Trial Outcomes & Findings for International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) (NCT NCT01471522)
NCT ID: NCT01471522
Last Updated: 2023-06-01
Results Overview
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
5179 participants
Primary outcome timeframe
3.2 year follow-up (median)
Results posted on
2023-06-01
Participant Flow
Participant milestones
| Measure |
Invasive Strategy (INV)
Routine invasive strategy with cardiac catheterization followed by revascularization plus optimal medical therapy.
Cardiac catheterization: Narrowed blood vessels can be opened without surgery using stents or bypassed with surgery. To determine the best approach, the doctor must assess the severity of blood vessel narrowings. This procedure is known as cardiac catheterization.
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, allowing more blood flow to the heart.
Percutaneous coronary intervention: done as part of the cardiac catheterization 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.
|
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.
Lifestyle: diet, physical activity, smoking cessation
Medication: antiplatelet, statin, other lipid lowering, antihypertensive, and anti-ischemic medical therapies
|
|---|---|---|
|
Overall Study
STARTED
|
2588
|
2591
|
|
Overall Study
COMPLETED
|
2524
|
2543
|
|
Overall Study
NOT COMPLETED
|
64
|
48
|
Reasons for withdrawal
| Measure |
Invasive Strategy (INV)
Routine invasive strategy with cardiac catheterization followed by revascularization plus optimal medical therapy.
Cardiac catheterization: Narrowed blood vessels can be opened without surgery using stents or bypassed with surgery. To determine the best approach, the doctor must assess the severity of blood vessel narrowings. This procedure is known as cardiac catheterization.
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, allowing more blood flow to the heart.
Percutaneous coronary intervention: done as part of the cardiac catheterization 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.
|
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.
Lifestyle: diet, physical activity, smoking cessation
Medication: antiplatelet, statin, other lipid lowering, antihypertensive, and anti-ischemic medical therapies
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
28
|
22
|
|
Overall Study
Lost to Follow-up
|
36
|
26
|
Baseline Characteristics
International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA)
Baseline characteristics by cohort
| Measure |
Invasive Strategy (INV)
n=2588 Participants
Invasive Strategy (INV)
|
Conservative Strategy
n=2591 Participants
Conservative Strategy
|
Total
n=5179 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
64 years
n=5 Participants
|
64 years
n=7 Participants
|
64 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
606 Participants
n=5 Participants
|
562 Participants
n=7 Participants
|
1168 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1982 Participants
n=5 Participants
|
2029 Participants
n=7 Participants
|
4011 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
372 Participants
n=5 Participants
|
391 Participants
n=7 Participants
|
763 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
2030 Participants
n=5 Participants
|
2022 Participants
n=7 Participants
|
4052 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
186 Participants
n=5 Participants
|
178 Participants
n=7 Participants
|
364 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
8 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
747 Participants
n=5 Participants
|
738 Participants
n=7 Participants
|
1485 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
5 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
96 Participants
n=5 Participants
|
108 Participants
n=7 Participants
|
204 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
1706 Participants
n=5 Participants
|
1697 Participants
n=7 Participants
|
3403 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
7 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
19 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
50 Participants
n=5 Participants
|
|
Region of Enrollment
Africa
|
8 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Region of Enrollment
Asia
|
791 Participants
n=5 Participants
|
786 Participants
n=7 Participants
|
1577 Participants
n=5 Participants
|
|
Region of Enrollment
Europe
|
853 Participants
n=5 Participants
|
865 Participants
n=7 Participants
|
1718 Participants
n=5 Participants
|
|
Region of Enrollment
Latin America
|
239 Participants
n=5 Participants
|
239 Participants
n=7 Participants
|
478 Participants
n=5 Participants
|
|
Region of Enrollment
Middle East
|
10 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Region of Enrollment
North America
|
648 Participants
n=5 Participants
|
652 Participants
n=7 Participants
|
1300 Participants
n=5 Participants
|
|
Region of Enrollment
Pacifica
|
39 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
73 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 3.2 year follow-up (median)Outcome measures
| Measure |
Invasive Strategy (INV)
n=2588 Participants
Invasive Strategy (INV)
|
Conservative Strategy
n=2591 Participants
Conservative Strategy
|
|---|---|---|
|
Primary Composite Outcome: Death From Cardiovascular Causes, Myocardial Infarction, or Hospitalization for Unstable Angina, Heart Failure, or Resuscitated Cardiac Arrest
|
318 Participants
|
352 Participants
|
PRIMARY outcome
Timeframe: 5 yearsThis measure represents the estimated cumulative probability of experiencing the primary endpoint within the indicated timeframe in each treatment group. The interpretation of the measure is similar to Kaplan-Meier event rates. Estimates are expressed as percentages ranging from 0% (endpoint is certain not to occur) to 100% (endpoint is certain to occur).
Outcome measures
| Measure |
Invasive Strategy (INV)
n=2588 Participants
Invasive Strategy (INV)
|
Conservative Strategy
n=2591 Participants
Conservative Strategy
|
|---|---|---|
|
Cumulative Event Rate of Primary Composite Outcome (Death From Cardiovascular Causes, Myocardial Infarction, or Hospitalization for Unstable Angina, Heart Failure, or Resuscitated Cardiac Arrest)
At 6 months
|
5.3 cumulative event rate - %
|
3.4 cumulative event rate - %
|
|
Cumulative Event Rate of Primary Composite Outcome (Death From Cardiovascular Causes, Myocardial Infarction, or Hospitalization for Unstable Angina, Heart Failure, or Resuscitated Cardiac Arrest)
At 1 year
|
7.0 cumulative event rate - %
|
5.4 cumulative event rate - %
|
|
Cumulative Event Rate of Primary Composite Outcome (Death From Cardiovascular Causes, Myocardial Infarction, or Hospitalization for Unstable Angina, Heart Failure, or Resuscitated Cardiac Arrest)
At 2 years
|
9.0 cumulative event rate - %
|
9.5 cumulative event rate - %
|
|
Cumulative Event Rate of Primary Composite Outcome (Death From Cardiovascular Causes, Myocardial Infarction, or Hospitalization for Unstable Angina, Heart Failure, or Resuscitated Cardiac Arrest)
At 3 years
|
11.3 cumulative event rate - %
|
12.7 cumulative event rate - %
|
|
Cumulative Event Rate of Primary Composite Outcome (Death From Cardiovascular Causes, Myocardial Infarction, or Hospitalization for Unstable Angina, Heart Failure, or Resuscitated Cardiac Arrest)
At 4 years
|
13.3 cumulative event rate - %
|
15.5 cumulative event rate - %
|
|
Cumulative Event Rate of Primary Composite Outcome (Death From Cardiovascular Causes, Myocardial Infarction, or Hospitalization for Unstable Angina, Heart Failure, or Resuscitated Cardiac Arrest)
At 5 years
|
16.4 cumulative event rate - %
|
18.2 cumulative event rate - %
|
PRIMARY outcome
Timeframe: 5 yearsOutcome measures
| Measure |
Invasive Strategy (INV)
n=2588 Participants
Invasive Strategy (INV)
|
Conservative Strategy
n=2591 Participants
Conservative Strategy
|
|---|---|---|
|
Number of Participants That Experienced Death From Cardiovascular Causes or Myocardial Infarction
|
276 Participants
|
314 Participants
|
PRIMARY outcome
Timeframe: 5 yearsThis measure represents the estimated cumulative probability of experiencing Death from cardiovascular causes or myocardial infarction within the indicated timeframe in each treatment group. The interpretation of the measure is similar to Kaplan-Meier event rates. Estimates are expressed as percentages ranging from 0% (endpoint is certain not to occur) to 100% (endpoint is certain to occur).
Outcome measures
| Measure |
Invasive Strategy (INV)
n=2588 Participants
Invasive Strategy (INV)
|
Conservative Strategy
n=2591 Participants
Conservative Strategy
|
|---|---|---|
|
Cumulative Event Rate of Death From Cardiovascular Causes or Myocardial Infarction
At 6 months
|
4.8 Cumulative event rate -- %
|
2.9 Cumulative event rate -- %
|
|
Cumulative Event Rate of Death From Cardiovascular Causes or Myocardial Infarction
At 1 year
|
6.2 Cumulative event rate -- %
|
4.6 Cumulative event rate -- %
|
|
Cumulative Event Rate of Death From Cardiovascular Causes or Myocardial Infarction
At 2 years
|
7.9 Cumulative event rate -- %
|
8.2 Cumulative event rate -- %
|
|
Cumulative Event Rate of Death From Cardiovascular Causes or Myocardial Infarction
At 3 years
|
9.7 Cumulative event rate -- %
|
11.0 Cumulative event rate -- %
|
|
Cumulative Event Rate of Death From Cardiovascular Causes or Myocardial Infarction
At 4 years
|
11.7 Cumulative event rate -- %
|
13.9 Cumulative event rate -- %
|
|
Cumulative Event Rate of Death From Cardiovascular Causes or Myocardial Infarction
At 5 years
|
14.2 Cumulative event rate -- %
|
16.5 Cumulative event rate -- %
|
PRIMARY outcome
Timeframe: 5 yearsOutcome measures
| Measure |
Invasive Strategy (INV)
n=2588 Participants
Invasive Strategy (INV)
|
Conservative Strategy
n=2591 Participants
Conservative Strategy
|
|---|---|---|
|
Number of Participants That Experienced Death From Any Cause
|
145 Participants
|
144 Participants
|
PRIMARY outcome
Timeframe: 5 yearsOutcome measures
| Measure |
Invasive Strategy (INV)
n=2588 Participants
Invasive Strategy (INV)
|
Conservative Strategy
n=2591 Participants
Conservative Strategy
|
|---|---|---|
|
Cumulative Event Rate of Death From Any Cause
At 6 months
|
0.8 Cumulative event rate -- %
|
0.4 Cumulative event rate -- %
|
|
Cumulative Event Rate of Death From Any Cause
At 1 year
|
1.7 Cumulative event rate -- %
|
1.0 Cumulative event rate -- %
|
|
Cumulative Event Rate of Death From Any Cause
At 2 years
|
2.8 Cumulative event rate -- %
|
2.9 Cumulative event rate -- %
|
|
Cumulative Event Rate of Death From Any Cause
At 3 years
|
4.3 Cumulative event rate -- %
|
4.3 Cumulative event rate -- %
|
|
Cumulative Event Rate of Death From Any Cause
At 4 years
|
6.5 Cumulative event rate -- %
|
6.4 Cumulative event rate -- %
|
|
Cumulative Event Rate of Death From Any Cause
At 5 years
|
9.0 Cumulative event rate -- %
|
8.3 Cumulative event rate -- %
|
PRIMARY outcome
Timeframe: 5 yearsOutcome measures
| Measure |
Invasive Strategy (INV)
n=2588 Participants
Invasive Strategy (INV)
|
Conservative Strategy
n=2591 Participants
Conservative Strategy
|
|---|---|---|
|
Number of Participants That Experienced Myocardial Infarction
|
210 Participants
|
233 Participants
|
PRIMARY outcome
Timeframe: 5 yearsOutcome measures
| Measure |
Invasive Strategy (INV)
n=2588 Participants
Invasive Strategy (INV)
|
Conservative Strategy
n=2591 Participants
Conservative Strategy
|
|---|---|---|
|
Cumulative Event Rate of Myocardial Infarction
At 6 months
|
4.3 Cumulative event rate -- %
|
2.6 Cumulative event rate -- %
|
|
Cumulative Event Rate of Myocardial Infarction
At 1 year
|
5.3 Cumulative event rate -- %
|
3.8 Cumulative event rate -- %
|
|
Cumulative Event Rate of Myocardial Infarction
At 2 years
|
6.3 Cumulative event rate -- %
|
6.5 Cumulative event rate -- %
|
|
Cumulative Event Rate of Myocardial Infarction
At 3 years
|
7.7 Cumulative event rate -- %
|
8.5 Cumulative event rate -- %
|
|
Cumulative Event Rate of Myocardial Infarction
At 4 years
|
8.9 Cumulative event rate -- %
|
10.1 Cumulative event rate -- %
|
|
Cumulative Event Rate of Myocardial Infarction
At 5 years
|
10.3 Cumulative event rate -- %
|
11.9 Cumulative event rate -- %
|
PRIMARY outcome
Timeframe: 5 yearsPopulation: Invasive = 2588; Conservative = 2591
The primary composite outcome includes death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest.
Outcome measures
| Measure |
Invasive Strategy (INV)
n=5179 Participants
Invasive Strategy (INV)
|
Conservative Strategy
Conservative Strategy
|
|---|---|---|
|
Estimated Difference in Cumulative Event Rate ( %) of Primary Composite Outcome: Invasive Minus Conservative
At 6 months
|
1.9 cumulative event rate - %
Interval 0.8 to 3.0
|
—
|
|
Estimated Difference in Cumulative Event Rate ( %) of Primary Composite Outcome: Invasive Minus Conservative
At 1 year
|
1.5 cumulative event rate - %
Interval 0.2 to 2.9
|
—
|
|
Estimated Difference in Cumulative Event Rate ( %) of Primary Composite Outcome: Invasive Minus Conservative
At 2 years
|
-0.5 cumulative event rate - %
Interval -2.1 to 1.1
|
—
|
|
Estimated Difference in Cumulative Event Rate ( %) of Primary Composite Outcome: Invasive Minus Conservative
At 3 years
|
-1.3 cumulative event rate - %
Interval -3.2 to 0.6
|
—
|
|
Estimated Difference in Cumulative Event Rate ( %) of Primary Composite Outcome: Invasive Minus Conservative
At 4 years
|
-2.2 cumulative event rate - %
Interval -4.4 to 0.0
|
—
|
|
Estimated Difference in Cumulative Event Rate ( %) of Primary Composite Outcome: Invasive Minus Conservative
At 5 years
|
-1.8 cumulative event rate - %
Interval -4.7 to 1.0
|
—
|
PRIMARY outcome
Timeframe: 5 yearsPopulation: Invasive = 2588; Conservative = 2591
Outcome measures
| Measure |
Invasive Strategy (INV)
n=5179 Participants
Invasive Strategy (INV)
|
Conservative Strategy
Conservative Strategy
|
|---|---|---|
|
Estimated Difference in Cumulative Event Rate of Death From Cardiovascular Causes: Invasive Minus Conservative or Myocardial Infarction Between Invasive and Conservative Strategies
At 6 months
|
1.9 cumulative event rate - %
Interval 0.9 to 3.0
|
—
|
|
Estimated Difference in Cumulative Event Rate of Death From Cardiovascular Causes: Invasive Minus Conservative or Myocardial Infarction Between Invasive and Conservative Strategies
At 1 year
|
1.6 cumulative event rate - %
Interval 0.4 to 2.8
|
—
|
|
Estimated Difference in Cumulative Event Rate of Death From Cardiovascular Causes: Invasive Minus Conservative or Myocardial Infarction Between Invasive and Conservative Strategies
At 2 years
|
-0.3 cumulative event rate - %
Interval -1.8 to 1.2
|
—
|
|
Estimated Difference in Cumulative Event Rate of Death From Cardiovascular Causes: Invasive Minus Conservative or Myocardial Infarction Between Invasive and Conservative Strategies
At 3 years
|
-1.3 cumulative event rate - %
Interval -3.1 to 0.5
|
—
|
|
Estimated Difference in Cumulative Event Rate of Death From Cardiovascular Causes: Invasive Minus Conservative or Myocardial Infarction Between Invasive and Conservative Strategies
At 4 years
|
-2.2 cumulative event rate - %
Interval -4.4 to -0.1
|
—
|
|
Estimated Difference in Cumulative Event Rate of Death From Cardiovascular Causes: Invasive Minus Conservative or Myocardial Infarction Between Invasive and Conservative Strategies
At 5 years
|
-2.3 cumulative event rate - %
Interval -5.0 to 0.4
|
—
|
PRIMARY outcome
Timeframe: 5 yearsPopulation: Invasive = 2588; Conservative = 2591
Outcome measures
| Measure |
Invasive Strategy (INV)
n=5179 Participants
Invasive Strategy (INV)
|
Conservative Strategy
Conservative Strategy
|
|---|---|---|
|
Estimated Difference in Cumulative Event Rate of Death From Any Cause: Invasive Minus Conservative
At 6 months
|
0.4 cumulative event rate - %
Interval 0.0 to 0.8
|
—
|
|
Estimated Difference in Cumulative Event Rate of Death From Any Cause: Invasive Minus Conservative
At 1 year
|
0.7 cumulative event rate - %
Interval 0.0 to 1.3
|
—
|
|
Estimated Difference in Cumulative Event Rate of Death From Any Cause: Invasive Minus Conservative
At 2 years
|
-0.1 cumulative event rate - %
Interval -1.0 to 0.9
|
—
|
|
Estimated Difference in Cumulative Event Rate of Death From Any Cause: Invasive Minus Conservative
At 3 years
|
0 cumulative event rate - %
Interval -1.2 to 1.2
|
—
|
|
Estimated Difference in Cumulative Event Rate of Death From Any Cause: Invasive Minus Conservative
At 4 years
|
0.1 cumulative event rate - %
Interval -1.5 to 1.8
|
—
|
|
Estimated Difference in Cumulative Event Rate of Death From Any Cause: Invasive Minus Conservative
At 5 years
|
0.7 cumulative event rate - %
Interval -1.6 to 3.1
|
—
|
PRIMARY outcome
Timeframe: 5 yearsPopulation: Invasive = 2588; Conservative = 2591
Outcome measures
| Measure |
Invasive Strategy (INV)
n=5179 Participants
Invasive Strategy (INV)
|
Conservative Strategy
Conservative Strategy
|
|---|---|---|
|
Estimated Difference in Cumulative Event Rate of Myocardial Infarction: Invasive Minus Conservative
At 6 months
|
1.8 cumulative event rate - %
Interval 0.8 to 2.8
|
—
|
|
Estimated Difference in Cumulative Event Rate of Myocardial Infarction: Invasive Minus Conservative
At 1 year
|
1.5 cumulative event rate - %
Interval 0.3 to 2.6
|
—
|
|
Estimated Difference in Cumulative Event Rate of Myocardial Infarction: Invasive Minus Conservative
At 2 years
|
-0.1 cumulative event rate - %
Interval -1.5 to 1.2
|
—
|
|
Estimated Difference in Cumulative Event Rate of Myocardial Infarction: Invasive Minus Conservative
At 3 years
|
-0.7 cumulative event rate - %
Interval -2.3 to 0.8
|
—
|
|
Estimated Difference in Cumulative Event Rate of Myocardial Infarction: Invasive Minus Conservative
At 4 years
|
-1.2 cumulative event rate - %
Interval -3.0 to 0.6
|
—
|
|
Estimated Difference in Cumulative Event Rate of Myocardial Infarction: Invasive Minus Conservative
At 5 years
|
-1.6 cumulative event rate - %
Interval -3.9 to 0.7
|
—
|
Adverse Events
Invasive Strategy (INV)
Serious events: 318 serious events
Other events: 0 other events
Deaths: 145 deaths
Conservative Strategy
Serious events: 352 serious events
Other events: 0 other events
Deaths: 144 deaths
Serious adverse events
| Measure |
Invasive Strategy (INV)
n=2588 participants at risk
Invasive Strategy (INV)
|
Conservative Strategy
n=2591 participants at risk
Conservative Strategy
|
|---|---|---|
|
Cardiac disorders
Cardiovascular Death
|
3.6%
92/2588 • Number of events 92 • 5 years
SAEs were collected as part of the Primary Composite Outcome
|
4.3%
111/2591 • Number of events 111 • 5 years
SAEs were collected as part of the Primary Composite Outcome
|
|
Cardiac disorders
Procedural Myocardial Infarction
|
2.7%
70/2588 • Number of events 70 • 5 years
SAEs were collected as part of the Primary Composite Outcome
|
0.93%
24/2591 • Number of events 24 • 5 years
SAEs were collected as part of the Primary Composite Outcome
|
|
Cardiac disorders
Non-procedural Myocardial Infarction
|
5.0%
130/2588 • Number of events 130 • 5 years
SAEs were collected as part of the Primary Composite Outcome
|
7.6%
196/2591 • Number of events 196 • 5 years
SAEs were collected as part of the Primary Composite Outcome
|
|
Cardiac disorders
Hospitalization for Unstable Angina
|
0.62%
16/2588 • Number of events 16 • 5 years
SAEs were collected as part of the Primary Composite Outcome
|
1.2%
32/2591 • Number of events 32 • 5 years
SAEs were collected as part of the Primary Composite Outcome
|
|
Cardiac disorders
Hospitalization for Heart Failure
|
2.0%
51/2588 • Number of events 51 • 5 years
SAEs were collected as part of the Primary Composite Outcome
|
0.96%
25/2591 • Number of events 25 • 5 years
SAEs were collected as part of the Primary Composite Outcome
|
|
Cardiac disorders
Resuscitated Cardiac Arrest
|
0.19%
5/2588 • Number of events 5 • 5 years
SAEs were collected as part of the Primary Composite Outcome
|
0.19%
5/2591 • Number of events 5 • 5 years
SAEs were collected as part of the Primary Composite Outcome
|
|
Cardiac disorders
Stroke
|
1.7%
45/2588 • Number of events 45 • 5 years
SAEs were collected as part of the Primary Composite Outcome
|
1.5%
38/2591 • Number of events 38 • 5 years
SAEs were collected as part of the Primary Composite Outcome
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place