Prevention of Acute Kidney Injury in Patients With NSTEMI

Non-ST Elevation Myocardial Infarction (NSTEMI) Clinical Trial

— AKI  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04912141
• Other study ID #: C1 5201
• Status: Terminated
• Phase: Phase 2
• Start date: April 21, 2021
• Est. completion date: April 28, 2023

Study information

• Verified date: December 2023
• Source: Pharming Technologies B.V.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 29
• Est. completion date: April 28, 2023
• Est. primary completion date: April 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Kidney Injury
• Infarction
• Myocardial Infarction
• Non-ST Elevated Myocardial Infarction
• Non-ST Elevation Myocardial Infarction (NSTEMI)

Intervention

Drug:
• conestat alfa or placebo
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.

Locations

Country	Name	City	State
Switzerland	University Hospital Basel	Basel
Switzerland	Inselspital Bern	Bern
Switzerland	University Hospital Geneva	Geneva
Switzerland	Fondazione Istituto Cardiocentro Ticino	Lugano

Sponsors (1)

Lead Sponsor	Collaborator
Pharming Technologies B.V.

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Serum cystatin C	The incidence of a serum cystatin C change of =10% 24 hours after angiography.	24 hours after angiography
Secondary	Troponin T	The change of troponin T within 72 hours (area under the curve, AUC0-72) after angiography	within 72 hours after angiography
Secondary	Troponin T	The peak change of troponin	measured once at 72 hours after angiography
Secondary	Creatine kinase	The peak change of creatine kinase	measured once at 72 hours after angiography
Secondary	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