Preventing Systemic Inflammation After Cardiac Surgery With Alkaline Phosphatase

Study Overview
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Brief Summary
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Study should demonstrate that alkaline phosphatase reduces the incidence and extent of acute kidney injury after cardiopulmonary bypass (CPB) as defined by the AKIN criteria.

Detailed Description
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After cardiac surgery under cardiopulmonary bypass (CPB) patients often show impairments of the immune system. Compared to placebo, CPB patients given alkaline phosphatase will have reduced composite endpoint of acute kidney injury (AKI), late extubation, gastrointestinal or neurological complications within 7 days and AKI within 90 days.

Official Title
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Preventing Oxidative Stress-induced Ischemic Injury- and Systemic Inflammation Complications During and After Invasive Cardiac Surgery With Alkaline Phosphatase (APPIRED III)

Conditions
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Systemic Inflammation, Cardiopulmonary-bypass

Intervention / Treatment
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* Drug: bRESCAP
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Undergoing cardiac surgery with planned cardiopulmonary bypass Additive Euroscore II ≥ 3 OR at least 3 surgical cardiac interventions are planned Ability to provide informed consent (not incapacitated) Exclusion Criteria: Already on renal replacement therapy Patients with chronic kidney disease defined as estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2 [ CKD stage > 3 ] Patients who are pregnant or lactating Concurrent enrollment in another clinical trial Known allergic reaction to bovine alkaline phosphatase or patient is vegetarian or vegan Patients with ongoing infections or current use of steroids Patients with high-risk emergency surgery or with follow-up procedures already planned at admission (like e.g. TEVAR)

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: bRESCAP<br>Bolus of 1000 IU of bovine intestinal alkaline phosphatase on induction of anaesthesia, followed by an infusion with a sum of 10,000 IU/day over the next 24, 48, or 96 hours. | Drug: bRESCAP<br>* intravenous application before, during, and for 24, 48, or 96 hours after heart surgery<br>|
| Placebo Comparator: Placebo<br>Bolus of of media on induction of anaesthesia, followed by an infusion of media over the next 24, 48, or 96 hours. | Drug: placebo<br>* intravenous application before, during, and for 24, 48, or 96 hours after heart surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with acute kidney injury | AKIN criteria: Rise in serum creatinine of by 0.3 mg/dl or 26 µmol/L in 48 hours/ a percentage increase in the serum creatinine concentration of more than 50 percent or a drop in urine output to 0.5 ml/kg/hour for 6 hours | 90 days | 
| reach haemodynamic stability | Demonstrate that RESCAP® intervention reduces the time at ICU to reach haemodynamic stability | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cost-related outcome | Cost (SGD) incurred on renal replacement therapy, ICU and hospital stay | 30 days | 
| levels of a set of inflammatory markers | IL-6, IL-8, IL-10, TNF-alpha | 4 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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side-effects, alkaline phosphatase, heart-lung machine