Patients undergoing invasive cardiac surgery with prolonged perfusion time. This often is associated with potentially life-threatening inflammatory complications due to ischemic periods during surgery both local (Damaged tissue release of nucleotide) and at sites distant from there (e.g. ischemia of the intestinal tract). Alkaline phosphatase detoxifies nucleotides and bacterial toxins and consequently reduces the overall inflammatory insult as demonstrated in the preceding APPIRED I study. Med
Conditions
Interventions
Product Name: bIAP
Product Code: EC 3.1.3.1
Pharmaceutical Form: Solution for injection
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intravenous b
Sponsors
Alloksys Life Sciences BV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or non-pregnant, non-lactating female patients of any race in the ages of >18 years. 2. Patients scheduled for combined aortic valve replacement and CABG surgery 3. Patients who have given written informed consent prior to participation in the trial and who undertake to comply with the protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients who are unwilling or unable to be fully evaluated for follow-up. 2. Patients who have base AP levels at > 125 IU/L, or levels 34.2 µmol/L (> 2.0 mg/dL), ALT (>120) or AST (>135) corresponding to > 3X upper limit of normal. 6. 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. 7. Patients who require pre-operative ventilatory support. 8. Patients who have renal insufficiency (history of creatinine >177µmol/L or >2.0 mg/dL) or chronic renal failure requiring dialysis. 9. Patients who are planned to receive leukocyte-depletion filtration as part of the bypass circuitry. 10. Patients with severe neurological deficits. 11. Patients who have a recent history of drug or alcohol abuse. 12. Patients with a diagnosis of idiopathic thrombocytopenia. 13. 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. 14. 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. 15. Patients who are vegetarians or veganists or those patients that may be expected not to be tolerant for bovine proteins. 16. 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 |
|---|---|
| Main Objective: The objective of this study is to determine the efficacy of bIAP as a prophylactic agent against inflammation-mediated complications from more invasive cardiac surgery, valvular surgery and CABG with cardiopulmonary-bypass time of longer than 1 hour. Primary study endpoint is the postulated reduction of the number of post-surgical SIRS cases in the bIAP-treated patient group as compared to the placebo-treated group. SIRS, in the sense of this study, is indicated by an increased TNF-a level of at least 10 pg/ml above the pre-surgical level, which is normally followed by an increase of IL-6 and IL-8.;Secondary Objective: The incidence of new organ dysfunction within 14 days of surgery will be assessed, next to the duration of organ dysfunction, lengths of organ dysfunction-associated intensive care unit (ICU) and hospital stays, ventilation-assistance and renal failure-dialysis days, volume of blood and blood products infused within 24 hours of surgery, incidence of hospital readmission and 30-day all-cause mortality. Safety will be assessed by incidence and severity of adverse events, changes in physical examination, vital signs and changes in clinical laboratory measurements.;Primary end point(s): Main study primary endpoint is the reduction of post-surgical SIRS in bIAP–treated patients as compared to placebo–treated patients,that is the reduction of incidences of fulminate SIRS responses, indicated by pro-Inflammatory cytokines. The pro-inflammatory cytokine (TNF-a, IL-6 and IL-8) levels will be measured | — |
Countries
Netherlands
Outcome results
None listed