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

Primary Purpose

Inflammation

Status
Completed
Phase
Phase 3
Locations
Netherlands
Study Type
Interventional
Intervention
bIAP bolus and 8h infusion
placebo bolus and 8h infusion
Sponsored by
Alloksys Life Sciences B.V.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Inflammation focused on measuring valve replacement, CABG, SIRTS, Combined aortic valve replacement and CABG surgery

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Catharina Ziekenhuis, Dept. CardioThoracic Surgery

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

bIAP

placebo

Arm Description

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.

intravenous as a bolus just prior to surgery followed by an infusion during the first 8 hours post surgery.

Outcomes

Primary Outcome Measures

TNF-alpha
as indicator of post-surgical inflammatory response

Secondary Outcome Measures

incidence of new organ dysfunctions

Full Information

First Posted
June 14, 2010
Last Updated
September 19, 2016
Sponsor
Alloksys Life Sciences B.V.
Collaborators
Aix Scientifics
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1. Study Identification

Unique Protocol Identification Number
NCT01144611
Brief Title
Efficacy and Safety of Bovine Intestinal Alkaline Phosphatase (bIAP) During Heart Surgery
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2011
Overall Recruitment Status
Completed
Study Start Date
April 2010 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
December 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alloksys Life Sciences B.V.
Collaborators
Aix Scientifics

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Inflammation
Keywords
valve replacement, CABG, SIRTS, Combined aortic valve replacement and CABG surgery

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
53 (Actual)

8. Arms, Groups, and Interventions

Arm Title
bIAP
Arm Type
Active Comparator
Arm Description
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.
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
intravenous as a bolus just prior to surgery followed by an infusion during the first 8 hours post surgery.
Intervention Type
Drug
Intervention Name(s)
bIAP bolus and 8h infusion
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
placebo bolus and 8h infusion
Intervention Description
intravenous as a bolus just prior to surgery followed by an infusion during the first 8 hours post surgery.
Primary Outcome Measure Information:
Title
TNF-alpha
Description
as indicator of post-surgical inflammatory response
Time Frame
one day before till 5 days post surgery
Secondary Outcome Measure Information:
Title
incidence of new organ dysfunctions
Time Frame
till 30 days post surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
M.Erwin S.H. Tan, Prof.Dr.med.
Organizational Affiliation
Catharina Ziekenhuis, Dept. CardioThoracic Surgery
Official's Role
Principal Investigator
Facility Information:
Facility Name
Catharina Ziekenhuis, Dept. CardioThoracic Surgery
City
Eindhoven
ZIP/Postal Code
5623 EJ
Country
Netherlands

12. IPD Sharing Statement

Learn more about this trial

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

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