Prevention of Acute Kidney Injury in Patients With NSTEMI (AKI)

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

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).

Study Overview

• Status: Terminated
• Conditions: Non-ST Elevation Myocardial Infarction (NSTEMI)
• Intervention / Treatment: Drug: conestat alfa or placebo

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 Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • University Hospital Basel
  • Bern, Switzerland, 3010
    • Inselspital Bern
  • Geneva, Switzerland, 1205
    • University Hospital Geneva
  • Lugano, Switzerland, 6900
    • Fondazione Istituto Cardiocentro Ticino

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Conestat alfa 50 U/kg - Placebo; 50 U/kg conestat alfa pre-angiography and placebo 3 hours after the first dose	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.; Other Names: Ruconest
Active Comparator: Conestat alfa 50 U/kg - Conestat alfa 50 U/kg; 50 U/kg conestat alfa pre-angiography and 3 hours after the first dose	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.; Other Names: Ruconest
Active Comparator: Conestat alfa 100 U/kg - Conestat alfa 50 U/kg; 100 U/kg conestat alfa pre-angiography and 50 U/kg conestat alfa 3 hours after the first dose	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.; Other Names: Ruconest
Placebo Comparator: Placebo - Placebo; Placebo pre-angiography and 3 hours after the first dose	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.; Other Names: Ruconest

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pharming Technologies B.V.
• Investigators: Study Director: Anurag Relan, MD, Pharming Technologies BV

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2021
• Primary Completion (Actual): April 28, 2023
• Study Completion (Actual): April 28, 2023

Study Registration Dates

• First Submitted: May 21, 2021
• First Submitted That Met QC Criteria: May 27, 2021
• First Posted (Actual): June 3, 2021

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Kidney Diseases; Urologic Diseases; Renal Insufficiency; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Myocardial Infarction; Infarction; Acute Kidney Injury; Non-ST Elevated Myocardial Infarction; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Complement C1 Inhibitor Protein
• Other Study ID Numbers: C1 5201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No