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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsklinikum Erlangen AöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Not possible to specify, Diseases [C] - Cardiovascular Diseases [C14]

Decision date (initial)

2026-02-02

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the safety of SP16 administration and its ability to prevent CSA-AKI as defined by KDIGO criteria, in participants with CKD 2-3b undergoing planned cardiac surgery.

Secondary objectives 1

1. To evaluate the effect of SP16 on • The severity of post-surgical CSA-AKI (according to KDIGO stages 1-3). • The duration of post-surgical CSA-AKI. • Necessity of RRT. • Duration of RRT. • The cardiac left and right ventricular function. • The composite of major adverse kidney events (MAKE) that include death, need of dialysis, or sustained impaired renal function within 90±7 d after index surgery (MAKE90). • The incidence of AEs and SAEs.

Conditions and MedDRA coding

Chronic Kidney Disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Individual aged ≥18 years.
2. Male or female.
3. 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.
4. Use of the CPB during surgical intervention expected.
5. Written informed consent obtained from the participant.
6. Understanding of study procedures and willingness to abide by all procedures during the course of the clinical trial.
7. 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.
8. BMI ≥19 kg/m² to ≤40 kg/m².
9. Contraceptive measures for female and male participants.

Exclusion criteria 24

1. CKD stages 4-5 with eGFR <30 ml/min/1.73 m2 pre-surgery as determined by CKD EPI.
2. Previous cardiac surgery.
3. Person has a kidney transplant or another solid organ transplant.
4. Person is scheduled for intermittent or continuous renal replacement therapy (dialysis).
5. Known diagnosis of dementia or other clinical signs of mental illness that will prevent full understanding.
6. Known diagnosis of severe COPD (Gold 3) and/or FEV1 < 1 l/s.
7. Heart failure with severity of symptoms according to NYHA IV.
8. Heart failure with impaired cardiac pump function (LVEF <35%).
9. 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.
10. Clinical signs of a currently active infection including endocarditis requiring antibiotic treatment.
11. Clinical signs of an acute viral infection.
12. 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.
13. 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.
14. Administration of iodinated contrast agent within 24 hours prior to cardiac surgery.
15. 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.
16. 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.
17. Systemic corticosteroid therapy (any dose).
18. Known active chronic inflammatory disease (including, but not limited to, rheumatoid arthritis or systemic lupus erythematosus).
19. Known allergy to SP16 or to other ingredients of the IMP.
20. Person who is not willing to use highly effective contraceptive measures (according to CTFG recommendations v1.2).
21. Pregnant women.
22. Breastfeeding women.
23. Current participation in another interventional clinical study (register studies or non-interventional, observational studies excluded).
24. Employee or direct relative of an employee of the study site, the CRO, or the Sponsor.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Primary safety endpoint: Frequency of AEs and SAEs within 72 h after index surgery.
2. Primary efficacy endpoint: Number of participants who develop CSA-AKI during hospital stay defined by KDIGO stage 1 or higher.

Secondary endpoints 14

1. Highest CSA-AKI stage value according to the stage classification of the KDIGO-AKI in the 7-day period after the index surgery.
2. 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.
3. Necessity of RRT (yes/no)
4. Duration of RRT measured by starting date [yyyy-mmm-dd] and end date [yyyy-mmm-dd]
5. Cardiac function on Day 90±7 d after cardiac index surgery compared to pre surgical assessment (Visit 1) assessed by echocardiography (TTE).
6. 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).
7. NT-proBNP level on Day 1, Day 7, and Day 90±7 d after index surgery compared to pre-surgical assessment on Day 0 (Baseline; Visit 2).
8. 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).
9. All-cause death within 90±7d (3 months) after cardiac index surgery.
10. Sustained impaired renal function defined as ≥25% increase in SCr at Day 90±7 d compared to baseline.
11. Sustained impaired renal function requiring at least one dialysis during the post-surgical interval until Day 90±7 d (end of observation period).
12. Frequency of AE and SAE within 7 days after cardiac index surgery.
13. Frequency of AE and SAE during the observation period.
14. Number of participants with at least one SAE during the observation period.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsklinikum Erlangen AöR

Sponsor organisation

Universitaetsklinikum Erlangen AöR

Address

Maximiliansplatz 2, Innenstadt Innenstadt

City

Erlangen

Postcode

91054

Country

Germany

Scientific contact point

Organisation

Universitaetsklinikum Erlangen AöR

Contact name

Prof. Dr. med Mario Schiffer

Public contact point

Organisation

Universitaetsklinikum Erlangen AöR

Contact name

Prof. Dr. med Mario Schiffer

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications