ISCHEMIA-EXTEND (Extended Follow-up)
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|ClinicalTrials.gov Identifier: NCT04894877|
Recruitment Status : Active, not recruiting
First Posted : May 20, 2021
Last Update Posted : September 21, 2022
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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.
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
|Condition or disease||Intervention/treatment|
|Cardiovascular Diseases Coronary Disease Coronary Artery Disease Heart Diseases Myocardial Ischemia||Procedure: cardiac catheterization Procedure: coronary artery bypass graft surgery Procedure: percutaneous coronary intervention Behavioral: Lifestyle Drug: Medication|
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.
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 :||Observational|
|Actual Enrollment :||4825 participants|
|Official Title:||International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) Extended Follow-up|
|Actual Study Start Date :||July 2012|
|Estimated Primary Completion Date :||March 31, 2026|
|Estimated Study Completion Date :||March 31, 2026|
Active Comparator: Invasive Strategy (INV)
Routine invasive strategy with cardiac catheterization followed by revascularization plus optimal medical therapy.
Procedure: cardiac catheterization
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 Name: Cath
Procedure: coronary artery bypass graft surgery
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 Name: CABG
Procedure: percutaneous coronary intervention
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 Name: PCI
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.
diet, physical activity, smoking cessation
Other Name: Behavior change
antiplatelet, statin, other lipid lowering, antihypertensive, and anti-ischemic medical therapies
Other Name: Pharmacologic Therapy
- Cumulative Event Rate of Death: All-Cause [ Time Frame: Year 10 (Range: 6-13 years) ]Cumulative event rate of death from all causes.
- Cumulative Event Rate of Cardiovascular (CV) Death [ Time Frame: Year 10 (Range 6-13 years) ]Cumulative event rate of death from cardiovascular causes.
- Cumulative Event Rate of Non-CV Death [ Time Frame: Year 10 (Range: 6-13 years) ]Cumulative event rate of death from non-cardiovascular causes.
- Cumulative Event Rate of Death by High Risk Subgroups [ Time Frame: Year 10 (Range 6-13 years) ]Angiographic and clinical risk variables.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||21 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
|Sampling Method:||Non-Probability Sample|
- Alive at the end of the initial follow-up period for ISCHEMIA
- Participants who withdrew consent during initial trial phase
- Participants who declined participation in long-term follow-up
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04894877
|Study Chair:||Judith S Hochman, MD||New York University|
|Principal Investigator:||David J Maron, MD||Stanford University|
Documents provided by NYU Langone Health:
|Responsible Party:||NYU Langone Health|
|Other Study ID Numbers:||
1R01HL149888 ( U.S. NIH Grant/Contract )
|First Posted:||May 20, 2021 Key Record Dates|
|Last Update Posted:||September 21, 2022|
|Last Verified:||September 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Yes|
|Plan Description:||Data from the follow-up analysis will be made available 2 years after the main results paper is published.|
Statistical Analysis Plan (SAP)
|Time Frame:||Beginning 9 months and ending 36 months following article|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
Coronary Artery Disease
Arterial Occlusive Diseases