Prevention of Acute Kidney Injury in Patients With NSTEMI

Phase 2

Terminated

• Conditions: Non-ST Elevation Myocardial Infarction (NSTEMI)
• Interventions: Drug: conestat alfa or placebo

• Registration Number: NCT04912141
• Lead Sponsor: Pharming Technologies B.V.

Brief Summary

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

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.

Study Timeline

• Study Start: 2021-04-21
• Study First Submitted: 2021-05-21
• Study First Submitted QC: 2021-05-27
• Study First Posted: 2021-06-03
• Primary Completion: 2023-04-28
• Study Completion: 2023-04-28
• Status Verified: 2023-12
• Last Update Submitted: 2024-04-01
• Last Update Posted: 2024-04-03

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

1. Informed Consent as documented by a signature and date of the patient
2. Age 18-85 years
3. Acute NSTEMI as anticipated to be type 1 (expert opinion by the cardiologist before coronary angiography) and scheduled for urgent coronary angiography
4. 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
5. 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

1. Contraindications to the class of drugs under study (C1 esterase inhibitors), e.g. known hypersensitivity or allergy to class of drugs or the IMP
2. History or suspicion of allergy to rabbits
3. Women who are pregnant or breast feeding
4. ST elevation myocardial infarction or unstable angina
5. Cardiogenic shock requiring mechanical support
6. Non-cardiac comorbidity with expected survival <6 months
7. Acute urinary tract infection (e.g. cystitis, pyelonephritis).
8. Liver cirrhosis (any Child-Pugh score)
9. Dialysis or eGFR <20 and >59mL/min/1.73 m2 at baseline (d0)
10. Incapacity or inability to provide informed consent
11. Participation in another study with investigational drug within 30 days preceding, and during the present study
12. Previous enrolment into the current study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Conestat alfa 50 U/kg - Placebo	conestat alfa or placebo	50 U/kg conestat alfa pre-angiography and placebo 3 hours after the first dose
Conestat alfa 50 U/kg - Conestat alfa 50 U/kg	conestat alfa or placebo	50 U/kg conestat alfa pre-angiography and 3 hours after the first dose
Conestat alfa 100 U/kg - Conestat alfa 50 U/kg	conestat alfa or placebo	100 U/kg conestat alfa pre-angiography and 50 U/kg conestat alfa 3 hours after the first dose
Placebo - Placebo	conestat alfa or placebo	Placebo pre-angiography and 3 hours after the first dose

Primary Outcome Measures

Name	Time	Method
Urinary NGAL	24 hours after PCI	Evaluation of the peak change of urinary NGAL, an established biomarker of AKI, within 24 hours after PCI

Secondary Outcome Measures

Name	Time	Method
Troponin T	measured once at 72 hours after angiography	The peak change of troponin
Urinary NGAL	within 24 hours after angiography	The peak change of urinary NGAL within 24 hours after angiography for the total group including PCI and non-PCI patients
Creatine kinase	measured once at 72 hours after angiography	The peak change of creatine kinase
Serum creatinine	within 72 hours after angiography	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.
N-terminal pro-brain natriuretic peptide	at 72 hours after angiography	N-terminal pro-brain natriuretic peptide (NT-proBNP) measured once at 72 hours after angiography
Serum cystatin C	24 hours after angiography	The incidence of a serum cystatin C change of ≥10% 24 hours after angiography.

Trial Locations

Locations (4)

Fondazione Istituto Cardiocentro Ticino; 🇨🇭 Lugano, Switzerland

University Hospital Geneva; 🇨🇭 Geneva, Switzerland

University Hospital Basel; 🇨🇭 Basel, Switzerland

Inselspital Bern; 🇨🇭 Bern, Switzerland