Inflammation
Conditions
Keywords
valve replacement, CABG, SIRTS, Combined aortic valve replacement and CABG surgery
Brief summary
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.
Interventions
DRUGbIAP bolus and 8h infusion
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.
DRUGplacebo bolus and 8h infusion
intravenous as a bolus just prior to surgery followed by an infusion during the first 8 hours post surgery.
Sponsors
Aix Scientifics
Alloksys Life Sciences B.V.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| TNF-alpha | one day before till 5 days post surgery | as indicator of post-surgical inflammatory response |
Secondary
| Measure | Time frame |
|---|---|
| incidence of new organ dysfunctions | till 30 days post surgery |
Countries
Netherlands
Outcome results
None listed