R2R01 for Cardiac surgery-associated acute kidney injury (CSA-AKI) | Acute kidney injury

Inclusion criteria

• {"criterion_text":"- Patient is able to communicate well with the Investigator, understands and is willing to comply with all requirements of the study, and understands and signs the written informed consent form (ICF)\n- At least 18 years of age\n- Subject is scheduled for non-emergent CABG (single or multiple vessels), valve surgery (single or multiple valves), surgery of the ascending part of the aorta, or a combination of the above, involving cardiopulmonary bypass (CPB), AND risk factors for acute kidney injury (AKI) are present (at screening) as specified below: a. If only one type of surgery is scheduled, at least two AKI risk factors should be present b. If any combined surgery is scheduled, at least one AKI risk factor should be present. Risk factors for AKI: •\tDiabetes mellitus on pharmacological treatment •\tConfirmed diagnosis of hypertension •\tDocumented history of Chronic Heart Failure with New York Heart Association (NYHA) class III or higher (see section 11.5 in Appendix) •\tLeft ventricular ejection fraction (LVEF) ≤40% •\tPeripheral vascular disease defined as one or more of the following: claudication, carotid occlusion or >50% stenosis, amputation for arterial disease, previous or planned intervention on the abdominal aorta, limb arteries or carotids •\tStroke/transient ischemic attack (TIA) defined as sudden onset of focal or global brain, spinal cord, or retinal vascular damage, resulting in symptoms and signs of acute nervous system defects, associated with cerebral circulation disorders •\tDocumented atrial fibrillation (AF) on the ECG performed at the screening visit •\tAnemia with hemoglobin ≤11 g/dL at any time during the 3-month period before or at the time of screening •\tBody Mass Index (BMI) ≥ 30 kg/m2 •\tAge ≥70 years at the time of screening\n- Have stable renal function per Investigator assessment\n- Subject agrees not to participate in another interventional study after signing the ICF and until the end of study (EoS) visit has been completed"}

Exclusion criteria

• {"criterion_text":"- Patient currently enrolled into another interventional clinical trial\n- Patient with a kidney transplant\n- Subject has a known or suspected glomerulonephritis at the time of randomization\n- Cardiogenic shock, hemodynamic instability, mechanical ventilation, intra-aortic balloon pump (IABP), left ventricular assist device (LVAD) or other forms of mechanical circulatory support (MCS), within 7 days prior to surgery\n- Patient received inotropes or vasopressors within 48 hours prior to the day of surgery\n- Known or suspected sepsis\n- Confirmed or suspected endocarditis\n- Other current active infection requiring antibiotic treatment\n- Patient has severe liver disease (Child-Pugh score >7 points)\n- Recently received (within the last 4 weeks) or is anticipated to receive before the end of the study chemotherapy which can interfere with kidney function (e.g. Platinum agents)\n- Patient previously enrolled and randomized into this study\n- Subject is scheduled for emergent surgery\n- Pregnant or nursing (lactating) women, where pregnancy was defined as the state of a female after conception and until the termination of gestate, confirmed by a positive human chorionic gonadotropin laboratory\n- Known hypersensitivity to the study drug or any of its excipients\n- Any medical or social condition deemed by the investigator to be likely to interfere with a patient’s ability to give informed consent, cooperate, and participate in the study or to be likely to interfere with the interpretation of the results\n- Cardiac surgery planned to be performed \"off-pump\" without CPB\n- Expected CPB duration < 60 minutes\n- Body weight <50 kg; >120 kg\n- Presence of AKI (KDIGO criteria) at the time of randomization\n- Current, recent (within 4 weeks), or scheduled renal replacement therapy\n- Patients who are post-nephrectomy\n- Patients with CKD of equal or more than stage IV (GFR≤30 ml/min/1.73 m2)"}

Primary endpoints

• {"endpoint_text":"- Proportion of subjects developing AKI within 7 days after start of on-pump cardiac surgery based on SCr (AKI of any stage according to KDIGO criteria, see above)","definition_or_measurement_approach":"AKI determined within 7 days after start of on-pump cardiac surgery based on serum creatinine (SCr) using KDIGO criteria"}
• {"endpoint_text":"- Nature, frequency and severity of treatment-emergent adverse events (TEAEs).","definition_or_measurement_approach":"Safety assessed by recording nature, frequency and severity of TEAEs (treatment-emergent adverse events)"}

Secondary endpoints

• {"endpoint_text":"- Severity grade of AKI within 7 days after start of cardiac surgery based on SCr (according to KDIGO criteria, see above).","definition_or_measurement_approach":"AKI severity graded using KDIGO criteria within 7 days post-surgery"}
• {"endpoint_text":"- Duration of AKI defined as the number of days meeting the definition of AKI (according to KDIGO criteria, see above).","definition_or_measurement_approach":"Duration measured as number of days meeting KDIGO AKI definition"}
• {"endpoint_text":"- Change in SCr and cystatin C (and corresponding eGFR values) at postoperative hours 12, 24, 48, 72, and postoperative Days 7 and 30, versus baseline","definition_or_measurement_approach":"Laboratory measurements of serum creatinine and cystatin C and derived eGFR at specified postoperative timepoints versus baseline"}
• {"endpoint_text":"- Proportion of subjects with a major adverse kidney event (MAKE) defined as all-cause mortality, RRT and/or ≥ 25% sustained reduction of kidney function (i.e., a reduction of eGFR of 25% or more compared to the baseline pre-surgery sample, using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equations (with either SCr, CyC, or both) at postoperative Day 7 and at postoperative Day 30","definition_or_measurement_approach":"MAKE defined as all-cause mortality, renal replacement therapy (RRT) and/or ≥25% sustained reduction in eGFR from baseline (CKD-EPI) assessed at Day 7 and Day 30"}
• {"endpoint_text":"- Length of ICU stay (in hours) defined as the duration of stay in the ICU immediately following surgery (or recovery room post-surgery) until ICU discharge","definition_or_measurement_approach":"Measured duration in hours from immediate post-surgery ICU/recovery room admission until ICU discharge"}
• {"endpoint_text":"- Length of Hospital stay (in days) defined as the duration of stay in the hospital from the day of surgery to hospital discharge","definition_or_measurement_approach":"Measured duration in days from day of surgery to hospital discharge"}
• {"endpoint_text":"- ICU free days and hospital free days","definition_or_measurement_approach":"Calculated ICU-free days and hospital-free days (methodology as per protocol)"}
• {"endpoint_text":"- Proportion of subjects readmitted to the hospital at postoperative Day 30","definition_or_measurement_approach":"Proportion of subjects with hospital readmission within 30 days postoperatively"}

Germany

Earliest CTIS Part Ii Submission Date

19-11-2025

Latest Decision Or Authorization Date

06-03-2026

Processing Time Days

107

Number Of Sites

6

Number Of Participants

50

Italy

Earliest CTIS Part Ii Submission Date

18-02-2026

Latest Decision Or Authorization Date

04-03-2026

Processing Time Days

14

Number Of Sites

15

Number Of Participants

390

Primary sponsor

Full Name

River 2 Renal Corp.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Third parties

• {"country":"Italy","full_name":"Advice Pharma Group S.r.l.","duties_or_roles":"Pharmacovigilance activities; Vendors management (including laboratories for centralized analyses and pharmaceutical manufacturing units for IMP management); Preparation and drafting of the Clinical Study Report (CSR); Management of the electronic Trial Master File (eTMF); Contract negotiation with investigative sites on behalf of the Sponsor; Site selection activities","organisation_type":"Pharmaceutical company"}