Non-ST Elevation Myocardial Infarction (NSTEMI)
Conditions
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.
Interventions
DRUGconestat 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.
Sponsors
Pharming Technologies B.V.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized, double-blind, placebo-controlled, multicenter, phase 2, dose-finding.
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Serum cystatin C | 24 hours after angiography | The incidence of a serum cystatin C change of ≥10% 24 hours after angiography. |
| 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 |
| 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 |
| Troponin T | within 72 hours after angiography | The change of troponin T within 72 hours (area under the curve, AUC0-72) after angiography |
Countries
Switzerland
Outcome results
None listed