Efficacy and Safety of Bovine Intestinal Alkaline Phosphatase (bIAP) During Heart Surgery

Study Overview
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Brief Summary
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This multi-centre prospective, randomised, double-blind, placebo-controlled study is designed to evaluate the efficacy and safety of bovine intestinal alkaline phosphatase (bIAP) in reducing the pro-inflammatory post-surgical responses and thereby preserving organ functions in patients undergoing invasive cardiac surgery: combined aortic valve replacement and coronary artery bypass grafting.

Official Title
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A Randomized, Double-blind, Placebo-controlled Phase IIIa Study on bIAP, an Anti-inflammatory Moiety, in Patients Undergoing Combined Aortic Valve Replacement and Coronary Artery Bypass Grafting

Conditions
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Inflammation

Intervention / Treatment
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* Drug: bIAP bolus and 8h infusion
* Drug: placebo bolus and 8h infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or non-pregnant, non-lactating female patients of any race in the ages of >18 years. Patients scheduled for combined aortic valve replacement and CABG surgery. Patients who have given written informed consent prior to participation in the trial and who undertake to comply with the protocol. Exclusion Criteria: Patients who are unwilling or unable to be fully evaluated for follow-up. Patients who have base AP levels at > 125 IU/L, or levels < 30 IU/L (ammediol, DEA (diethanolamine) units) Patients who show pre-operative infections or who are suspected of endocarditis or systemic infection. Patients who refuse to accept medically-indicated blood products. Patients who have evidence of significant hepatic disease, including history of clinical signs or laboratory values of total bilirubin > 34.2 µmol/L (> 2.0 mg/dL), ALT (>120) or AST (>135) corresponding to > 3X upper limit of normal. Patients who received investigational drugs in the 30 days prior to study drug administration, or are currently participating in a study during which the administration of investigational drugs within one month is anticipated. Patients who require pre-operative ventilatory support. Patients who have renal insufficiency (history of creatinine >177mol/L or >2.0 mg/dL) or chronic renal failure requiring dialysis. Patients who are planned to receive leukocyte-depletion filtration as part of the bypass circuitry. Patients with severe neurological deficits. Patients who have a recent history of drug or alcohol abuse. Patients with a diagnosis of idiopathic thrombocytopenia. Patients with a history of cancer who have received chemotherapy or radiation therapy within the past 3 months. Patients receiving only adjuvant hormonal therapy are not excluded. Patients who are scheduled to receive stress doses of glucocorticoids (i.e., doses >2 mg/kg/day of methylprednisolone or equivalent) prior to, during or following surgery. Patients who are vegetarians or veganists or those patients that may be expected not to be tolerant for bovine proteins. Patients who are, in the opinion of the investigator, unsuitable for the study. A well-documented screening log should be present in the clinic.

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Active Comparator: bIAP<br>intravenous as a bolus of bIAP (alkaline phosphatase, 1000 IU) just prior to surgery followed by a 40 IU/kg bIAP infusion during the first 8 hours post surgery. | Drug: bIAP bolus and 8h infusion<br>* intravenous as a bolus of bIAP (bovine intestinal alkaline phosphatase, 1000 IU) just prior to surgery followed by a 40 IU/kg bIAP infusion during the first 8 hours post surgery.<br>|
| Placebo Comparator: placebo<br>intravenous as a bolus just prior to surgery followed by an infusion during the first 8 hours post surgery. | Drug: placebo bolus and 8h infusion<br>* intravenous as a bolus just prior to surgery followed by an infusion during the first 8 hours post surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TNF-alpha | as indicator of post-surgical inflammatory response | one day before till 5 days post surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of new organ dysfunctions |  | till 30 days post surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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valve replacement, CABG, SIRTS, Combined aortic valve replacement and CABG surgery