Evaluation of the Effectiveness of Platelet-based and Microvesicle-based Assays to Predict Thrombotic and Bleeding Risk in Chronic Kidney Disease Patients With Acute Coronary Syndrome (INNOV CKD 1)

This study is part of the RHU INNOV-CKD, winner of the 2019 call for projects. Its aim is to develop two biomarker assays to assess the thrombotic and haemorrhagic risks in patients with stage 3A or more severe chronic kidney disease (CKD) treated with percutaneous coronary intervention (PCI) and antiplatelet therapy following an acute coronary syndrome (ACS). We believe that these tests will help to adapt antiplatelet therapy on an individual basis (in terms of intensity and duration of treatment) and thus reduce the risk of thrombotic and haemorrhagic events in this particularly fragile population. The first biomarker corresponds to an intra-platelet molecule, Rap1b in its active form (known as aRap1b). The second is the pro-antithrombotic balance of circulating endothelial microvesicles (patEMV), which reflects endothelial dysfunction. An automated method for measuring these biomarkers will be developed in partnership with the D.Stago and BioCytex industries during the course of the project.

Study Overview

• Status: Recruiting
• Conditions: Chronic Kidney Disease stage3
• Intervention / Treatment: Biological: Blood samples; Biological: Blood samples

• Study Type: Interventional
• Enrollment (Estimated): 850
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: LAURENT BONELLO; Phone Number: 0491968858; Email: laurent.bonello@ap-hm.fr

Study Locations

• France
  • Marseille, France, 13354
    • Recruiting
    • Assistance Publique Hopitaux de Marseille
    • Principal Investigator: BONELLO LAURENT
    • Contact: GIULIANI ALEXANDRA; Email: promotion.interne@ap-hm.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Man or woman ≥18 years old and <90
• If the subject is a woman, she must be on contraception or menopausal.

• 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) 56 or ST segment elevation ACS scheduled for primary PCI defined 57 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:

  1. ST-segment elevation ≥1 mm in two or more contiguous ECG leads
  2. New or presumably new left bundle branch block (LBBB).
  3. 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 (appendix X)
• Subject with CKD stage 3A or higher (estimated glomerular filtration rate (eGFR) ≤ 60 ml/min/1.73 m2 according to the CKD-EPI formula
• Because of the documented biological variability of eGRF levels, patients with a eGRF < 78 ml/min/1.73 m2 can be included in this study, based on previous blood test results and on the investigator's decision. The DFG level of 78 ml/min/1.73 m2 correspond to an increase of 30 % of a DFG of 60 ml/min/1.73 m2. Indeed, the literature estimated a DFG levels variability of 30 % 58-61.
• 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 diathesis;
• Subject not agreeing to participate.
• Subject with contraindication to clopidogrel, ticagrelor or to another anti platelet agent.
• Severe hepatic failure
• Ischemic Stroke within one month or a history of hemorrhagic stroke
• Platelet count<100 000
• Major surgery or trauma within 10 days
• Life expectancy <1 year
• Known significant bleeding risk according to the physician judgment
• Adults subject to a legal protection measure or unable to express their consent (persons under guardianship, curatorship or safeguard of justice)
• Persons deprived of their rights of liberty by judicial or administrative decision (persons in a situation of social fragility)
• Progressive cancer
• Systemic autoimmune disease
• Chronic viral or bacterial infections
• Diabetes requiring insulin therapy
• Constitutional haemorrhagic syndrome
• Organ transplantation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CKD patients	Biological: Blood samples; 12-24 hours after P2Y12 ADP receptor loading dose (LD); Biological: Blood samples; 1 month after Percutaneous Coronary Intervention (PCI)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
assessing the predictive value of high aRap1b expression	after antiplatelet loading dose in the occurrence of MACE	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
High Rap1b-GTP expression	after antiplatelet loading dose in the occurrence of MACE	1 month
High Rap1b-GTP expression	after antiplatelet loading dose in the occurrence of MACE	6 months
High Rap1b-GTP expression	after antiplatelet loading dose and after PCI in the occurrence of bleeding events	1 month
High Rap1b-GTP expression	after antiplatelet loading dose and after PCI in the occurrence of bleeding events	6 months
High Rap1b-GTP expression	after antiplatelet loading dose and after PCI in the occurrence of bleeding events	12 months
Low Rap1b-GTP expression	after antiplatelet loading dose and after PCI in the occurrence of MACE	1 month
Low Rap1b-GTP expression	after antiplatelet loading dose and after PCI in the occurrence of MACE	6 months
Low Rap1b-GTP expression	after antiplatelet loading dose and after PCI in the occurrence of MACE	12 months
Low Rap1b-GTP expression	after antiplatelet loading dose and after PCI in the occurrence of bleeding events	12 months
High MV procoagulant and profibrinolytic expressions	after antiplatelet loading dose and after PCI, in the occurrence of MACE	1 month
High MV procoagulant and profibrinolytic expressions	after antiplatelet loading dose and after PCI, in the occurrence of MACE	6 months
High MV procoagulant and profibrinolytic expressions	after antiplatelet loading dose and after PCI, in the occurrence of MACE	12 months
High MV procoagulant and profibrinolytic expressions	after antiplatelet loading dose and after PCI, in the occurrence of bleeding	6 months
High MV procoagulant and profibrinolytic expressions	after antiplatelet loading dose and after PCI, in the occurrence of bleeding	12 months

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille
• Investigators: Study Director: François CREMIEUX, Assistance Publique Hôpitaux Marseille

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: August 30, 2023
• First Submitted That Met QC Criteria: August 30, 2023
• First Posted (Actual): September 7, 2023

Study Record Updates

• Last Update Posted (Actual): October 27, 2023
• Last Update Submitted That Met QC Criteria: October 26, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Acute Coronary Syndrome
• Other Study ID Numbers: RCAPHM23_0073 - INNOV-CKD1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No