Autologous modified white blood cell therapy for acute kidney injury after heart surgery

Modified Autologous Leukocyte Cells for the Treatment of Acute Kidney Injury After Cardiac Surgery

This test gives people who develop acute kidney injury within 48 hours after cardiac surgery a single dose of their own modified white blood cells or a placebo to see if it helps kidneys recover faster and is safe.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 98 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: M2RLAB SL (industry)
• Locations: 1 site (Barcelona, Catalonia)
• Trial ID: NCT07052513 on ClinicalTrials.gov

What this trial studies

This is a Phase II, randomized, placebo-controlled, single-blind trial that enrolls adults who develop acute kidney injury within 48 hours after elective valvular or coronary surgery with extracorporeal circulation. Participants are randomized 1:1 to a single administration of autologous modified leukocyte cells (M2RLAB 001) or a look-alike placebo, with about 49 subjects per arm. The study will compare time to kidney function recovery and monitor safety and adverse events related to the cell therapy. The approach is based on the immunomodulatory properties of modified leukocytes as a possible way to limit injury and speed recovery when no established pharmacologic treatments exist.

Who should consider this trial

Good fit: Adults (over 18) undergoing elective valve or coronary cardiac surgery with extracorporeal circulation who develop AKI within 48 hours postoperatively and meet the AKIN criteria or preoperative risk thresholds are the intended participants.

Not a fit: Patients without postoperative AKI, those with AKI diagnosed more than 48 hours after surgery, or those with end-stage kidney disease on chronic dialysis are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, the therapy could shorten the time to kidney recovery after cardiac surgery and reduce complications from acute kidney injury.

How similar studies have performed: Early-phase cell‑therapy studies for kidney injury have shown promising safety signals and occasional renal benefit, but efficacy is not yet established in larger trials.

Eligibility criteria

Inclusion Criteria:

1. Male or female participants older than 18 years of age, being able to understand and sign the Informed Consent.
2. Participants undergoing elective valvular and/or coronary cardiac surgery performed with extracorporeal circulation.
3. Participants must meet one of the following two criteria:

   1. Present pre-operative AKI risk more or equal to 30 percent according to the Leicester Cardiosurgery scale, in case the participants had signed the IC before.
   2. Participants that had signed the IC within 12 hours after the AKI diagnosis.
4. Present AKI within the first 48 hours post cardiac surgery in one of the following classifications defined by the AKIN scale (Acute Kidney Injury Network):

   AKIN 1: An increase in serum creatinine by at least 0.3 mg/dL (more or equal to 26.4 micromol/L) from baseline, or an increase to more or equal to 150-200 percent (corresponding to a 1.5- to 2-fold increase) from baseline. In addition, the participant must have a positive acute tubular necrosis score within the first 48 hours post cardiac surgery, defined as the presence of at least 3 of the following 4 scenarios: Sodium excretion fraction more than 2 percent, urinary osmolality lower than 400 mOsm/kg, urine sodium more than 40 mmol/L, presence of shock or nephrotoxic agents.

   AKIN 2: An increase in serum creatinine to more than 200 percent and up to a maximum of 300 percent (corresponding to an increase of more than 2 and up to 3 times) over baseline.

   AKIN 3: An increase in serum creatinine to more than 300 percent (corresponding to more than 3-fold increase) over baseline, or an increase in serum creatinine levels to more or equal to 4.0 mg/dl (more or equal to 354 micromol/l) with an acute increase of at least 0.5 mg/dl (44 micromol/l).
5. In the case of women or men of childbearing age, for safety, those who undertake to follow the contraceptive measures required from their discharge from hospital until the end of their participation in the clinical trial.

Exclusion Criteria:

1. Chronic Kidney Disease (CKD) in stage IV or V (glomerular filtration rate \[GFR\] less than 30 ml/min).
2. AKI one month prior to heart surgery.
3. Participants who have previously undergone renal replacement therapy.
4. Participants who, due to their clinical situation (hemodynamic instability, oliguria, current or anticipated volume overload) are scheduled to start renal replacement therapy within the next 48 hours after AKI diagnosis.
5. Interstitial glomerulonephritis or vasculitis.
6. Pregnancy.
7. Women in breastfeeding period
8. Renal transplant history.
9. Endocarditis.
10. Participants with mechanical assistance devices: extracorporeal membrane oxygenation (ECMO), left ventricular assist device (LVAD), right ventricular assist device (RVAD), intra-aortic balloon pumps (IABP).
11. Known severe ventricular dysfunction (left ventricular ejection fraction \[LVEF\] less than 30 percent).
12. Post-surgical septic infectious condition.
13. Clinically significant anemia with hemoglobin values below 100g/l.
14. Positive serology for hepatitis C virus (HCV), hepatitis B virus antigen (HBSAg), human immunodeficiency virus (HIV) or syphilis (by RPR: Rapid Plasma Reagin). This criterion will be assessed once it has been confirmed that the participant has developed AKI.
15. Participants enrolled in another clinical trial testing.

Where this trial is running

Barcelona, Catalonia

• Hospital Clinic of Barcelona — Barcelona, Catalonia, Spain (RECRUITING)

Study contacts

• Principal investigator: Esteban Poch López de Briñas — Hospital Clinic of Barcelona
• Study coordinator: Pablo García de la Riva Mestre

Conditions: Acute Kidney Injury, Cardiac Surgery, Thoracic Surgery, Acute Renal Insufficiency, Acute Renal Injury, Major Adverse Kidney Event, Autologous Leukocyte Cells, Leukocyte Cells