- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04894877
ISCHEMIA-EXTEND (Extended Follow-up)
International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) Extended Follow-up
The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) Extended Follow-up (ISCHEMIA-EXTEND) is the long-term follow-up of randomized, surviving participants in ISCHEMIA. ISCHEMIA was an NHLBI-supported trial that randomized 5,179 participants with stable ischemic heart disease to two different management strategies: 1) an initial invasive strategy (INV) of cardiac catheterization and revascularization when feasible plus guideline-directed medical therapy (GDMT), or 2) an initial conservative strategy (CON) of GDMT. The trial did not demonstrate a reduction in the primary endpoint with an initial invasive strategy. There was an excess of procedural myocardial infarction (MI) and a reduction in spontaneous MI in the INV group. Prior evidence suggests that spontaneous MI carries a higher risk of subsequent death than procedural MI. There was a late separation in the cardiovascular (CV) mortality curves over a median of 3.2 years follow-up in ISCHEMIA. The MI incidence curves crossed at approximately 2 years. However, during the trial follow-up phase there were excess non-CV deaths in the invasive strategy. Therefore, it is imperative to ascertain long-term vital status to provide patients and clinicians with robust evidence on whether there are differences between management strategies and to increase precision around the treatment effect estimates for risk of all-cause, CV and non-CV death over the long-term.
Overarching Goal:
To assess the effect of an initial invasive strategy on long-term all-cause, CV and non-CV mortality compared with an initial conservative strategy in SIHD patients with at least moderate ischemia on stress testing, over 10 years median follow-up.
Condition: Coronary Disease Procedure: Observational Phase: Phase III per NIH Condition: Cardiovascular Diseases Procedure: Observational Phase: Phase III per NIH Condition: Heart Diseases Procedure: Observational Phase: Phase III per NIH
Study Overview
Status
Conditions
Detailed Description
The primary goals of all therapies are to enable patients to feel better and/or live longer. ISCHEMIA provided definitive data on the benefit of INV on quality of life. However, mortality is the most objective and compelling clinical outcome. Strategies that reduce deaths over the long term are of greatest interest to patients and physicians. Long-term follow-up of the ISCHEMIA trial cohort to assess all-cause, CV and non-CV mortality by treatment group is particularly important given that the primary results show relatively late crossing of the event curves, an overall reduction in spontaneous MI with INV, and late divergence of CV death curves in favor of the INV strategy but with an excess of non-CV deaths.
DESIGN NARRATIVE, INCLUDING MODIFICATIONS DURING THE TRIAL:
The investigators will conduct a long-term ascertainment of all-cause, CV and non-CV mortality for surviving ISCHEMIA participants. The limited follow-up after the observed reduction in spontaneous MI events may not have been long enough to observe a mortality benefit, and this makes it imperative to assess long-term all-cause, CV and non-CV mortality to determine whether an initial invasive strategy reduces the risk of death years later, as seen in other trials with crossing curves, e.g., STICH, a randomized trial comparing a strategy of surgical revascularization to GDMT alone in patients with SIHD and LVEF <35%.
Furthermore, with additional accrual of deaths, the investigators will provide estimates on the impact of INV in the highest risk subgroup, those with coronary artery anatomy for whom practice guidelines have recommended CABG to improve survival (3-vessel CAD and 2-vessel CAD with proximal LAD stenosis). Equally important is to improve precision around the point estimates of the treatment effect for all-cause, CV and non-CV mortality for the trial overall and in important subgroups to efficiently maximize the substantial investment by of NHLBI, patients, and study teams.
Vital status data will be collected in a rigorous manner from high-quality vital statistics registries, medical records, or by contacting participants and their next of kin.
ISCHEMIA-EXTEND will also follow eligible participants from the NHLBI-funded ISCHEMIA-CKD trial with the same methodology as for the main trial with separate analyses. They will be referred to as ISCHEMIA-EXTEND for the main trial and ISCHEMIA-CKD EXTEND for the CKD trial.
PARTICIPATING COUNTRIES:
North America: Canada; Mexico; USA South America: Argentina; Brazil; Peru Asia: China; India; Japan; Malaysia; Singapore; Thailand; Russian Federation Pacifica: Australia; New Zealand Europe: Austria; Belgium; France; Germany; Hungary; Italy; Lithuania; Macedonia; Netherlands; Poland; Portugal; Romania; Serbia; Spain; Sweden; Switzerland; UK Middle East: Egypt; Israel; Saudi Arabia Africa: South Africa
Study Type
Enrollment (Actual)
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Alive at the end of the initial follow-up period for ISCHEMIA
Exclusion Criteria:
- Participants who withdrew consent during initial trial phase
- Participants who declined participation in long-term follow-up
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Active Comparator: Invasive Strategy (INV)
Routine invasive strategy with cardiac catheterization followed by revascularization plus optimal medical therapy.
|
Narrowed blood vessels can be opened without surgery using stents or can be bypassed with surgery.
To determine which is the best approach for you the doctor needs to look at your blood vessels to see where the narrowings are and how much narrowing there is.
This is done by a procedure known as a cardiac catheterization.
Other Names:
Artery narrowing is bypassed during surgery with a healthy artery or vein from another part of the body.
This is known as coronary artery bypass grafting, or CABG (said, "cabbage").
The surgery creates new routes around narrowed and blocked heart arteries.
This allows more blood flow to the heart.
Other Names:
Percutaneous coronary intervention may be done as part of the cardiac catheterization procedure.
With this procedure a small, hollow, mesh tube (stent) is inserted into the narrowed part of the artery.
The stent pushes the plaque against the artery wall, and opens the vessel to allow better blood flow.
Other Names:
|
Active Comparator: Conservative Strategy
Optimal medical therapy with cardiac catheterization and revascularization reserved for patients with acute coronary syndrome, ischemic heart failure, resuscitated cardiac arrest or refractory symptoms.
|
antiplatelet, statin, other lipid lowering, antihypertensive, and anti-ischemic medical therapies
Other Names:
diet, physical activity, smoking cessation
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cumulative Event Rate of Death: All-Cause
Time Frame: Year 10 (Range: 6-13 years)
|
Cumulative event rate of death from all causes.
|
Year 10 (Range: 6-13 years)
|
Cumulative Event Rate of Cardiovascular (CV) Death
Time Frame: Year 10 (Range 6-13 years)
|
Cumulative event rate of death from cardiovascular causes.
|
Year 10 (Range 6-13 years)
|
Cumulative Event Rate of Non-CV Death
Time Frame: Year 10 (Range: 6-13 years)
|
Cumulative event rate of death from non-cardiovascular causes.
|
Year 10 (Range: 6-13 years)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cumulative Event Rate of Death by High Risk Subgroups
Time Frame: Year 10 (Range 6-13 years)
|
Angiographic and clinical risk variables.
|
Year 10 (Range 6-13 years)
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Judith S Hochman, MD, New York University
- Principal Investigator: David J Maron, MD, Stanford University
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 11-00498-2
- 1R01HL149888 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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