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

Primary Purpose

Non-ST Elevation Myocardial Infarction (NSTEMI)

Status

Recruiting

Phase

Phase 2

Locations

Switzerland

Study Type

Interventional

Intervention

conestat alfa or placebo

About this trial

This is an interventional prevention trial for Non-ST Elevation Myocardial Infarction (NSTEMI)

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University Hospital BaselRecruiting
Inselspital BernRecruiting
University Hospital GenevaRecruiting
Fondazione Istituto Cardiocentro TicinoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Active Comparator

Placebo Comparator

Arm Label

Conestat alfa 50 U/kg - Placebo

Conestat alfa 50 U/kg - Conestat alfa 50 U/kg

Conestat alfa 100 U/kg - Conestat alfa 50 U/kg

Placebo - Placebo

Arm Description

50 U/kg conestat alfa pre-angiography and placebo 3 hours after the first dose

50 U/kg conestat alfa pre-angiography and 3 hours after the first dose

100 U/kg conestat alfa pre-angiography and 50 U/kg conestat alfa 3 hours after the first dose

Placebo pre-angiography and 3 hours after the first dose

Outcomes

Primary Outcome Measures

Urinary NGAL

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

Secondary Outcome Measures

Urinary NGAL

The peak change of urinary NGAL within 24 hours after angiography for the total group including PCI and non-PCI patients

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.

Serum cystatin C

The incidence of a serum cystatin C change of ≥10% 24 hours after angiography.

Troponin T

The change of troponin T within 72 hours (area under the curve, AUC0-72) after angiography

Troponin T

The peak change of troponin

Creatine kinase

The peak change of creatine kinase

N-terminal pro-brain natriuretic peptide

N-terminal pro-brain natriuretic peptide (NT-proBNP) measured once at 72 hours after angiography

Full Information

NCT ID

NCT04912141

First Posted

May 21, 2021

Last Updated

May 27, 2021

Sponsor

Pharming Technologies B.V.

1. Study Identification

Unique Protocol Identification Number

NCT04912141

Brief Title

Prevention of Acute Kidney Injury in Patients With NSTEMI

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Recruiting

Study Start Date

April 21, 2021 (Actual)

Primary Completion Date

December 2022 (Anticipated)

Study Completion Date

December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Pharming Technologies B.V.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-ST Elevation Myocardial Infarction (NSTEMI)

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

Randomized, double-blind, placebo-controlled, multicenter, phase 2, dose-finding.

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

220 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Conestat alfa 50 U/kg - Placebo

Arm Type

Placebo Comparator

Arm Description

50 U/kg conestat alfa pre-angiography and placebo 3 hours after the first dose

Arm Title

Conestat alfa 50 U/kg - Conestat alfa 50 U/kg

Arm Type

Active Comparator

Arm Description

50 U/kg conestat alfa pre-angiography and 3 hours after the first dose

Arm Title

Conestat alfa 100 U/kg - Conestat alfa 50 U/kg

Arm Type

Active Comparator

Arm Description

100 U/kg conestat alfa pre-angiography and 50 U/kg conestat alfa 3 hours after the first dose

Arm Title

Placebo - Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo pre-angiography and 3 hours after the first dose

Intervention Type

Drug

Intervention Name(s)

conestat alfa or placebo

Other Intervention Name(s)

Ruconest

Intervention Description

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.

Primary Outcome Measure Information:

Title

Urinary NGAL

Description

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

Time Frame

24 hours after PCI

Secondary Outcome Measure Information:

Title

Urinary NGAL

Description

The peak change of urinary NGAL within 24 hours after angiography for the total group including PCI and non-PCI patients

Time Frame

within 24 hours after angiography

Title

Serum creatinine

Description

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.

Time Frame

within 72 hours after angiography

Title

Serum cystatin C

Description

The incidence of a serum cystatin C change of ≥10% 24 hours after angiography.

Time Frame

24 hours after angiography

Title

Troponin T

Description

The change of troponin T within 72 hours (area under the curve, AUC0-72) after angiography

Time Frame

within 72 hours after angiography

Title

Troponin T

Description

The peak change of troponin

Time Frame

measured once at 72 hours after angiography

Title

Creatine kinase

Description

The peak change of creatine kinase

Time Frame

measured once at 72 hours after angiography

Title

N-terminal pro-brain natriuretic peptide

Description

N-terminal pro-brain natriuretic peptide (NT-proBNP) measured once at 72 hours after angiography

Time Frame

at 72 hours after angiography

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Jurgen Schaale, MD

Phone

+31715247400

j.schaale@pharming.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Anurag Relan, MD

Organizational Affiliation

Pharming Technologies BV

Official's Role

Study Director

Facility Information:

Facility Name

University Hospital Basel

City

Basel

ZIP/Postal Code

4031

Country

Switzerland

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Michael Osthoff, MD

Facility Name

Inselspital Bern

City

Bern

ZIP/Postal Code

3010

Country

Switzerland

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Lorenz Raber, MD

Facility Name

University Hospital Geneva

City

Geneva

ZIP/Postal Code

1205

Country

Switzerland

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Juan Fernando Iglesias, MD

Facility Name

Fondazione Istituto Cardiocentro Ticino

City

Lugano

ZIP/Postal Code

6900

Country

Switzerland

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Marco Moccetti, MD

12. IPD Sharing Statement

Plan to Share IPD

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Prevention of Acute Kidney Injury in Patients With NSTEMI

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