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

Sponsor

Assistance Publique Hopitaux De Marseille (Other)

Overall Status

Recruiting

CT.gov ID

NCT03357874

Collaborator

(none)

514

Enrollment

Location

Arms

57.1

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Coronary Syndrome	Drug: Clopidogrel Drug: Ticagrelor	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

514 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 28, 2018

Anticipated Primary Completion Date :

Jan 1, 2023

Anticipated Study Completion Date :

Aug 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Clopidogrel group	Drug: Clopidogrel 600 mg loading dose of clopidogrel as pretreatment followed by 75 mg daily for 12 months (52 weeks).
Experimental: Ticagrelor group	Drug: Ticagrelor patients will receive a 180 mg loading dose as pretreatment of PCI followed by 90 mg bi-daily for 12 months (52 weeks).

Arm

Intervention/Treatment

Experimental: Clopidogrel group

Drug: Clopidogrel

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

Experimental: Ticagrelor group

Drug: Ticagrelor

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

Outcome Measures

Primary Outcome Measures

the rate of major adverse cardiovascular events [12 MONTHS]

Secondary Outcome Measures

the rate of bleedings [1 MONTH AND 12MONTHS]
using the Bleeding Academic Research Consortium classification ≥3 defined at discharge
the rate of myocardial infarction at discharge [1 MONTH AND 12MONTHS]
the rate of cardiovascular death at discharge [1MONTH AND 12 MONTHS]
the rate of urgent revascularization at discharge [1MONTH AND 12 MONTHS]
the rate of all-cause death at discharge [1MONTH AND 12 MONTHS]
the rate of hospital re-admission [1MONTH AND 12 MONTHS]
the rate of probable and definite stent thrombosis (ARC definition) at discharge [1MONTH AND 12 MONTHS]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.