Prevention of Acute Kidney Injury in Patients With NSTEMI

Study Overview
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Brief Summary
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A randomized, double-blind, placebo-controlled, multi-center, phase 2 clinical study in patients with NSTEMI undergoing urgent coronary angiography. Approximately 220 patients with CKD and acute NSTEMI, who are scheduled for an urgent coronary angiography (within 72 hours after admission and/or diagnosis of NSTEMI).

Detailed Description
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Approximately 220 patients with chronic kidney disease (CKD) and acute NSTEMI, who are scheduled for an urgent coronary angiography (within 72 hours after admission and/or diagnosis of NSTEMI) will be screened for the study. Only patients with acute NSTEMI presumed to be a spontaneous myocardial infarction, related to atherosclerotic plaque rupture, ulceration, fissuring, erosion, or dissection (i.e. type 1) are eligible. Written informed consent will be obtained before urgent coronary angiography. Patients with NSTEMI will typically undergo coronary angiography within 72 hours after admission and/or diagnosis of NSTEMI. It is estimated that 70% of these patients will have PCI. Randomization will continue until the 160th patient has had a PCI.

Official Title
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Conestat Alfa (a Recombinant Human C1 Esterase Inhibitor) for the Prevention of Acute Kidney Injury After Non-ST Elevation Myocardial Infarction: a Randomized, Double-blind, Placebo-controlled, Multicenter, Phase 2, Dose-finding Study

Conditions
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Non-ST Elevation Myocardial Infarction (NSTEMI)

Intervention / Treatment
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* Drug: conestat alfa or placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed Consent as documented by a signature and date of the patient Age 18-85 years Acute NSTEMI as anticipated to be type 1 (expert opinion by the cardiologist before coronary angiography) and scheduled for urgent coronary angiography Documented kidney disease existing for ≥3 months OR Two estimated glomerular filtration rate (eGFR) measurements of <60ml/min/1.73m2 as calculated by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) study equation and at least 6 hours apart OR eGFR of <50 mL/min//1.73m2 as calculated by using the CKD-EPI study equation at presentation At least one of the following risk factors for AKI: diabetes mellitus, age >60 years, established cardiovascular disease, heart failure with reduced ejection fraction, anemia Exclusion Criteria: Contraindications to the class of drugs under study (C1 esterase inhibitors), e.g. known hypersensitivity or allergy to class of drugs or the IMP History or suspicion of allergy to rabbits Women who are pregnant or breast feeding ST elevation myocardial infarction or unstable angina Cardiogenic shock requiring mechanical support Non-cardiac comorbidity with expected survival <6 months Acute urinary tract infection (e.g. cystitis, pyelonephritis). Liver cirrhosis (any Child-Pugh score) Dialysis or eGFR <20 and >59mL/min/1.73 m2 at baseline (d0) Incapacity or inability to provide informed consent Participation in another study with investigational drug within 30 days preceding, and during the present study Previous enrolment into the current study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blind, placebo-controlled, multicenter, phase 2, dose-finding.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Conestat alfa 50 U/kg - Placebo<br>50 U/kg conestat alfa pre-angiography and placebo 3 hours after the first dose | Drug: conestat alfa or placebo<br>* Conestat alfa will be dosed by body weight at 50 U/kg (maximum 4200 U) or 100 U/kg (maximum 8400 U). Placebo will consist of normal saline (NaCl 0.9%). The interventions will be given to the patients by IV-line.<br>* Other names: Ruconest;|
| Active Comparator: Conestat alfa 50 U/kg - Conestat alfa 50 U/kg<br>50 U/kg conestat alfa pre-angiography and 3 hours after the first dose | Drug: conestat alfa or placebo<br>* Conestat alfa will be dosed by body weight at 50 U/kg (maximum 4200 U) or 100 U/kg (maximum 8400 U). Placebo will consist of normal saline (NaCl 0.9%). The interventions will be given to the patients by IV-line.<br>* Other names: Ruconest;|
| Active Comparator: Conestat alfa 100 U/kg - Conestat alfa 50 U/kg<br>100 U/kg conestat alfa pre-angiography and 50 U/kg conestat alfa 3 hours after the first dose | Drug: conestat alfa or placebo<br>* Conestat alfa will be dosed by body weight at 50 U/kg (maximum 4200 U) or 100 U/kg (maximum 8400 U). Placebo will consist of normal saline (NaCl 0.9%). The interventions will be given to the patients by IV-line.<br>* Other names: Ruconest;|
| Placebo Comparator: Placebo - Placebo<br>Placebo pre-angiography and 3 hours after the first dose | Drug: conestat alfa or placebo<br>* Conestat alfa will be dosed by body weight at 50 U/kg (maximum 4200 U) or 100 U/kg (maximum 8400 U). Placebo will consist of normal saline (NaCl 0.9%). The interventions will be given to the patients by IV-line.<br>* Other names: Ruconest;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary NGAL | Evaluation of the peak change of urinary NGAL, an established biomarker of AKI, within 24 hours after PCI | 24 hours after PCI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary NGAL | The peak change of urinary NGAL within 24 hours after angiography for the total group including PCI and non-PCI patients | within 24 hours after angiography | 
| Serum creatinine | The incidence of acute kidney injury (AKI) as defined by a serum creatinine change of ≥26.5 µmol/L or a serum creatinine change of ≥1.5 times baseline within 72 hours after angiography. | within 72 hours after angiography | 
| Serum cystatin C | The incidence of a serum cystatin C change of ≥10% 24 hours after angiography. | 24 hours after angiography | 
| Troponin T | The change of troponin T within 72 hours (area under the curve, AUC0-72) after angiography | within 72 hours after angiography | 
| Troponin T | The peak change of troponin | measured once at 72 hours after angiography | 
| Creatine kinase | The peak change of creatine kinase | measured once at 72 hours after angiography | 
| N-terminal pro-brain natriuretic peptide | N-terminal pro-brain natriuretic peptide (NT-proBNP) measured once at 72 hours after angiography | at 72 hours after angiography |