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

Inflammation Clinical Trial

— APPIRED-II  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01144611
• Other study ID #: ALS-002-2009
• Secondary ID: 2009-010191-19
• Status: Completed
• Phase: Phase 3
• First received: June 14, 2010
• Last updated: September 19, 2016
• Start date: April 2010
• Est. completion date: December 2013

Study information

• Verified date: June 2011
• Source: Alloksys Life Sciences B.V.
• Contact: n/a
• Is FDA regulated: No
• Health authority: European Union: European Medicines Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Inflammation

Intervention

Drug:
• bIAP 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.
• placebo bolus and 8h infusion
intravenous as a bolus just prior to surgery followed by an infusion during the first 8 hours post surgery.

Locations

Country	Name	City	State
Netherlands	Catharina Ziekenhuis, Dept. CardioThoracic Surgery	Eindhoven

Sponsors (2)

Lead Sponsor	Collaborator
Alloksys Life Sciences B.V.	Aix Scientifics

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	TNF-alpha	as indicator of post-surgical inflammatory response	one day before till 5 days post surgery	No
Secondary	incidence of new organ dysfunctions		till 30 days post surgery	No