EARLY ACS: Early Glycoprotein IIb/IIIa Inhibition in Patients With Non-ST-segment Elevation Acute Coronary Syndrome (Study P03684AM2)(COMPLETED)

• Sponsor: Organon and Co (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00089895
• Collaborator: Duke Clinical Research Institute (Other)
• Enrollment: 9,406
• Arms: 2
• Actual Duration (Months): 48

Study Details

Study Description

Brief Summary

The purpose of this study is to see if early INTEGRILIN® (eptifibatide) therapy in patients with non-ST-segment elevation acute coronary syndrome (ACS) reduces the occurence of death, heart attack and urgent cardiac intervention (surgery) compared to placebo (with delayed provisional use of eptifibatide).

Condition or Disease	Intervention/Treatment	Phase
Myocardial Ischemia; Acute Coronary Syndrome	Drug: Eptifibatide (Integrilin); Drug: Placebo	Phase 3

Detailed Description

This study will enroll patients who experience symptoms of acute coronary syndrome (experiencing chest pain at rest with episodes lasting at least 10 minutes) and who are planned to undergo invasive surgical procedures after being given study drug for 12 to 96 hours. There are two different treatment groups in this study; approximately half of the patients will go to each group and the likelihood of receiving study drug vs. placebo is 50/50 (like tossing a coin). Medications that are standard of care will be provided to the patients (all patients will be given aspirin and standard hospital doses of one of two other blood thinning drugs - unfractionated heparin (UFH) or low-molecular-weight heparin). Which one patients receive is at the discretion of the Investigator.

Study Design

• Study Type: Interventional
• Actual Enrollment: 9406 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Early Glycoprotein IIb/IIIa Inhibition in Non-ST-segment Elevation Acute Coronary Syndrome: A Randomized, Placebo-Controlled Trial Evaluating the Clinical Benefits of Early Front-loaded Eptifibatide in the Treatment of Patients With Non-ST-segment Elevation Acute Coronary Syndrome (EARLY ACS)
• Actual Study Start Date: Nov 1, 2004
• Actual Primary Completion Date: Nov 1, 2008
• Actual Study Completion Date: Nov 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Eptifibatide Eptifibatide in addition to standard of care such as standard doses of aspirin, unfractionated heparin or low-molecular-weight heparin.	Drug: Eptifibatide (Integrilin); intravenous; 180 mcg/kg bolus followed by infusion of 2 mcg/kg/min for 12 to 96 hours (or longer if necessary to complete the 18- to 24-hour post-PCI infusion period, or up to 120 hours in patients who proceed to CABG [coronary artery bypass graft]); second bolus of 180 mcg/kg administered 10 minutes after first bolus.; Other Names: Integrilin SCH 060936 SCH 60936
Placebo Comparator: Placebo Placebo in addition to standard of care such as standard doses of aspirin, unfractionated heparin or low-molecular-weight heparin.	Drug: Placebo; intravenous; delivery to match eptifibatide to maintain blind

Outcome Measures

Primary Outcome Measures

1. Incidence of the Composite of Death, Myocardial Infarction (MI), Recurrent Ischemia Requiring Urgent Revascularization (RI-UR), and Thrombotic Bail-out. [96 hours after randomization]

Secondary Outcome Measures

1. Incidence of the Composite of Death/MI. [30 days after randomization]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Willing and able to give informed consent and comply with study procedures and follow-up through 1 year.

• Plan to undergo an invasive strategy after receiving study drug for 12 to 96 hours.

• Able to be randomized into the trial within 12 hours of having symptoms of acute coronary syndrome.

• Experiencing symptoms of cardiac ischemia at rest (angina or anginal equivalent) with episode(s) lasting at least 10 minutes and have at least 2 of the following:

• 60 years of age or more

• Electrocardiogram changes (ECG)

• Elevated troponin (protein released in the blood stream in people suffering from acute coronary syndrome) or CK-MB levels

• Or have all 3 of the following:

• Prior history of cardiovascular disease

• Elevated troponin or CK-MB levels

• 50-59 years of age

Exclusion Criteria:

• pregnancy (known or suspected)

• renal dialysis within 30 days prior to randomizing in study

• other serious illnesses or any condition that the investigator feels would pose a significant hazard to the patient if the investigational therapy was to be initiated

• Stroke (hemorrhagic stroke at any time or non-hemorrhagic stroke within previous 7 days), central nervous system damage (such as neoplasm, aneurysm, intracranial surgery), bleeding disorders (including gastrointestinal bleeding), or recent major surgery or major trauma.

• History of certain hematologic problems following treatment with heparin or eptifibatide.

• Therapy with certain related drugs within a short time before randomization into the trial.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Organon and Co
• Duke Clinical Research Institute

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT00089895
• Other Study ID Numbers: P03684
• First Posted: Aug 19, 2004
• Last Update Posted: Feb 15, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Organon and Co: myocardial infarction; acute coronary syndrome; non-ST-segment elevation; eptifibatide; Integrilin; glycoprotein IIb/IIIa inhibitor (GP IIb/IIIa); percutaneous coronary intervention (PCI); coronary artery bypass graph surgery (CABG); catheterization; angina; ischemia; cardiac ischemia; cardiovascular disease
• Additional relevant MeSH terms: Acute Coronary Syndrome; Myocardial Ischemia; Syndrome; Ischemia; Eptifibatide

Study Results

Participant Flow

Pre-assignment Detail	Patients in both treatment groups who were undergoing PCI could receive unblinded eptifibatide provisionally immediately before or during percutaneous coronary intervention (PCI) at the discretion of the investigator.

Arm/Group Title	Eptifibatide	Placebo
Arm/Group Description	Eptifibatide in addition to standard of care which includes usage of aspirin, unfractionated heparin or low-molecular weight heparin.	Placebo in addition to standard of care which includes usage of aspirin, unfractionated heparin or low-molecular weight heparin.
Period Title: Overall Study
STARTED	4722	4684
COMPLETED	4687	4642
NOT COMPLETED	35	42

Baseline Characteristics

Arm/Group Title	Eptifibatide	Placebo	Total
Arm/Group Description	Eptifibatide in addition to standard of care which includes usage of aspirin, unfractionated heparin or low-molecular weight heparin.	Placebo in addition to standard of care which includes usage of aspirin, unfractionated heparin or low-molecular weight heparin.	Total of all reporting groups
Overall Participants	4722	4684	9406
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.4 (10.6)	66.7 (10.7)	66.6 (10.7)
Sex: Female, Male (Count of Participants)
Female	1513 32%	1462 31.2%	2975 31.6%
Male	3209 68%	3222 68.8%	6431 68.4%

Outcome Measures

1. Primary Outcome

Title	Incidence of the Composite of Death, Myocardial Infarction (MI), Recurrent Ischemia Requiring Urgent Revascularization (RI-UR), and Thrombotic Bail-out.
Time Frame	96 hours after randomization

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	Eptifibatide	Placebo
Arm/Group Description	Eptifibatide in addition to standard of care which includes usage of aspirin, unfractionated heparin or low-molecular weight heparin.	Placebo in addition to standard of care which includes usage of aspirin, unfractionated heparin or low-molecular weight heparin.
Measure Participants	4722	4684
Number [percentage of participants]	9.3 0.2%	10.0 0.2%

2. Secondary Outcome

Title	Incidence of the Composite of Death/MI.
Time Frame	30 days after randomization

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	Eptifibatide	Placebo
Arm/Group Description	Eptifibatide in addition to standard of care which includes usage of aspirin, unfractionated heparin or low-molecular weight heparin.	Placebo in addition to standard of care which includes usage of aspirin, unfractionated heparin or low-molecular weight heparin.
Measure Participants	4722	4684
Number [percentage of participants]	11.2 0.2%	12.3 0.3%

Adverse Events

Time Frame	Through hospital discharge or 120 hours after randomization, whichever occurred first.
Arm/Group Title	Eptifibatide		Placebo
Arm/Group Description	Eptifibatide in addition to standard of care which includes usage of aspirin, unfractionated heparin or low-molecular weight heparin.		Placebo in addition to standard of care which includes usage of aspirin, unfractionated heparin or low-molecular weight heparin.
All Cause Mortality
	Eptifibatide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Eptifibatide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	66/4686 (1.4%)		60/4643 (1.3%)
Blood and lymphatic system disorders
ANAEMIA	1/4686 (0%)	1	0/4643 (0%)	0
MICROCYTIC ANAEMIA	1/4686 (0%)	1	0/4643 (0%)	0
Cardiac disorders
PERICARDIAL EFFUSION	0/4686 (0%)	0	1/4643 (0%)	1
Ear and labyrinth disorders
MIDDLE EAR INFLAMMATION	0/4686 (0%)	0	1/4643 (0%)	1
Endocrine disorders
ADRENOCORTICAL INSUFFICIENCY ACUTE	1/4686 (0%)	1	0/4643 (0%)	0
Eye disorders
OPHTHALMOPLEGIA	1/4686 (0%)	1	0/4643 (0%)	0
RETINAL ARTERY OCCLUSION	0/4686 (0%)	0	1/4643 (0%)	1
Gastrointestinal disorders
ABDOMINAL PAIN	1/4686 (0%)	1	0/4643 (0%)	0
ABDOMINAL PAIN UPPER	0/4686 (0%)	0	1/4643 (0%)	1
DIARRHOEA	2/4686 (0%)	2	0/4643 (0%)	0
DIVERTICULUM INTESTINAL	1/4686 (0%)	1	0/4643 (0%)	0
GASTRIC PERFORATION	0/4686 (0%)	0	1/4643 (0%)	1
GASTRIC ULCER HAEMORRHAGE	1/4686 (0%)	1	0/4643 (0%)	0
INTESTINAL ISCHAEMIA	0/4686 (0%)	0	1/4643 (0%)	1
OESOPHAGEAL ULCER	1/4686 (0%)	1	0/4643 (0%)	0
PANCREATITIS	0/4686 (0%)	0	1/4643 (0%)	1
General disorders
ASTHENIA	0/4686 (0%)	0	1/4643 (0%)	1
IMPLANT SITE EFFUSION	1/4686 (0%)	1	0/4643 (0%)	0
INJECTION SITE PAIN	1/4686 (0%)	1	0/4643 (0%)	0
MULTI-ORGAN FAILURE	1/4686 (0%)	1	1/4643 (0%)	1
PYREXIA	3/4686 (0.1%)	3	2/4643 (0%)	2
Hepatobiliary disorders
CHOLANGITIS	0/4686 (0%)	0	1/4643 (0%)	1
CHOLECYSTITIS ACUTE	1/4686 (0%)	1	1/4643 (0%)	1
CHOLELITHIASIS	1/4686 (0%)	1	0/4643 (0%)	0
HEPATIC FAILURE	2/4686 (0%)	2	0/4643 (0%)	0
LIVER DISORDER	0/4686 (0%)	0	1/4643 (0%)	1
Immune system disorders
HYPERSENSITIVITY	0/4686 (0%)	0	1/4643 (0%)	1
Infections and infestations
ABDOMINAL SEPSIS	0/4686 (0%)	0	1/4643 (0%)	1
ABSCESS LIMB	0/4686 (0%)	0	1/4643 (0%)	1
BRONCHITIS	0/4686 (0%)	0	1/4643 (0%)	1
CELLULITIS	1/4686 (0%)	1	0/4643 (0%)	0
ENDOCARDITIS	0/4686 (0%)	0	1/4643 (0%)	1
GASTROENTERITIS	1/4686 (0%)	1	0/4643 (0%)	0
HEPATITIS A	1/4686 (0%)	1	0/4643 (0%)	0
INFECTION	1/4686 (0%)	1	0/4643 (0%)	0
LOBAR PNEUMONIA	2/4686 (0%)	2	0/4643 (0%)	0
LOWER RESPIRATORY TRACT INFECTION	1/4686 (0%)	1	1/4643 (0%)	1
LUNG INFECTION	1/4686 (0%)	1	0/4643 (0%)	0
PERIRECTAL ABSCESS	0/4686 (0%)	0	1/4643 (0%)	1
PNEUMONIA	5/4686 (0.1%)	5	8/4643 (0.2%)	8
POSTOPERATIVE WOUND INFECTION	0/4686 (0%)	0	1/4643 (0%)	1
PULMONARY TUBERCULOSIS	0/4686 (0%)	0	1/4643 (0%)	1
SEPSIS	2/4686 (0%)	2	3/4643 (0.1%)	3
STAPHYLOCOCCAL SEPSIS	1/4686 (0%)	1	0/4643 (0%)	0
URINARY TRACT INFECTION	1/4686 (0%)	1	0/4643 (0%)	0
UROSEPSIS	1/4686 (0%)	1	0/4643 (0%)	0
Injury, poisoning and procedural complications
LUMBAR VERTEBRAL FRACTURE	0/4686 (0%)	0	1/4643 (0%)	1
MEDICATION ERROR	0/4686 (0%)	0	4/4643 (0.1%)	4
Investigations
BLOOD CREATININE INCREASED	1/4686 (0%)	1	0/4643 (0%)	0
INTERNATIONAL NORMALISED RATIO DECREASED	1/4686 (0%)	1	0/4643 (0%)	0
Metabolism and nutrition disorders
HYPERGLYCAEMIA	1/4686 (0%)	1	1/4643 (0%)	1
Musculoskeletal and connective tissue disorders
ARTHRALGIA	1/4686 (0%)	1	0/4643 (0%)	0
MUSCULAR WEAKNESS	1/4686 (0%)	1	0/4643 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BLADDER CANCER	2/4686 (0%)	2	0/4643 (0%)	0
COLON CANCER	1/4686 (0%)	1	0/4643 (0%)	0
GASTROINTESTINAL TRACT ADENOMA	1/4686 (0%)	1	0/4643 (0%)	0
HEPATIC NEOPLASM MALIGNANT	0/4686 (0%)	0	1/4643 (0%)	1
LUNG NEOPLASM MALIGNANT	0/4686 (0%)	0	1/4643 (0%)	1
Nervous system disorders
BRAIN OEDEMA	1/4686 (0%)	1	0/4643 (0%)	0
CEREBRAL INFARCTION	0/4686 (0%)	0	1/4643 (0%)	1
ENCEPHALOPATHY	1/4686 (0%)	1	1/4643 (0%)	1
PARKINSONISM	0/4686 (0%)	0	1/4643 (0%)	1
SYNCOPE	1/4686 (0%)	1	0/4643 (0%)	0
VASCULAR ENCEPHALOPATHY	0/4686 (0%)	0	1/4643 (0%)	1
Psychiatric disorders
CONFUSIONAL STATE	1/4686 (0%)	1	2/4643 (0%)	2
DELIRIUM	0/4686 (0%)	0	1/4643 (0%)	1
HALLUCINATION	0/4686 (0%)	0	1/4643 (0%)	1
Renal and urinary disorders
IGA NEPHROPATHY	1/4686 (0%)	1	0/4643 (0%)	0
NEPHRITIS INTERSTITIAL	1/4686 (0%)	1	0/4643 (0%)	0
NEPHROPATHY TOXIC	0/4686 (0%)	0	1/4643 (0%)	1
NEPHROSCLEROSIS	1/4686 (0%)	1	0/4643 (0%)	0
RENAL FAILURE	6/4686 (0.1%)	6	4/4643 (0.1%)	4
RENAL FAILURE ACUTE	6/4686 (0.1%)	6	5/4643 (0.1%)	5
RENAL FAILURE CHRONIC	2/4686 (0%)	2	0/4643 (0%)	0
RENAL INFARCT	0/4686 (0%)	0	1/4643 (0%)	1
Respiratory, thoracic and mediastinal disorders
ANOXIA	1/4686 (0%)	1	0/4643 (0%)	0
BRONCHOSPASM	0/4686 (0%)	0	1/4643 (0%)	1
COUGH	1/4686 (0%)	1	0/4643 (0%)	0
DYSPNOEA	1/4686 (0%)	1	0/4643 (0%)	0
HYPOXIA	1/4686 (0%)	1	0/4643 (0%)	0
LUNG DISORDER	1/4686 (0%)	1	1/4643 (0%)	1
PLEURAL EFFUSION	2/4686 (0%)	2	0/4643 (0%)	0
PLEURAL FISTULA	1/4686 (0%)	1	0/4643 (0%)	0
PNEUMOTHORAX	1/4686 (0%)	1	1/4643 (0%)	1
PULMONARY CONGESTION	0/4686 (0%)	0	1/4643 (0%)	1
PULMONARY EMBOLISM	1/4686 (0%)	1	1/4643 (0%)	1
RESPIRATORY DISTRESS	0/4686 (0%)	0	2/4643 (0%)	2
RESPIRATORY FAILURE	7/4686 (0.1%)	7	6/4643 (0.1%)	6
Vascular disorders
AORTIC DISSECTION	0/4686 (0%)	0	1/4643 (0%)	1
CIRCULATORY COLLAPSE	1/4686 (0%)	1	0/4643 (0%)	0
PERIPHERAL EMBOLISM	1/4686 (0%)	1	0/4643 (0%)	0
Other (Not Including Serious) Adverse Events
	Eptifibatide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4686 (0%)		0/4643 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.