To evaluate the percentage of subjects with AKI within 7 days following on-pump cardiac surgery defined by the KDIGO (Kidney Disease: Improving Global Outcomes) criteria: 1. Increase in baseline (pre-surgery) serum creatinine (SCr) by ≥26.5 μmol/L (≥0.3 mg/dL) within 7 days; OR 2. Increase in baseline SCr to ≥1.5 times baseline, which is known or presumed to have occurred within the first 7 days following surgery; OR 3. Urine output \< 0.5 mL/kg/h for \>6 hours.
This study is a randomized, double-blind, multicenter interventional study to assess safety and efficacy of LSALT peptide versus placebo (matching drug-free saline) in patients undergoing on-pump cardiac surgery. Patients will be followed for safety and efficacy up to Day 28 (EOS), with Day 1 being the day of randomization of study drug administered at least 1 hour prior to induction of anesthesia. A total of 240 patients will be included in the study, 120 patients each will be randomized to LSALT peptide or placebo. This study will be double-blinded with only the pharmacist at the site unblinded for the purpose of preparing drug/placebo for injection. All subjects will undergo tests during the Screening period (window days -14 to Day 1). After satisfying all inclusion and exclusion criteria, the patient will be randomized equally to the following study arms: * LSALT peptide 10 mg IV administered over 1 hour twice daily, every 12 ± 1hour, for 5 days * Placebo IV administered over 1 hour twice daily, every 12 ± 1 hour, for 5 days Study treatment will be initiated pre-operatively on Day 1 and continued for 5 days. Physical examinations, vital signs and urine output will be recorded daily throughout the treatment period and on days 6 and 7. Adverse events will be recorded daily throughout the treatment period, on Days 6, 7, and 28 EOS (Day 28). Kidney function (serum creatinine, serum cystatin C, and BUN), clinical laboratory tests, and other biomarkers will be assessed at baseline (prior to initiation of study drug) and monitored daily throughout the treatment period, on Days 6, 7, and EOS (Day 28). All patients will be maintained on the standard of care (SOC) as per institutional guidelines. Thus, SOC will be followed in each patient with the addition of LSALT peptide or placebo. Subjects will be followed until EOS (Day 28 ± 3 days) to assess renal function as discussed above. An independent Data and Safety Monitoring Board (DSMB) will evaluate patients on a continuing basis for primarily safety assessments. Per the DSMB Charter, the DSMB will meet at least monthly if not more frequently based upon enrollment throughout the study period.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
240
LSALT, a peptide drug with the sequence NH3-LSALTPSPSWLKYKAL-COOH, binds to dipeptidase-1 (DPEP-1) but does not inhibit its biologic enzymatic activity, potentially minimizing off-target or other adverse effects. LSALT peptide inhibits leukocyte recruitment in multiple experimental disease models through the direct inhibition of leukocyte adhesion to DPEP-1 present in lungs, kidney, and liver.
0.9% saline solution
Cumming School of Medicine & Libin Cardiovascular Centre, University of Calgary
Calgary, Alberta, Canada
RECRUITINGRoyal Columbian Hospital
New Westminster, British Columbia, Canada
NOT_YET_RECRUITINGUnity Health Toronto, St. Michael's Hospital
Toronto, Ontario, Canada
RECRUITINGUniversity Health Network, Toronto General Hospital
Toronto, Ontario, Canada
RECRUITINGGazi University
Yenimahalle, Ankara, Turkey (Türkiye)
RECRUITINGKosuyolu High Specialization Training and Research Hospital
Kartal, Istanbul, Turkey (Türkiye)
RECRUITINGErciyes University, Faculty of Medicine - Semiha Kibar Organ Transplant & Dialysis Hospital
Melikgazi, Kayseri, Turkey (Türkiye)
RECRUITINGKocaeli University, Faculty of Medicine Practices and Research Hospital
İzmit, Kocaeli, Turkey (Türkiye)
RECRUITINGSütçü İmam University, Faculty of Medicine
Kahramanmaraş, Onikişubat, Turkey (Türkiye)
RECRUITINGTo evaluate the percentage of subjects with AKI within 7 days following on-pump cardiac surgery defined by the KDIGO (Kidney Disease: Improving Global Outcomes) criteria
1. Increase in baseline (pre-surgery) serum creatinine (SCr) by ≥26.5 μmol/L (≥0.3 mg/dL) within 7 days; OR 2. Increase in baseline SCr to ≥1.5 times baseline, which is known or presumed to have occurred within the first 7 days following surgery; OR 3. Urine output \< 0.5 mL/kg/h for \>6 hours.
Time frame: 7 days
Maximum severity of AKI per patient between treatment groups
1. Stage 1: SCr 1.5 - 1.9 times baseline OR ≥26.5 μmol/L (≥0.3 mg/dL) increase OR urine output \<0.5 mL/kg/hr for 6-12 hours 2. Stage 2: SCr 2.0 - 2.9 times baseline OR urine output \<0.5 mL/kg/h for ≥ 12 hours 3. Stage 3: SCr ≥3.0 times baseline OR increase in SCr of ≥26.5 μmol/L (≥0.3 mg/dL) to ≥353.6 μmol/L (≥4.0 mg/dL) OR initiation of renal replacement therapy (RRT) OR urine output \<0.3 mL/kg/h for ≥24 hours OR anuria for ≥12 hours.
Time frame: 7 days
Time to mild, moderate, and severe AKI per patient between treatment groups
Time frame: 7 days
Need for RRT within the first 7 days following surgery
Time frame: 7 days
Need for RRT at any time during the 28-day study
Time frame: 28 days
Duration of AKI at 28 days (EOS)
Duration of AKI is defined as the number of days from start of AKI per KDIGO criteria to onset of resolution
Time frame: 28 days
Kidney function (SCr, eGFR) at 28 days (EOS)
Time frame: 28 days
28-day all-cause mortality
Time frame: 28 days
Composite of death, need for RRT, and/or persistent impaired renal function from baseline (MAKE [major adverse kidney event] criteria) at Day 28 (EOS)
Time frame: 28 days
ICU length of stay (in days)
Time frame: 28 days
Hospitalization length of stay (in days)
Time frame: 28 days
Incidence of new-onset lung or liver disorders following surgery
Time frame: 28 days
Change in baseline serum cystatin C, serum NGAL, serum IP-10, serum IL-1beta, serum IL-6, and serum IL-18 biomarker levels
Time frame: 28 days
Changes in urinary TIMP-2 and IGFBP7 biomarker and serum NGAL, AGT, and IL-18 biomarker levels
Biomarkers will be measured at baseline and days 1, 3, 5, and 7
Time frame: 7 days
Development of serum anti-drug antibodies levels throughout the study
Anti-drug antibodies will be measured at baseline (Day 1 prior to the first dose of study medication) and at days 1, 2, 3, 4, 5 and day 28 (EOS)
Time frame: 28 days
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