Back to resultsPreventing Systemic Inflammation After Cardiac Surgery With Alkaline Phosphatase (APPIRED-III)
Primary Purpose
Systemic Inflammation, Cardiopulmonary-bypass
Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
bRESCAP
placebo
Sponsored by
About this trial
This is an interventional prevention trial for Systemic Inflammation focused on measuring side-effects, heart-lung machine, alkaline phosphatase
Eligibility Criteria
Inclusion Criteria:
- Undergoing cardiac surgery with planned cardiopulmonary bypass
- Additive Euroscore II ≥ 3 OR at least 3 surgical cardiac interventions are planned
- Ability to provide informed consent (not incapacitated)
Exclusion Criteria:
- Already on renal replacement therapy
- Patients with chronic kidney disease defined as estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2 [ CKD stage > 3 ]
- Patients who are pregnant
- Concurrent enrollment in another clinical trial
- Known allergic reaction to bovine alkaline phosphatase or patient is vegetarian or vegan
- Patients with ongoing infections or current use of steroids
Sites / Locations
- Dept. Cardiothoracic Surgery , Monash Medical Centre
- MedUniWien / AKH-WienRecruiting
- Hospital ZOL
- Dept. of Anesthesia and Intensive Care, AZ Maria MiddelaresRecruiting
- Jessa Ziekenhuis,Campus Virga JesseRecruiting
- German Heart Centre Munich, Dept.Cardio-Vascular Surgery
- Klinik für Herzchirurgie, Universitätsklinik
- Policlinico Gemelli, Institute Cardiology
- Institut Jantung Negara (IJN , Natl. Heart Inst.)
- Dept. Cardiothoracic Surgery, Maastricht University Medical CentreRecruiting
- Catharina Ziekenhuis, Cathreine R&D, HeartcentreRecruiting
- Hospital de Santa Marta
- State Autonomous Healthcare Institution "Interregional Clinical Diagnostic Center"Recruiting
- Federal State Budgetary Military Educational Institution of the Higher EducationRecruiting
- Almazov Heart CenterRecruiting
- National University Hospital (NUH),Recruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
bRESCAP
Placebo
Arm Description
Bolus of 1000 IU of bovine intestinal alkaline phosphatase on induction of anaesthesia, followed by an infusion with a sum of 10,000 IU/day over the next 24, 48, or 96 hours.
Bolus of of media on induction of anaesthesia, followed by an infusion of media over the next 24, 48, or 96 hours.
Outcomes
Primary Outcome Measures
Number of patients with acute kidney injury
AKIN criteria: Rise in serum creatinine of by 0.3 mg/dl or 26 µmol/L in 48 hours/ a percentage increase in the serum creatinine concentration of more than 50 percent or a drop in urine output to 0.5 ml/kg/hour for 6 hours
reach haemodynamic stability
Demonstrate that RESCAP® intervention reduces the time at ICU to reach haemodynamic stability
Secondary Outcome Measures
cost-related outcome
Cost (SGD) incurred on renal replacement therapy, ICU and hospital stay
levels of a set of inflammatory markers
IL-6, IL-8, IL-10, TNF-alpha
Full Information
NCT ID
NCT03050476
First Posted
January 24, 2017
Last Updated
February 1, 2023
Sponsor
Alloksys Life Sciences B.V.
Collaborators
Aix Scientifics
1. Study Identification
Unique Protocol Identification Number
NCT03050476
Brief Title
Preventing Systemic Inflammation After Cardiac Surgery With Alkaline Phosphatase
Acronym
APPIRED-III
Official Title
Preventing Oxidative Stress-induced Ischemic Injury- and Systemic Inflammation Complications During and After Invasive Cardiac Surgery With Alkaline Phosphatase (APPIRED III)
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 1, 2017 (Actual)
Primary Completion Date
September 30, 2025 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alloksys Life Sciences B.V.
Collaborators
Aix Scientifics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Study should demonstrate that alkaline phosphatase reduces the incidence and extent of acute kidney injury after cardiopulmonary bypass (CPB) as defined by the AKIN criteria.
Detailed Description
After cardiac surgery under cardiopulmonary bypass (CPB) patients often show impairments of the immune system. Compared to placebo, CPB patients given alkaline phosphatase will have reduced composite endpoint of acute kidney injury (AKI), late extubation, gastrointestinal or neurological complications within 7 days and AKI within 90 days.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Systemic Inflammation, Cardiopulmonary-bypass
Keywords
side-effects, heart-lung machine, alkaline phosphatase
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
1250 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
bRESCAP
Arm Type
Experimental
Arm Description
Bolus of 1000 IU of bovine intestinal alkaline phosphatase on induction of anaesthesia, followed by an infusion with a sum of 10,000 IU/day over the next 24, 48, or 96 hours.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Bolus of of media on induction of anaesthesia, followed by an infusion of media over the next 24, 48, or 96 hours.
Intervention Type
Drug
Intervention Name(s)
bRESCAP
Intervention Description
intravenous application before, during, and for 24, 48, or 96 hours after heart surgery
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
intravenous application before, during, and for 24, 48, or 96 hours after heart surgery
Primary Outcome Measure Information:
Title
Number of patients with acute kidney injury
Description
AKIN criteria: Rise in serum creatinine of by 0.3 mg/dl or 26 µmol/L in 48 hours/ a percentage increase in the serum creatinine concentration of more than 50 percent or a drop in urine output to 0.5 ml/kg/hour for 6 hours
Time Frame
90 days
Title
reach haemodynamic stability
Description
Demonstrate that RESCAP® intervention reduces the time at ICU to reach haemodynamic stability
Time Frame
7 days
Secondary Outcome Measure Information:
Title
cost-related outcome
Description
Cost (SGD) incurred on renal replacement therapy, ICU and hospital stay
Time Frame
30 days
Title
levels of a set of inflammatory markers
Description
IL-6, IL-8, IL-10, TNF-alpha
Time Frame
4 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Undergoing cardiac surgery with planned cardiopulmonary bypass
Additive Euroscore II ≥ 3 OR at least 3 surgical cardiac interventions are planned
Ability to provide informed consent (not incapacitated)
Exclusion Criteria:
Already on renal replacement therapy
Patients with chronic kidney disease defined as estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2 [ CKD stage > 3 ]
Patients who are pregnant or lactating
Concurrent enrollment in another clinical trial
Known allergic reaction to bovine alkaline phosphatase or patient is vegetarian or vegan
Patients with ongoing infections or current use of steroids
Patients with high-risk emergency surgery or with follow-up procedures already planned at admission (like e.g. TEVAR)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ruud Brands, PhD
Phone
+31 30 253 3615
Email
ruud@alloksys.com
First Name & Middle Initial & Last Name or Official Title & Degree
Eike G Fischer, PhD
Phone
+49 241 4500 358
Email
eike@aix-scientifics.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ruud Brands, PhD
Organizational Affiliation
Alloksys Life Sciences BV . President
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Theodoros Kofidis, Prof.Dr.
Organizational Affiliation
National University Hospital (NUH), Singapore
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dept. Cardiothoracic Surgery , Monash Medical Centre
City
Clayton
State/Province
Melbourne
ZIP/Postal Code
VIC 3168
Country
Australia
Individual Site Status
Terminated
Facility Name
MedUniWien / AKH-Wien
City
Wien
ZIP/Postal Code
1090
Country
Austria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dominik Wiedemann, Prof. Dr.
Phone
+43-1-40400-6966
Email
dominik.wiedemann@meduniwien.ac.at
First Name & Middle Initial & Last Name & Degree
Günther Laufer, Univ.Prof.Dr
Email
guenther.laufer@meduniwien.ac.at
Facility Name
Hospital ZOL
City
Genk
ZIP/Postal Code
3600
Country
Belgium
Individual Site Status
Suspended
Facility Name
Dept. of Anesthesia and Intensive Care, AZ Maria Middelares
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jan Heerman, Dr.
Phone
+32 9 246 17 21
Email
Jan.Heerman@AZMMSJ.be
Facility Name
Jessa Ziekenhuis,Campus Virga Jesse
City
Hasselt
ZIP/Postal Code
3500
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Abdullah Kaya, Dr.
Phone
+32 11 -33 71 00
Email
a_kaya33@hotmail.com
Facility Name
German Heart Centre Munich, Dept.Cardio-Vascular Surgery
City
Munich
State/Province
Bavaria
ZIP/Postal Code
80636
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hendrik Ruge, Dr.
Phone
+49 89 1218 1510
Email
ruge@dhm.mhn.de
Facility Name
Klinik für Herzchirurgie, Universitätsklinik
City
Leipzig
ZIP/Postal Code
04289
Country
Germany
Individual Site Status
Suspended
Facility Name
Policlinico Gemelli, Institute Cardiology
City
Roma
ZIP/Postal Code
00168
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Massimo Massetti, Prof.MD
Phone
+39 06 - 3015 - 8762
Email
Massimo.Massetti@unicatt.it
Facility Name
Institut Jantung Negara (IJN , Natl. Heart Inst.)
City
Kuala Lumpur
ZIP/Postal Code
50400
Country
Malaysia
Individual Site Status
Terminated
Facility Name
Dept. Cardiothoracic Surgery, Maastricht University Medical Centre
City
Maastricht
State/Province
Limburg
ZIP/Postal Code
6229 HX
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Roberto Lorusso, Prof. Dr.
Phone
+31 43 387 1125
Email
roberto.lorusso@mumc.nl
Facility Name
Catharina Ziekenhuis, Cathreine R&D, Heartcentre
City
Eindhoven
ZIP/Postal Code
5623 EJ
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
M.E.S.H. Tan, MD
Phone
+31 40 - 239 8360
Email
erwin.tan@catharinaziekenhuis.nl
First Name & Middle Initial & Last Name & Degree
Esther van Dooren
Email
Esther.v.Dooren@catharinaziekenhuis.nl
Facility Name
Hospital de Santa Marta
City
Lisboa
ZIP/Postal Code
1169-024
Country
Portugal
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
José Fragata, Prof.MD PhD
Phone
+351 21 359 41 06
Email
jigFragata@gmail.com
First Name & Middle Initial & Last Name & Degree
Pedro Coelho, MD
Email
pedropirescoelho@gmail.com
Facility Name
State Autonomous Healthcare Institution "Interregional Clinical Diagnostic Center"
City
Kazan
ZIP/Postal Code
420101
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Roin K Dzhordzhikiya, Dr
Phone
+7 (843)- 291-10-00
Email
roink@mail.ru
Facility Name
Federal State Budgetary Military Educational Institution of the Higher Education
City
Saint Petersburg
ZIP/Postal Code
194044
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gennadiy Khubulava, Dr.
Phone
+7 (812)-575-08-50
Email
ggkh07trail@mail.ru
Facility Name
Almazov Heart Center
City
St Petersburg
ZIP/Postal Code
197341
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexandra Konradi, Prof dr
Phone
+7 812 702-68-16
Email
konradi@almazovcentre.ru
First Name & Middle Initial & Last Name & Degree
Olga Bolsakova, Prof
Phone
+7 (812) 702-37-41
Email
oobolshakova@yahoo.com
Facility Name
National University Hospital (NUH),
City
Singapore
ZIP/Postal Code
119228
Country
Singapore
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Theodoros Kofidis, Prof.Dr.
Phone
+65 677 - 22059
Email
Theodoros@nuhs.edu.sg
First Name & Middle Initial & Last Name & Degree
Ram Ramanathan
Email
Ram_Ramanathan@nuhs.edu.sg
12. IPD Sharing Statement
Plan to Share IPD
No
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Preventing Systemic Inflammation After Cardiac Surgery With Alkaline Phosphatase
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