Preventing Systemic Inflammation after Cardiac surgery by Alkaline Phosphatase (APPIRED III)

Preventing Oxidative stress-induced Ischemic Injury and Systemic Inflammation complications during and after invasive Cardiac surgery with Alkaline Phosphatase (APPIRED III) - APPIRED III

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2016-002663-33-NL

Enrollment

1250

Registered

2017-04-19

Start date

2017-08-22

Completion date

Unknown

Last updated

2025-01-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

systemic inflammation as side-effect of heart-lung machine during cardiac surgery MedDRA version: 20.0 Level: LLT Classification code 10017501 Term: Functional disturbances following cardiac surgery System Organ Class: 100000004863 MedDRA version: 20.0 Level: LLT Classification code 10062357 Term: SIRS System Organ Class: 100000004867

Interventions

Product Name: Alkaline Phosphatase (RESCAP®) Product Code: EC 3.1.3.1 , CAS-Nummer: 9001-78-9 Pharmaceutical Form: Solution for injection/infusion INN or Proposed INN: bovine alkaline phosphatase

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: A potential subject must meet all of the following criteria to participate in the study: 1. > 21 years of age (legal adult in Singapore) 2. Undergoing cardiac surgery with planned cardiopulmonary bypass 3. EuroSCORE II >= 3 4. Ability to provide informed consent (not incapacitated) 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 625 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 625

Exclusion criteria

Exclusion criteria: Any subjects meeting the following criteria at baseline will be excluded: 1. Already on renal replacement therapy 2. Patients with chronic kidney disease defined as estimated glomerular filtration rate [eGFR] 3] 3. Patients who are pregnant 4. Concurrent enrolment in another clinical trial 5. Known allergic reaction to bovine alkaline phosphatase or patient is vegetarian, vegan, or does not consume any bovine meat products (beef) that is, the patient may not be tolerant for bovine proteins 6. Patients with ongoing infections or current use of steroids.

Design outcomes

Primary

Measure	Time frame
Main Objective: Demonstrate that alkaline phosphatase reduces the incidence and extent of acute kidney injury after cardiopulmonary bypass as defined by the 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 =50 percent 10 or •A drop in urine output to 0.5 ml/kg/hour for 6 hours Demonstrate that alkaline phosphatase reduces overall morbidity and mortality - time to extubation [ defined as removal of endotracheal tube] - reduce GI Complications : defined as demonstrable nasogastric bleeding > 12 hours , malena or positive faecal occult blood - reduce Neuro Complications : defined as focal neurological deficit of central origin lasting more than 72 hours demonstrable on a CT scan.;Secondary Objective: 1.Measure cost-related outcomes associated to CPB and AP intervention including a) the incidence of renal replacement therapy, b) duration of renal replacement therapy, c) days spent in the ICU and hospital, and d) the incidence of arrhythmias in the two groups 2. Compare plasma levels of a set of inflammatory markers (IL-6, IL-8, IL-10, TNF-alpha) and increase endogenous alkaline phosphatase levels and kidney function markers (IL18, NGAL, TIMP-2, GFR) in the control and AP treated groups. ;Primary end point(s): Efficacy We will have two efficacy endpoints that will be independently monitored by the data-safety monitoring board: •Stop administering placebo but continue with experimental drug if AKI (defined by AKIN) is significantly lower in the experimental group •Stop administering placebo but continue with experimental drug if mortality is significantly lower in the experimental group. Given the results of previous studies in sepsis patients, we anticipate that the greatest benefits will be seen in the prevention of AKI in the experimental group. If these benefits reach a level of statistical significance and are considered clinically relev	—

Measure

Time frame

Main Objective: Demonstrate that alkaline phosphatase reduces the incidence and extent of acute kidney injury after cardiopulmonary bypass as defined by the 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 =50 percent 10 or •A drop in urine output to 0.5 ml/kg/hour for 6 hours Demonstrate that alkaline phosphatase reduces overall morbidity and mortality - time to extubation [ defined as removal of endotracheal tube] - reduce GI Complications : defined as demonstrable nasogastric bleeding > 12 hours , malena or positive faecal occult blood - reduce Neuro Complications : defined as focal neurological deficit of central origin lasting more than 72 hours demonstrable on a CT scan.;Secondary Objective: 1.Measure cost-related outcomes associated to CPB and AP intervention including a) the incidence of renal replacement therapy, b) duration of renal replacement therapy, c) days spent in the ICU and hospital, and d) the incidence of arrhythmias in the two groups 2. Compare plasma levels of a set of inflammatory markers (IL-6, IL-8, IL-10, TNF-alpha) and increase endogenous alkaline phosphatase levels and kidney function markers (IL18, NGAL, TIMP-2, GFR) in the control and AP treated groups. ;Primary end point(s): Efficacy We will have two efficacy endpoints that will be independently monitored by the data-safety monitoring board: •Stop administering placebo but continue with experimental drug if AKI (defined by AKIN) is significantly lower in the experimental group •Stop administering placebo but continue with experimental drug if mortality is significantly lower in the experimental group. Given the results of previous studies in sepsis patients, we anticipate that the greatest benefits will be seen in the prevention of AKI in the experimental group. If these benefits reach a level of statistical significance and are considered clinically relev

—

Secondary

Measure	Time frame
Secondary end point(s): - n.a. -;Timepoint(s) of evaluation of this end point: - n.a. -	—

Countries

Australia, Austria, Belgium, Malaysia, Netherlands, Russian Federation, Singapore

Contacts

Public ContactContract Research Organisation

Aix Scientifics

eike@aix-scientifics.com+492414500 358

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026