Preventing Systemic Inflammation After Cardiac Surgery With Alkaline Phosphatase

Systemic Inflammation Clinical Trial

— 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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03050476
• Other study ID #: NUH-ALS-2015-04
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: November 1, 2017
• Est. completion date: March 31, 2026

Study information

• Verified date: April 2024
• Source: Alloksys Life Sciences B.V.
• Contact: Ruud Brands, PhD
• Phone: +31 647 228 395
• Email: ruud[@]alloksys.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1250
• Est. completion date: March 31, 2026
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Cardiopulmonary-bypass
• Inflammation
• Systemic Inflammation

Intervention

Drug:
• RESCAP®
intravenous application before, during, and for 24 or 96 hours after heart surgery
• placebo
intravenous application before, during, and for 24 or 96 hours after heart surgery

Locations

Country	Name	City	State
Australia	Dept. Cardiothoracic Surgery , Monash Medical Centre	Clayton	Melbourne
Austria	Division of Cardiac Surgery, Department of Surgery, LKH Medical University of Graz	Graz
Austria	MedUniWien / AKH-Wien	Wien
Belgium	Department of Intensive Care, CHU Saint-Pierre, Université Libre de Bruxelles (ULB)	Brussels
Belgium	Department of Intensive Care, Hôpital Universitaire de Bruxelles (HUB)	Brussels
Belgium	Hospital ZOL	Genk
Belgium	Dept. of Anesthesia and Intensive Care, AZ Maria Middelares	Gent
Belgium	Jessa Ziekenhuis,Campus Virga Jesse	Hasselt
Germany	Klinik für Herzchirurgie, Universitätsklinik	Leipzig
Germany	German Heart Centre Munich, Dept.Cardio-Vascular Surgery	Munich	Bavaria
Italy	Policlinico Gemelli, Institute Cardiology	Roma
Italy	U.O.C. Cardiochirurgia e Trapianti di Cuore, Azienda Ospedaliera San Camillo Forlanini	Roma
Malaysia	Institut Jantung Negara (IJN , Natl. Heart Inst.)	Kuala Lumpur
Netherlands	Catharina Ziekenhuis, Cathreine R&D, Heartcentre	Eindhoven
Netherlands	Dept. Cardiothoracic Surgery, Maastricht University Medical Centre	Maastricht	Limburg
Portugal	Hospital de Santa Marta	Lisboa
Russian Federation	State Autonomous Healthcare Institution "Interregional Clinical Diagnostic Center"	Kazan
Russian Federation	Federal State Budgetary Military Educational Institution of the Higher Education	Saint Petersburg
Russian Federation	Almazov Heart Center	St Petersburg
Singapore	National University Hospital (NUH),	Singapore
Spain	Jefe de Servicio de Cirugía Cardiovascular, Hospital Universitario La Princesa	Madrid

Sponsors (2)

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

Countries where clinical trial is conducted

Australia,  Austria,  Belgium,  Germany,  Italy,  Malaysia,  Netherlands,  Portugal,  Russian Federation,  Singapore,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	90 days
Primary	reach haemodynamic stability	Demonstrate that RESCAP® intervention reduces the time at ICU to reach haemodynamic stability	7 days
Secondary	cost-related outcome	Cost (SGD) incurred on renal replacement therapy, ICU and hospital stay	30 days
Secondary	levels of a set of inflammatory markers	IL-6, IL-8, IL-10, IL-17, TNF-alpha	4 days