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TicagRelor Or Clopidogrel in Severe and Terminal Chronic Kidney Disease Patients Undergoing PERcutaneous Coronary Intervention for an Acute Coronary Syndrome. (TROUPER)

Primary Purpose

Acute Coronary Syndrome

Status

Unknown status

Phase

Phase 3

Locations

France

Study Type

Interventional

Intervention

Clopidogrel

Ticagrelor

About this trial

This is an interventional treatment trial for Acute Coronary Syndrome

Eligibility Criteria

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

Inclusion Criteria:

- Must not be of child-bearing potential (1 year post-menopausal, contraceptive or surgically sterile).

non-ST-segment elevation ACS defined by the presence of at least 2 of the following criteria: (1) symptoms of myocardial ischemia, (2) electrocardiographic ST-segment abnormalities (depression or transient elevation of at least 0.1 mV) or T-wave inversion in at least in 2 contiguous leads, or (3) an elevated cardiac troponin value (above the upper limit of normal) (2) or ST segment elevation ACS scheduled for primary PCI defined (22)as a history of chest discomfort or ischemic symptoms of >20 minutes duration at rest ≤14 days prior to entry into the study with one of the following present on at least one ECG prior to randomization:

ST-segment elevation ≥1 mm in two or more contiguous ECG leads.
New or presumably new left bundle branch block (LBBB).
ST-segment depression ≥1 mm in two anterior precordial leads (V1 through V4) with clinical history and evidence suggestive of true posterior infarction
- Subject intended for an invasive strategy if NSTE-ACS or primary PCI if STE-ACS according to guidelines (annexe 1)
- Subject CKD stage 4 and 5 (estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2 by (MDRD formula) or undergoing chronic dialysis
- Must be enrolled at a cardiac catheterization laboratory hospital or at a hospital/ambulance service affiliated with a cardiac catheterization laboratory hospital.
- Subject affiliated to or beneficiary of a social security system.
- Subject having signed written informed consent.

Exclusion Criteria:

Minors, pregnant or breast-feeding women;
Subject under chronic anticoagulant
Subject with thrombolytic therapy during the preceding 24 hours;
Subject with bleeding ;
Subject participating in another research protocol;
Subject not agreeing to participate.
Subject with contraindication to clopidogrel or ticagrelor
Severe hepatic failure
Ischemic Stroke within one month or a history of hemorrhagic stroke
Bradycardia
Platelet count<100 000
Major surgery or trauma within 10 days
Life expectancy <1 year
Known significant bleeding risk according to the physician judgment

Sites / Locations

APHMRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Clopidogrel group

Ticagrelor group

Arm Description

Outcomes

Primary Outcome Measures

the rate of major adverse cardiovascular events

Secondary Outcome Measures

the rate of bleedings

using the Bleeding Academic Research Consortium classification ≥3 defined at discharge

the rate of myocardial infarction at discharge

the rate of cardiovascular death at discharge

the rate of urgent revascularization at discharge

the rate of all-cause death at discharge

the rate of hospital re-admission

the rate of probable and definite stent thrombosis (ARC definition) at discharge

Full Information

NCT ID

NCT03357874

First Posted

November 14, 2017

Last Updated

January 18, 2021

Sponsor

Assistance Publique Hopitaux De Marseille

1. Study Identification

Unique Protocol Identification Number

NCT03357874

Brief Title

TicagRelor Or Clopidogrel in Severe and Terminal Chronic Kidney Disease Patients Undergoing PERcutaneous Coronary Intervention for an Acute Coronary Syndrome.

Acronym

TROUPER

Official Title

TicagRelor Or Clopidogrel in Severe and Terminal Chronic Kidney Disease Patients Undergoing PERcutaneous Coronary Intervention for an Acute Coronary Syndrome.

Study Type

Interventional

2. Study Status

Record Verification Date

January 2021

Overall Recruitment Status

Unknown status

Study Start Date

October 28, 2018 (Actual)

Primary Completion Date

January 2023 (Anticipated)

Study Completion Date

August 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Assistance Publique Hopitaux De Marseille

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

Ticagrelor is a potent and fast-acting P2Y12-ADP receptor antagonist recommended as first-line agent in ACS (2). This drug was associated with a 20% relative reduction in the rate of MACE in ACS patients undergoing PCI compared to clopidogrel. This benefit came without any increase in major bleedings compared to clopidogrel (6). In the PLATO trial, a limited number of kidney failure patients were included (21%) and patients with terminal CKD were excluded. A sub-group analysis focused on CKD patients was performed. Only 214 patients with CKD below stage 4 (creatinine clearance <30 ml/min) were included (7). No patient with terminal CKD or undergoing chronic hemodialysis was included. Of importance, kidney function impairment is frequent and affects up-to 40 % of ACS patients. In addition, CKD is a powerful independent predictor of ischemic complications during ACS (8-9).Indeed, CKD patients have a very high risk of MACE following ACS with an odd ratio between 2 and 3 compared to patients with normal kidney function and event rates above 40% at one year follow-up (8-13). Of importance these patients more often have high on-clopidogrel platelet reactivity which was strongly associated with a worse clinical outcome (3,14-16). In CKD patients HTPR was associated with death after PCI (15). Accordingly ticagrelor which overcomes these limitations of clopidogrel could be associated with a major clinical benefit in severe or terminal CKD patients. Most of ticagrelor and is active metabolites are excreted through the feces. Preclinical data suggested that renal impairment had little effect on systemic exposure to the drug(EMEA/H/C/1241 (28)). Recent pharmacodynamic and kinetic studies confirmed these preclinical data on the safety of ticagrelor in severe and end-stage CKD (17-19). Therefore based on the rational above and to the lack of relevant clinical data, the optimal P2Y12-ADP receptor antagonist for patients with stage 4 and 5 and patients undergoing chronic dialysis remains undetermined in ACS treated with PCI. We aimed to compare the clinical efficacy ticagrelor and clopidogrel in patients with stage 4 and 5 or on chronic hemodialysis undergoing PCI for ACS.

6. Conditions and Keywords

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

Acute Coronary Syndrome

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

514 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Clopidogrel group

Arm Type

Experimental

Arm Title

Ticagrelor group

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Clopidogrel

Intervention Description

600 mg loading dose of clopidogrel as pretreatment followed by 75 mg daily for 12 months (52 weeks).

Intervention Type

Drug

Intervention Name(s)

Ticagrelor

Intervention Description

patients will receive a 180 mg loading dose as pretreatment of PCI followed by 90 mg bi-daily for 12 months (52 weeks).

Primary Outcome Measure Information:

Title

the rate of major adverse cardiovascular events

Time Frame

12 MONTHS

Secondary Outcome Measure Information:

Title

the rate of bleedings

Description

using the Bleeding Academic Research Consortium classification ≥3 defined at discharge

Time Frame

1 MONTH AND 12MONTHS

Title

the rate of myocardial infarction at discharge

Time Frame

1 MONTH AND 12MONTHS

Title

the rate of cardiovascular death at discharge

Time Frame

1MONTH AND 12 MONTHS

Title

the rate of urgent revascularization at discharge

Time Frame

1MONTH AND 12 MONTHS

Title

the rate of all-cause death at discharge

Time Frame

1MONTH AND 12 MONTHS

Title

the rate of hospital re-admission

Time Frame

1MONTH AND 12 MONTHS

Title

the rate of probable and definite stent thrombosis (ARC definition) at discharge

Time Frame

1MONTH AND 12 MONTHS

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: - Must not be of child-bearing potential (1 year post-menopausal, contraceptive or surgically sterile). non-ST-segment elevation ACS defined by the presence of at least 2 of the following criteria: (1) symptoms of myocardial ischemia, (2) electrocardiographic ST-segment abnormalities (depression or transient elevation of at least 0.1 mV) or T-wave inversion in at least in 2 contiguous leads, or (3) an elevated cardiac troponin value (above the upper limit of normal) (2) or ST segment elevation ACS scheduled for primary PCI defined (22)as a history of chest discomfort or ischemic symptoms of >20 minutes duration at rest ≤14 days prior to entry into the study with one of the following present on at least one ECG prior to randomization: ST-segment elevation ≥1 mm in two or more contiguous ECG leads. New or presumably new left bundle branch block (LBBB). ST-segment depression ≥1 mm in two anterior precordial leads (V1 through V4) with clinical history and evidence suggestive of true posterior infarction Subject intended for an invasive strategy if NSTE-ACS or primary PCI if STE-ACS according to guidelines (annexe 1) Subject CKD stage 4 and 5 (estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2 by (MDRD formula) or undergoing chronic dialysis Must be enrolled at a cardiac catheterization laboratory hospital or at a hospital/ambulance service affiliated with a cardiac catheterization laboratory hospital. Subject affiliated to or beneficiary of a social security system. Subject having signed written informed consent. Exclusion Criteria: Minors, pregnant or breast-feeding women; Subject under chronic anticoagulant Subject with thrombolytic therapy during the preceding 24 hours; Subject with bleeding ; Subject participating in another research protocol; Subject not agreeing to participate. Subject with contraindication to clopidogrel or ticagrelor Severe hepatic failure Ischemic Stroke within one month or a history of hemorrhagic stroke Bradycardia Platelet count<100 000 Major surgery or trauma within 10 days Life expectancy <1 year Known significant bleeding risk according to the physician judgment

Central Contact Person:

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

LAURENT BONELLO

Phone

33(0)4 91 96 86 83

laurent.bonello@ap-hm.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

jean -olivier ARNAUD

Organizational Affiliation

AP HM

Official's Role

Study Director

Facility Information:

Facility Name

APHM

City

Marseille

ZIP/Postal Code

13354

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

LAURENT BONELLO

laurent.bonello@ap-hm.fr

12. IPD Sharing Statement

Citations:

PubMed Identifier

35224730

Citation

Natale P, Palmer SC, Saglimbene VM, Ruospo M, Razavian M, Craig JC, Jardine MJ, Webster AC, Strippoli GF. Antiplatelet agents for chronic kidney disease. Cochrane Database Syst Rev. 2022 Feb 28;2(2):CD008834. doi: 10.1002/14651858.CD008834.pub4.

Results Reference

derived

PubMed Identifier

32473355

Citation

Laine M, Lemesle G, Burtey S, Cayla G, Range G, Quaino G, Canault M, Pankert M, Paganelli F, Puymirat E, Bonello L. TicagRelor Or Clopidogrel in severe or terminal chronic kidney patients Undergoing PERcutaneous coronary intervention for acute coronary syndrome: The TROUPER trial. Am Heart J. 2020 Jul;225:19-26. doi: 10.1016/j.ahj.2020.04.013. Epub 2020 Apr 30.

Results Reference

derived

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TicagRelor Or Clopidogrel in Severe and Terminal Chronic Kidney Disease Patients Undergoing PERcutaneous Coronary Intervention for an Acute Coronary Syndrome.

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