The INtegrilin Plus STenting to Avoid Myocardial Necrosis Trial (INSTANT)

Sponsor

University of Turin, Italy (Other)

Overall Status

Terminated

CT.gov ID

NCT01454440

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

3.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Patients with stable coronary artery disease, undergoing PCI by means of implantation of >33 mm of DES, will be randomized single-blinded to eptifibatide plus unfractioned heparin according to the ESPRIT protocol vs placebo plus unfractioned heparin.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease	Drug: Eptifibatide	Phase 4

Detailed Description

BACKGROUND: Despite the availability of several potent antithrombotic agents, the optimal antiplatelet regimen in elective patients undergoing complex percutaneous coronary interventions is still debated. Aim of the INtegrilin plus STenting to Avoid myocardial Necrosis Trial (INSTANT) will be to assess the safety and efficacy of routine usage of the glycoprotein IIb/IIIa inhibitor eptifibatide in subjects already treated with aspirin and clopidogrel, and undergoing implantation of at least 2 drug-eluting stents in the same lesion, thus identifying a clinically stable but anatomically complex patient subset.

DESIGN: This will be a single-blind, placebo-controlled multicenter randomized trial METHODS:

Patients with stable coronary artery disease, undergoing percutaneous coronary intervention (PCI) by means of implantation of >33 mm of DES (eg with two 23-mm DES, or one 32-mm and one 12-mm DES), will be randomized, after administration of aspirin and clopidogrel (600 mg loading dose recommended), to eptifibatide and unfractioned heparin according to the ESPRIT protocol vs placebo and unfractioned heparin. Blood draws for CK-MB mass, total CK and cardiac troponin levels will be taken at baseline, 6 and 12 hours post-procedurally. Patients will be followed for clinical events by direct visit or phone contact up to 6 months. The primary end-point of the study will be the rate of abnormal post-PCI CK-MB mass values. Secondary end-points will be: the composite of cardiac death, non-fatal myocardial infarction (MI), urgent target vessel revascularization (TVR), and thrombotic bailout GpIIb/IIIa inhibitor therapy within 180 days, and in-hospital, 1-month and 6-month major adverse cardiovascular events (MACE), defined as the composite of cardiac death, non-fatal MI, or urgent TVR.

IMPLICATIONS: The INSTANT Study will test for the first time the beneficial impact of routine GpIIb/IIIa inhibition on top of double oral antiplatelet treatment in clinically stable yet anatomically complex patients undergoing DES-implantation. Results of this single-blind randomized trial will provide important insights to improve the management strategy of patients and outcomes in the current DES era.

Study Design

Study Type:

Interventional

Actual Enrollment :

91 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A RANDOMIZED TRIAL COMPARING EPTIFIBATIDE AND PLACEBO IN PATIENTS WITH DIFFUSE CORONARY DISEASE UNDERGOING DRUG-ELUTING STENTING

Study Start Date :

Oct 1, 2007

Actual Primary Completion Date :

Oct 1, 2009

Actual Study Completion Date :

Oct 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Eptifibatide Intravenous eptifibatide (double bolus [180 microg/kg] followed by infusion [2 microg/kg per minute] for 18 to 24 hours after the procedure).	Drug: Eptifibatide Intravenous eptifibatide (double bolus [180 microg/kg] followed by infusion [2 microg/kg per minute] for 18 to 24 hours after the procedure) vs placebo.
Placebo Comparator: Placebo	Drug: Eptifibatide Intravenous eptifibatide (double bolus [180 microg/kg] followed by infusion [2 microg/kg per minute] for 18 to 24 hours after the procedure) vs placebo.

Arm

Intervention/Treatment

Experimental: Eptifibatide

Intravenous eptifibatide (double bolus [180 microg/kg] followed by infusion [2 microg/kg per minute] for 18 to 24 hours after the procedure).

Drug: Eptifibatide

Intravenous eptifibatide (double bolus [180 microg/kg] followed by infusion [2 microg/kg per minute] for 18 to 24 hours after the procedure) vs placebo.

Placebo Comparator: Placebo

Drug: Eptifibatide

Intravenous eptifibatide (double bolus [180 microg/kg] followed by infusion [2 microg/kg per minute] for 18 to 24 hours after the procedure) vs placebo.

Outcome Measures

Primary Outcome Measures

Abnormal CK-MB level post-PCI [2 weeks]
The primary end point will be the rate of elevated post-procedural peak CK-MB mass ratio values (ie above the upper limit of normal [ULN], eg 1.01*ULN, according to each participating hospital laboratory).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

male or female able to understand and sign a witnessed informed consent,
age ≥ 18 years
patients with stable (Canadian Cardiovascular Society I-IV) or unstable angina pectoris (but with the most recent anginal episode occurring >48 hours before the procedure [provided that the most recent CK-MB mass levels are within the limits of normal]) or documented silent ischemia
stable hemodynamic conditions (systolic blood pressure>100, heart rate>40 and <100)
no clinical and ECG changes suggestive of ongoing acute or recent (<48 hours) myocardial infarction.

Exclusion Criteria:

female sex with childbearing potential
age <18 years
ongoing or recent episode (<48 hours) of unstable coronary artery disease (including both ST-elevation and non-ST-elevation acute coronary syndromes) without normalization of CK-MB mass levels
administration of any GP IIb/IIIa inhibitors during the previous 2 weeks,
serum creatinine >2.5 mg/dl or > 350 micromols/l
ongoing serious bleeding or bleeding diathesis
previous stroke in the last 6 months
major surgery within the previous 6 weeks
platelet count <100,000 per mm3
ejection Fraction below 30%
known hypersensitivity or contraindication to aspirin, heparin, clopidogrel or sensitivity to contrast which cannot be adequately pre-medicated
hemodynamic instability (systolic blood pressure<100 mm Hg; heart rate<40 bpm or >100 bpm; complex ventricular arrhythmias; atrioventricular block) requiring balloon counterpulsation or inotropic support
simultaneous participation in another device or drug study (patient must have completed the follow-up phase of any previous study at least 30 days prior to enrollment in this study)
positive clinical history for intracranial neoplasia, arterio-venous malformation, aneurysm
INR ≥ 2.0 or prothrombin time 1.2 times upper limit of normality
clinically manifested reduced liver function
programmed surgery within one month