Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT04894877 |
| Other study ID # |
11-00498-2 |
| Secondary ID |
1R01HL149888 |
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
July 2012 |
| Est. completion date |
March 31, 2026 |
Study information
| Verified date |
July 2023 |
| Source |
NYU Langone Health |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
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
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
