TIMACS: Early Versus Delayed Timing of Intervention in Patients With Acute Coronary Syndromes

• Sponsor: Population Health Research Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00552513
• Collaborator: Canadian Institutes of Health Research (CIHR) (Other), Hamilton Health Sciences Corporation (Other)
• Enrollment: 3,031
• Location: 1
• Arms: 2
• Duration (Months): 45.1
• Patients Per Site Per Month: 67.2

Study Details

Study Description

Brief Summary

The timing of intervention study is a prospective, randomized, international, multicentre comparison of the relative efficacy, safety, and cost effectiveness of a management strategy of coronary angiography and intervention performed within 24 hours of randomization versus delayed coronary angiography and intervention in patients after 36 hours with acute coronary syndromes (ACS).

Condition or Disease	Intervention/Treatment	Phase
Unstable Angina; Myocardial Infarction	Procedure: Early Coronary Intervention; Procedure: Delayed Coronary Intervention	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 3031 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: An International Randomised Trial of Early Versus Delayed Invasive Strategies in Patients With Non-ST Segment Elevation Acute Coronary Syndromes
• Study Start Date: May 1, 2005
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Feb 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Other: Early Coronary Intervention Coronary angiography and intervention (either percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG] surgery) as soon as possible (within 24 hours of randomisation).	Procedure: Early Coronary Intervention; Perform coronary angiography and intervention (either percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG] surgery) as soon as possible (and within 24 hours of randomisation).
Other: Delayed Coronary Intervention Delayed intervention: Coronary angiography and intervention (either percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG] surgery) any time after 36 hours after randomisation.	Procedure: Delayed Coronary Intervention; Perform coronary angiography and intervention (either percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG] surgery) any time after 36 hours after randomisation.

Outcome Measures

Primary Outcome Measures

1. Composite of Death, Myocardial (re-) Infarction, or Stroke [180 days]

Secondary Outcome Measures

1. First Occurrence of Any Component of the Composite of Death, MI, or Refractory Ischemia [180 days]

2. Composite of Death, MI, Stroke, Refractory Ischemia or Repeat Revascularization at 180 Days [180 days]

3. Stroke at 30 Days and 180 Days [180 days]

4. Need for Mechanical or Pharmacological Coronary Revascularization (i.e. Thrombolysis, PCI, CABG) at Days 30, 90, and 180 [180 days]

5. In-hospital Major Bleeding [Hospital discharge]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients presenting or admitted to hospital with symptoms suspected to represent an acute coronary syndrome (unstable angina or MI without persistent ST elevation) i.e., clinical history consistent with new onset, or a worsening pattern, of characteristic ischemic chest pain or ischemic symptoms occurring at rest or with minimal activity (lasting longer than five minutes or requiring sublingual nitroglycerin for relief of the pain)

2. Able to randomise within 24 hours of the onset of the most recent episode of symptoms

3. At least two of the three following additional criteria:

• Age more than or equal to 60 years

• Troponin T or I or Creatine Kinase - Myocardial Bands (CK-MB) above the upper limit of normal for the local institution

• ElectroCardioGram (ECG) changes compatible with ischemia (i.e., ST depression at least 1 mm in two contiguous leads or T wave inversion mroe than 3 mm or any dynamic ST shift or transient ST elevation)

1. Written informed consent dated and signed

Exclusion Criteria:

1. Age less than 21 years

2. Not a suitable candidate for revascularisation

3. Co-morbid condition with life expectancy less than six months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hamilton Health Sciences	Hamilton	Ontario	Canada	L8L 2X2

Sponsors and Collaborators

• Population Health Research Institute
• Canadian Institutes of Health Research (CIHR)
• Hamilton Health Sciences Corporation

Investigators

• Principal Investigator: Shamir Mehta, MD, MSc, Population Health Research Institute, Hamilton Health Sciences, McMaster University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Population Health Research Institute

Publications

• MICHELANGELO OASIS 5 Steering Committee, Mehta SR, Yusuf S, Granger CB, Wallentin L, Peters RJ, Bassand JP, Budaj A, Joyner C, Chrolavicius S, Fox KA. Design and rationale of the MICHELANGELO Organization to Assess Strategies in Acute Ischemic Syndromes (OASIS)-5 trial program evaluating fondaparinux, a synthetic factor Xa inhibitor, in patients with non-ST-segment elevation acute coronary syndromes. Am Heart J. 2005 Dec;150(6):1107.

• Responsible Party: Population Health Research Institute
• ClinicalTrials.gov Identifier: NCT00552513
• Other Study ID Numbers: FRN: MCT-79654; ISRCTN20993046
• First Posted: Nov 2, 2007
• Last Update Posted: Apr 21, 2022
• Last Verified: Apr 1, 2022

• Keywords provided by Population Health Research Institute: timing; intervention; early; delayed; acute coronary syndromes; PCI; angiography; Non ST-segment elevation myocardial infarction; unstable angina
• Additional relevant MeSH terms: Myocardial Infarction; Acute Coronary Syndrome; Angina, Unstable; Infarction

Study Results

Participant Flow

Arm/Group Title	Early	Delayed
Arm/Group Description	Coronary angiography and intervention (either percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG] surgery) as soon as possible (within 24 hours of randomisation).	Delayed intervention: Coronary angiography and intervention (either percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG] surgery) any time after 36 hours after randomisation.
Period Title: Overall Study
STARTED	1593	1438
COMPLETED	1588	1437
NOT COMPLETED	5	1

Baseline Characteristics

Arm/Group Title	Early	Delayed	Total
Arm/Group Description	Coronary angiography and intervention (either percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG] surgery) as soon as possible (within 24 hours of randomisation).	Delayed intervention: Coronary angiography and intervention (either percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG] surgery) any time after 36 hours after randomisation.	Total of all reporting groups
Overall Participants	1593	1438	3031
Age, Customized (years) [Mean (Standard Deviation) ]
Age	65.1 (0)	65.8 (0)	65.5 (0)
Sex: Female, Male (Count of Participants)
Female	554 34.8%	498 34.6%	1052 34.7%
Male	1039 65.2%	940 65.4%	1979 65.3%

Outcome Measures

1. Primary Outcome

Title	Composite of Death, Myocardial (re-) Infarction, or Stroke
Time Frame	180 days

Outcome Measure Data

Analysis Population Description

All patients were included in the final intention-to-treat analysis. Event rates in the two groups were estimated with the use of the Kaplan-Meier method. The hazard ratio and two-sided 95% confidence intervals were calculated with the use of a Cox proportional-hazards model.

Arm/Group Title	Early Intervention	Delayed Intervention
Arm/Group Description	Coronary angiography to be performed as rapidly as possible and within 24 hours after randomization	Coronary angiography to be performed after a minimum delay of 36 hours after randomization
Measure Participants	1593	1438
Number [participants]	153 9.6%	163 11.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Early Intervention, Delayed Intervention
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.15
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.68 to 1.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	First Occurrence of Any Component of the Composite of Death, MI, or Refractory Ischemia
Time Frame	180 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Early Intervention	Delayed Intervention
Arm/Group Description
Measure Participants	1593	1438
Number [participants]	151 9.5%	186 12.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Early Intervention, Delayed Intervention
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.72
	Confidence Interval	(2-Sided) 95%; 0.58 to 0.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Composite of Death, MI, Stroke, Refractory Ischemia or Repeat Revascularization at 180 Days
Time Frame	180 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Early Intervention	Delayed Intervention
Arm/Group Description
Measure Participants	1593	1438
Number [Eparticipants]	264 16.6%	280 19.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Early Intervention, Delayed Intervention
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.71 to 0.99
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Stroke at 30 Days and 180 Days
Time Frame	180 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Need for Mechanical or Pharmacological Coronary Revascularization (i.e. Thrombolysis, PCI, CABG) at Days 30, 90, and 180
Time Frame	180 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	In-hospital Major Bleeding
Time Frame	Hospital discharge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Early		Delayed
Arm/Group Description	Coronary angiography and intervention (either percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG] surgery) as soon as possible (within 24 hours of randomisation).		Delayed intervention: Coronary angiography and intervention (either percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG] surgery) any time after 36 hours after randomisation.
All Cause Mortality
	Early		Delayed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Early		Delayed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Early		Delayed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

PHRI agreements may vary with individual investigators, but will not prohibit any investigator from publishing. PHRI supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.