anuria for ≥12 hours.

Exploratory Endpoints
  • Postbaseline changes in urine albumin to creatinine ratio and urine protein to creatinine ratio at day 4, day 30 and day 90.

  • Pharmacokinetics of RMC-035 in plasma (AUC and Cmax).

  • Presence and titers of ADA at day 1 (presurgery), day 30 and day 90.

  • Characteristics of ADA developed at day 30 and day 90 with regards to isotype, neutralising capacity and cross-reactivity with endogenous alpha-1-microglobulin (A1M).

Postbaseline changes in kidney and cardiac biomarkers
  • Kidney biomarkers: urine kidney injury molecule 1, neutrophil gelatinase-associated lipocalin, tissue inhibitor of metalloproteinase 2, insulin like growth binding factor protein 7, chemokine ligand 14 (CCL-14), interleukin-18 (IL-18), liver fatty acid binding protein and 8-hydroxy-2'- deoxyguanosine.

  • Cardiac biomarkers: plasma N-terminal-prohormone of brain natriuretic peptide and cardiac troponin I and T (cTnI, cTnT).


Hospitalisation time and discharge facility
  • Length of index ICU stay and index hospital stay.

    • Index ICU stay (in days) defined as the duration of stay in the ICU.

    • Immediately following surgery or recovery room postsurgery until ICU discharge.

    • Index hospital stay (in days) is defined as the duration of stay in the hospital from the day of surgery to hospital discharge for the index surgery.

  • Nature of subject discharge facility (eg, home, skilled nursing facility, rehabilitation centre).


Health-related quality of life assessments
  • Change from baseline to day 90 in the following patient-reported outcomes:

    • MOS 36-Item Short Form Survey Instrument.

    • European Quality of Life 5 Domain 5-Level Score.

  • ADA, antidrug antibody; AKI, acute kidney injury; AUC, area under the curve; eGFR, estimated glomerular filtration rate; ICU, intensive care unit; IMP, investigational medicinal product; MAKE, major adverse kidney events; MOS, Medical Outcome Study; UO, urine output.