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

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.

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.