Efficacy and Safety of SP16 in Preventing Acute Kidney Injury in At-risk Subjects With Chronic Kidney Disease Undergoing Elective Cardiac Surgery Using the Heart-lung-machine (EASE-AKI)

Efficacy and Safety of SP16 in Preventing Acute Kidney Injury in At-risk Subjects With Chronic Kidney Disease Undergoing Elective Cardiac Surgery Using the Heart-lung-machine: A Prospective, Randomized, Double-blind, Placebo-controlled Clinical Trial (EASE-AKI)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: AKI - Acute Kidney Injury
• Intervention / Treatment: Drug: SP16-3M; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mario Schiffer; Phone Number: +4991318539002; Email: med4@uk-erlangen.de
• Study Contact Backup: Name: Tilman Jobst-Schwan; Email: med4@uk-erlangen.de

Study Locations

• Germany
  • Bavaria
    • Erlangen, Bavaria, Germany, 91054
      • Universitätsklinikum Erlangen
      • Contact: Mario Schiffer; Phone Number: +4991318539002; Email: med4@uk-erlangen.de
      • Contact: Tilman Jobst-Schwan; Email: med4@uk-erlangen.de
      • Principal Investigator: Mario Schiffer

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.
• Written informed consent obtained from the participant.
• Understanding of study procedures and willingness to abide by all procedures during the course of the clinical trial.
• CKD Stage 2-3b with eGFR ≤90 and ≥30 ml/min/1.73 m2 (according to 2021 CKD-EPI equation) known for ≥ 3 months prior to enrollment
• BMI ≥19 kg/m² to ≤40 kg/m².
• Contraceptive measures:

Female participants must fulfil at least one of the following criteria of highly effective contraception (according to CTFG recommendations v1.2) during and up to 3 months after the end of study participation:

• Menopause (at least 12 months of natural amenorrhoea or 6 months of amenorrhoea with serum FSH >40 mU/ml) OR
• Condition after bilateral ovariectomy or hysterectomy for at least 6 weeks prior to the screening appointment (Visit 1a, Day 54 to -2) OR

• Regular, correct and reliable use of a contraceptive method with an error rate ≤1% per year:

  1. Inhibition of ovulation by estrogen and progesterone combination preparations (oral, intravaginal, or transdermal) or
  2. Inhibition of ovulation by progesterone monopreparations (oral, per injectionem [depot injections], or implant) or
  3. Intrauterine device, hormone coil OR
• Bilateral tubal ligation OR
• Vasectomy of all partners OR
• Sexual abstinence.

Male participants must fulfill at least one of the following contraceptive criteria during and up to 3 months after the end of participation in the study:

• Vasectomy OR
• Regular, correct, and reliable use of condoms

Exclusion Criteria:

• 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).
• Known diagnosis of dementia or other clinical signs of mental illness that will prevent full understanding.
• Known diagnosis of severe COPD (Gold 3) and/or FEV1 < 1 l/s.
• Heart failure with severity of symptoms according to NYHA IV.
• Heart failure with impaired cardiac pump function (LVEF <35%).
• Acute onset or ongoing sepsis - sepsis is defined as the presence of a confirmed or putative infection, along with a dysregulated systemic immune reaction leading to organ dysfunction.
• Clinical signs of a currently active infection including endocarditis requiring antibiotic treatment.
• Clinical signs of an acute viral infection.
• Serious underlying disease(s) or very poor general medical condition, so that in the investigator's judgment the person is not expected to survive ICU or hospital stay.
• Patient who has an active (requiring treatment) malignancy or history within 5 years prior to enrollment in the study, of solid, metastatic or hematologic malignancy with the exception of basal or squamous cell carcinoma of the skin that has been removed.
• Administration of iodinated contrast agent within 24 hours prior to cardiac surgery
• Recent (discontinued in the last 14 days before V1a or V1b) or current treatment with immunosuppressive drugs, including, but not limited to, high dose corticosteroids [> 1 mg/kg of prednisone equivalent], tumour necrosis factor alpha blockers, or ciclosporin.
• Current regular use of anti inflammatory drugs such as NSAID, with discontinuation not possible. (however, if these medications are discontinued in the last 10 days before V2, the participant is eligible to participate). ASA up to 100 mg per day is allowed.
• Systemic corticosteroid therapy (any dose).
• Known active chronic inflammatory disease (including, but not limited to, rheumatoid arthritis or systemic lupus erythematosus).
• Known allergy to SP16 or to other ingredients of the IMP.
• Person who is not willing to use highly effective contraceptive measures (according to CTFG recommendations v1.2).
• Pregnant women.
• Breastfeeding women.
• Current participation in another interventional clinical study (register studies or non-interventional, observational studies excluded).
• Employee or direct relative of an employee of the study site, the CRO, or the Sponsor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; In 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.
Active Comparator: SP16-3M	Drug: SP16-3M; The 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Within 72 hours after index surgery
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	Within 7 days after index surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From the timepount of index surgery to the end of surveillance 90±7 days after index surgery
Necessity of renal replacement therapy (RRT)	The frequency of RRT post-surgery will be recorded.	From the timepoint of index surgery to the end of surveillance 90±7 days after index surgery
Duration of renal replacement therapy (RRT)	Duration of RRT measured by starting date [yyyy-mmm-dd] and end date [yyyy-mmm-dd]	From the timepoint of index surgery to the end of surveillance 90±7 days after index surgery
Cardiac function on Day 90±7 days after cardiac index surgery	Cardiac function on Day 90±7 days after cardiac index surgery compared to pre surgical assessment (Visit 1) assessed by transthoracic echocardiography (TTE).	At the end of surveillance 90±7 days after index surgery
Cardiac function on Day 0 post-surgery (Visit 3), Day 1, and on Day 5 after index surgery	Cardiac function on Day 0 post-surgery (Visit 3), Day 1, and on Day 5 after index surgery assessed by point of care echocardiography (TTE) compared to pre-surgical assessment (Visit 1).	Within 5 days after index surgery
Concentration of NT-proBNP (serum)	NT-proBNP serum concentration on Day 1, Day 7, and Day 90±7 after index surgery compared to pre-surgical assessment on Day 0 (Baseline; Visit 2).	From enrollment to the end of surveillance 90±7 days after index surgery
Central venous oxygen saturation (ScvO2) (blood gas analysis)	Central venous oxygen saturation (ScvO2) on Day 1, Day 5 and Day 7 after index surgery compared to pre-surgical assessment on Day 0 (Baseline; Visit 2).	Within 7 days after surgery
Frequency of all-cause death	Frequency of all-cause death within 90±7 days (3 months) after cardiac index surgery.	From the timepopint of index surgery to the end of surveillance 90±7 days after index surgery
Frequency of sustained impaired renal function	Frequency of sustained impaired renal function defined as ≥25% increase in Serum Creatinine at Day 90±7 compared to baseline.	From the timepopint of index surgery to the end of surveillance 90±7 days after index surgery
Frequency of sustained impaired renal function requiring at least one dialysis	Frequency of sustained impaired renal function requiring at least one dialysis during the post-surgical interval until Day 90±7 (end of observation period).	From enrollment to the end of surveillance 90±7 days after index surgery.
Frequency of AE and SAE within 7 days after cardiac index surgery.	The incidence of adverse events (AEs) and severe adverse events (SAEs) will be assessed in detail in addition to the primary outcome measure within 7 days after cardiac index surgery.	Within 7 days after index surgery
Frequency of AE and SAE during the observation period.	Frequency of AE and SAE during the entire observation period.	From enrollment to the end of surveillance after 90±7 days after index surgery.
Number of participants with at least one SAE	Number of participants with at least one SAE during the observation period.	From the first timepoint of SP16 administration to the end of surveillance 90±7 days 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	Within 7 days after index surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time [hours] of the Intensive Care Unit (ICU) stay.		From enrollment to the end of surveillance after 90±7 days after index surgery.
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).	Before and within 7 days after index surgery
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).	Before and within 7 days after index surgery
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).	Before and within 7 days after index surgery
Concentration of IL-10 (serum)	IL-10 concentration (pg/ml) at defined post-surgical time points within 7 days after index surgery compared to pre-surgical assessment at baseline (Visit 2).	Before and within 7 days after index surgery
Concentration of TIMP2 (urine)	TIMP2 concentration (pg/ml) at defined post-surgical time points within 7 days after index surgery compared to pre-surgical assessment at baseline (Visit 2).	Before and within 7 days after index surgery
Concentration of IGFBP7 (urine)	IGFBP7 concentration (pg/ml) at defined post-surgical time points within 7 days after index surgery compared to pre-surgical assessment at baseline (Visit 2).	Before and within 7 days after index surgery

Collaborators and Investigators

• Sponsor: University of Erlangen-Nürnberg Medical School
• Collaborators: Serpin Pharma, LLC

Publications and helpful links

Helpful Links

• Approved study protocol by the European Medicines Agency (EMA)

Study record dates

Study Major Dates

• Study Start (Estimated): June 18, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: May 21, 2026
• First Submitted That Met QC Criteria: June 16, 2026
• First Posted (Actual): June 22, 2026

Study Record Updates

• Last Update Posted (Actual): June 25, 2026
• Last Update Submitted That Met QC Criteria: June 22, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: cardiac surgery; CKD; AKI
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Renal Insufficiency; Acute Kidney Injury
• Other Study ID Numbers: 0740; 2025-522491-89-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No