Bedside Genetic or Pharmacodynamic Testing to Prevent Periprocedural Myonecrosis During PCI (ONSIDE TEST) (ONSIDE TEST)

Optimal P2Y12-receptor treatmeNt Guided by bedSIDe Genetic or Pharmacodynamic TESTing to Prevent Periprocedural Myonecrosis During Elective Percutaneous Coronary Intervention.

Patients undergoing percutaneous coronary intervention with a residual high platelet reactivity despite oral clopidogrel are at increased risk of ischaemic complications. The strategies to overcome the issue consist of switch to a more potent antiplatelet medications including prasugrel or ticagrelor. Economic constrains of many countries still do not allow wide reimbursement of newer antiplatelet agents. Therefore a strategy to personalise treatment according to genotype and phenotype characteristics of the patient may provide an attractive solution combining high clinical efficacy with low budget impact.

Study Overview

• Status: Unknown
• Conditions: Stable Angina
• Intervention / Treatment: Device: Genotyping; Device: Phenotyping

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 3

Contacts and Locations

Study Locations

• Hungary
  • Balatonfüred, Hungary, 8230
    • Active, not recruiting
    • Heart Center Balatonfüred
• Poland
  • Warsaw, Poland, 02-097
    • Recruiting
    • 1st Department of Cardiology, Medical University of Warsaw
    • Principal Investigator: Lukasz Koltowski, MD
    • Sub-Investigator: Mariusz Tomaniak, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age 18-75
• elective PCI

Exclusion Criteria:

• acute coronary syndrome (troponin > 1 x ULN),
• administration of glycoprotein IIb/IIIa inhibitors,
• chronic total occlusion,
• lesions with extensive calcifications requiring rotational atherectomy,
• platelet count <70 000 /µl
• high bleeding risk,
• coronary bypass surgery in the previous 3 months,
• severe chronic renal failure (eGFR < 30 mL/min)
• requirement for warfarin, dabigatran, apixaban, rivaroxaban
• history of stroke or TIA,
• weight < 60 kg
• known bleeding diathesis,
• hematocrit of < 30% or >52%
• pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Genotyping Arm; Rapid genotyping to select optimal P2Y12-inhibitor for PCI.	Device: Genotyping; Patients harboring CYP2C19 *2 alleles receive 60 mg prasugrel for PCI, while non-carriers receive 600 mg clopidogrel if not pretreated with clopidogrel.; Other Names: Spartan rapid genotyping device to screen CYP2C19 *2 carriage in patients in the Genotyping Arm.
Experimental: Phenotying Arm; The use of platelet function testing to select the optimal P2Y12-inhibitor for PCI.	Device: Phenotyping; Patients having high on-treatment platelet reactivity (HPR: greater than 208 PRU) receive 60 mg prasugrel loading dose (LD), others continue clopidogrel for PCI.; Other Names: VerifyNow P2Y12 assay to test the response to clopidogrel.
No Intervention: Conventional Arm; Regular approach for performing elective PCI.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of periprocedural myocardial injury within 24 h after PCI	Post-procedural troponin value increase exceeding the 99th percentile upper reference limit (URL) within 24 hours after PCI	Within 24 hours after Percutaneous Coronary Intervention (PCI)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients having periprocedural myocardial infarction (MI)	Periprocedural MI is defined as a CK-MB elevation greater than 3x of the upper limit of norm (ULN) within 24 hours of elective PCI.	Within 24 hours or PCI

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak troponin elevation	The level of peak troponin-I elevation during 24 hours of elective PCI	Within 24 hours of PCI
Proportion of patients with peri-procedural MI	The rate of peri-procedural MI defined as a peak troponin-I value greater than 5x the ULN within 24 hours.	Within 24 hours of PCI
BARC type 3 and 5 bleeding	BARC-defined type 3 (clinical, laboratory, and/or imaging evidence of bleeding, with healthcare provider responses) and type 5 (fatal) bleeds happening within 7 days of PCI.	Within 1 week of PCI
Death, MI, stent thrombosis (ST) or urgent repeat revascularization	The rate of cardiac death, myocardial infarction, definite or probable stent thrombosis or urgent repeat revascularization within 30 days of elective PCI.	30 days after PCI

Collaborators and Investigators

• Sponsor: Medical University of Warsaw
• Collaborators: University of Pecs; Polish Cardiac Society

Publications and helpful links

General Publications

• Koltowski L, Aradi D, Huczek Z, Tomaniak M, Sibbing D, Filipiak KJ, Kochman J, Balsam P, Opolski G. Study design and rationale for Optimal aNtiplatelet pharmacotherapy guided by bedSIDE genetic or functional TESTing in elective percutaneous coronary intervention patients (ONSIDE TEST): a prospective, open-label, randomised parallel-group multicentre trial (NCT01930773). Kardiol Pol. 2016;74(4):372-9. doi: 10.5603/KP.a2015.0172. Epub 2015 Sep 14.

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Anticipated): March 1, 2019
• Study Completion (Anticipated): September 1, 2019

Study Registration Dates

• First Submitted: August 25, 2013
• First Submitted That Met QC Criteria: August 25, 2013
• First Posted (Estimate): August 29, 2013

Study Record Updates

• Last Update Posted (Actual): December 24, 2018
• Last Update Submitted That Met QC Criteria: December 21, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: prasugrel; clopidogrel; genotyping; platelet function testing; peri-procedural MI
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Chest Pain; Angina Pectoris; Angina, Stable; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel
• Other Study ID Numbers: ONSIDE TEST; Klub 30, 2012 (Other Identifier: Polish Cardiac Society)

Plan for Individual participant data (IPD)

Study Data/Documents

1. Study Protocol
   Information comments:

   Study design and rationale for Optimal aNtiplatelet pharmacotherapy guided by bedSIDE genetic or functional TESTing in elective percutaneous coronary intervention patients (ONSIDE TEST): a prospective, open-label, randomised parallel-group multicentre trial (NCT01930773).

   Kołtowski Ł, Aradi D, Huczek Z, Tomaniak M, Sibbing D, Filipiak KJ, Kochman J, Balsam P, Opolski G.

   Kardiol Pol. 2016;74(4):372-9. doi: 10.5603/KP.a2015.0172.

2. Clinical Study Report
   Information comments:

   Optimal aNtiplatelet pharmacotherapy guided by bedSIDE genetic or functional TESTing in elective PCI patients: A pilot study: ONSIDE TEST pilot.

   Koltowski L, Tomaniak M, Aradi D, Huczek Z, Filipiak KJ, Kochman J, Gajda S, Balsam P, Opolski G.

   Cardiol J. 2017 Mar 10. doi: 10.5603/CJ.a2017.0026. [Epub ahead of print]