This clinical study investigates the safety and potential effectiveness of the investigational drug SP16 in preventing acute kidney injury in patients with pre-existing chronic kidney disease who are undergoing cardiac surgery involving the use of cardiopulmonary bypass (heart-lung machine).
SP16 is an investigational medicinal product that has not yet been approved for clinical use. To date, it has been studied in 28 individuals. The sponsor aims to evaluate whether SP16 can safely reduce or prevent kidney damage associated with the inflammatory and ischemia-reperfusion processes that may occur during cardiac surgery with cardiopulmonary bypass.
Participation in the study extends over a period of slightly more than five months. Screening procedures are performed within approximately seven weeks to two days before the scheduled surgery to determine eligibility for participation. During the hospitalization for cardiac surgery, which is expected to last approximately 10 days, a total of 11 study visits are conducted. Follow-up assessments include a telephone contact approximately one month after hospital discharge and a final on-site study visit approximately three months after discharge.
This is a randomized, double-blind, placebo-controlled clinical trial. Participants are randomly assigned to receive either SP16 or a placebo, which contains no active ingredient. Neither the participants nor the investigators know which treatment has been assigned during the study period.
Based on previous preclinical and early clinical findings, SP16 may have the potential to reduce or mitigate kidney injury caused by the use of the heart-lung machine during cardiac surgery. However, since the efficacy of SP16 has not yet been proven, no clinical benefit can be guaranteed. Participants receiving placebo are not expected to derive a direct therapeutic benefit from study treatment.
Individual aged ≥18 years.
Male or female.
Scheduled for CABG OR aortic valve surgery (aortic valve replacement or repair alone, with or without aortic root repair) OR mitral valve surgery OR aortic/mitral valve surgery combined with CABG.
Use of the CPB during surgical intervention expected.
CKD stages 4-5 with eGFR <30 ml/min/1.73 m2 pre-surgery as determined by CKD EPI.
Previous cardiac surgery.
Person has a kidney transplant or another solid organ transplant.
Person is scheduled for intermittent or continuous renal replacement therapy (dialysis).
Parallel
SP16-3M
DrugThe IMP is injected subcutaneously at two different time points. The first administration will take place pre-surgically, in the area of the operating theatre, when the participant is under anesthesia. The second administration will be performed post-surgically, 9±1 h after the first administration. At each of the two injection timepoints, a fixed dose of 6 mg SP16-3M is administered by two s.c. injections of 2 ml (concentration 1.5 mg/ml) each at two different injection sites.
Placebo
DrugIn the placebo group, placebo (dextrose 5%) is injected subcutaneously at the same timepoints as the IMP, each time slowly (over about 30 seconds) at a fixed volume of 2 ml each at two different injection sites.
Frequency of adverse events (AEs) and severe adverse events (SAEs)
Frequency of adverse events (AEs) and severe adverse events (SAEs) will be assessed within 72 hours after index surgery and SP16 administration.
Frequency of Cardiac Surgery Associated Acute Kidney Injury (CSA-AKI)
Number of participants who develop CSA-AKI during hospital stay defined by Kidney Disease: Improving Global Outcomes \[organization\] (KDIGO) stage 1 or higher. If at least one of the following criteria is observed in the interval since end of index surgery and the 7-day assessment, a participant will be considered to have developed CSA-AKI: * Increase in Serum Creatinine (SCr) by ≥0.3 mg/dl (\>26.5 μmol/l) within 168±4 hours after index surgery (defined as the period since cardiopulmonary bypass \[CPB\] was terminated and systemic circulation resumed). * Increase in SCr to ≥1.5 times the baseline value, using the highest SCr value within 168±4 hours after index surgery. * Decrease in urine output \<0.5 ml/kg/h for more than 6 hours within 168±4 h after index surgery
Severity of post-surgical CSA-AKI
Highest CSA-AKI stage value according to the stage classification of the KDIGO-AKI (https://kdigo.org) based on serum creatinine level (mg/dl) and urinary output (ml/kg/hour) in the 7-day period after the index surgery: Stage 1: serum creatinine level 1.5 to 1.9 times baseline within 7 d OR ≥ 0.3 mg/dl (≥ 26.5 μmol/l) increase within 48 h; urine output \< 0.5 ml/kg/h for 6 h Stage 2: serum creatinine level 2.0 - 2.9 times baseline within 7 d; urine output \< 0.5 ml/kg/h for ≥ 12 h Stage 3: serum creatinine level 3.0 times baseline OR increase to ≥ 4.0 mg/dl OR Initiation of renal replacement therapy within 7 d; urine output \< 0.3 ml/kg/h for ≥ 24 h OR anuria for ≥ 12 h
Duration of post-surgical CSA-AKI
Number of days after post-surgical onset of CSA-AKI until re-achievement of baseline level of serum creatinine (defined as a return of creatinine to \<0.3 mg/dl above baseline value) or discharge from hospital, whichever comes first.
Necessity of renal replacement therapy (RRT)
The frequency of RRT post-surgery will be recorded.
Duration of renal replacement therapy (RRT)
Duration of RRT measured by starting date \[yyyy-mmm-dd\] and end date \[yyyy-mmm-dd\]
Time [hours] of the Intensive Care Unit (ICU) stay.
Concentration of Cystatine C (serum)
Cystatine C concentration (mg/l) at defined post-surgical time points within 7 days after index surgery compared to pre-surgical assessment at baseline (Visit 2).
Concentration of NGAL (urine)
urine-NGAL concentration (ng/ml) at defined post-surgical time points within 7 days after index surgery compared to pre-surgical assessment at baseline (Visit 2).
Concentration of IL-6 (serum)
IL-6 concentration (pg/ml) at defined post-surgical time points within 7 days after index surgery compared to pre-surgical assessment at baseline (Visit 2).
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University of Erlangen-Nürnberg Medical School
Lead sponsor
Serpin Pharma, LLC
Collaborator
