Deferred or Immediate Stent Implantation Based on Microvascular Function in STEMI

Study Overview
=================
Brief Summary
-----------------
Timely percutaneous coronary intervention (PCI) with stenting implantation is the current standard treatment for patients with ST-segment elevation myocardial infarction (STEMI). However, stenting in thrombus-laden artery is associated with higher risk of embolization and no-or slow-reflow, leading to larger infarct size and poor prognosis. The SALVAGE study is a prospective, multicenter, randomized, controlled study aimed to optimize the therapeutic strategies (deferred vs. immediate stenting) to protect microvascular function and eventually improve clinical outcomes at 12-months in STEMI.

Detailed Description
-----------------
Methodology: A multicenter, prospective, randomized, controlled clinical study enroll patients with ST-segment elevation myocardial infarction (STEMI) intended for PCI with stenting implantation. Eligible patients are randomly assigned to the immediate stenting group or delayed stenting group in a 1:1 ratio when residual stenosis >70% and TIMI grade 3 with angiography guidance. The index of microcirculation resistance (IMR) is quantitative analysis by an invasive approach for evaluating post-infarct myocardial microcirculatory perfusion. IMR correlates with the infarct size of patients with acute myocardial infarction and predicts the improvement in left ventricular ejection fraction. Studies have shown that acute myocardial infarction patients with IMR >40 after primary PCI predict adverse long-term clinical outcomes with higher mortality and heart failure rehospitalization rates. According to therapeutic strategies and microvascular function detected by IMR, participants are classified into four groups: immediate stenting with IMR ≥ 40, immediate stenting with IMR < 40, deferred stenting with IMR ≥ 40 and deferred stenting with IMR < 40. All randomized patients will be followed by phone call or clinical visit at 12 months. Patient enrollment and procedure overview: Patients aged from 18 to 80 with STEMI<12h in whom PCI is planned will be screened. Thrombectomy and balloon dilatation will be performed at the operator's discretion to restore an effective antegrade blood flow with TIMI flow grade 3. Patients with residual diameter stenosis >70% visually and TIMI blood flow grade 3 are eligible for including in the study. All patients must provide written informed consent and patients will be randomized to immediate stenting group or deferred stenting group in a 1:1 ratio. All participants in immediate stenting group will be treated with stent implantation immediately. Those assigned to the deferred arm will undergo stenting after an interval of 7±2 days. This interval will be bridged with anti-coagulant and anti-platelet therapy to reduce thrombus burden. All patients in both groups are required to take dual antiplatelet treatment while the application of low molecular weight heparin and glycoprotein IIb/IIIa inhibitor are determined by the operators. All participants are required to perform IMR pre-stenting and post-stenting to evaluate microcirculation function. All randomized patients will be followed up to 12 months to evaluate the prevalence of heart failure, all-cause mortality, recurrent infarction or targeted vessel revascularization. Study follow-up: Clinical follow-up: Participants will be followed by phone calls or clinical visits by study coordinators at 1 month (+/-7 days), 3 months (+/-15 days), 6 months (+/-15 days), 9 months (+/-15 days) and 12 months (+/-30 days) after randomization. Major adverse cardiovascular events (MACEs) will be recorded throughout the study period until last patient has been followed for 12 months.

Official Title
-----------------
Deferred Versus Immediate Stent Implantation for Preventing Microvascular Dysfunction and Improving Clinical Outcomes in Patients With ST-Segment Elevation Myocardial Infarction (SALVAGE)

Conditions
-----------------
Microcirculatory Perfusion, ST Elevation Myocardial Infarction

Intervention / Treatment
-----------------
* Procedure: Deferred or Immediate Stent Implantation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 years old ≤ age ≤ 80 years old; STEMI and the onset time <12h; The culprit lesions are de novo lesion; Sign written informed consent. Exclusion Criteria: Patients are hemodynamically unstable; Infract-related artery diameter stenosis ≤ 70%; Left main disease; AMI caused by surgery, trauma, gastrointestinal bleeding or PCI and complications; AMI occurs in patients who have been hospitalized for other reasons; The investigator judges that the patient has poor compliance and cannot complete the study as required; Life expectancy ≤ 12 months; Heart transplant patients; Definite diagnosis of patients with tumors; Participate in other clinical studies (excluding other trials of this project) and haven't reach the primary endpoints.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IMR<40 and defer PCI<br>Patients whose IMR<40 undergo stent implantation after an interval of 7±2 days. | Procedure: Deferred or Immediate Stent Implantation<br>* IMR can be used to measure the microcirculatory resistance of coronary artery. It is not clear whether the IMR value could determine the time of PCI for STEMI patients.<br>|
| Active Comparator: IMR<40 and immediately PCI<br>Patients whose IMR<40 undergo immediately stent implantation. | Procedure: Deferred or Immediate Stent Implantation<br>* IMR can be used to measure the microcirculatory resistance of coronary artery. It is not clear whether the IMR value could determine the time of PCI for STEMI patients.<br>|
| Experimental: IMR≥40 and defer PCI<br>Patients whose IMR≥40 undergo stent implantation after an interval of 7±2 days. | Procedure: Deferred or Immediate Stent Implantation<br>* IMR can be used to measure the microcirculatory resistance of coronary artery. It is not clear whether the IMR value could determine the time of PCI for STEMI patients.<br>|
| Active Comparator: IMR≥40 and immediately PCI<br>Patients whose IMR≥40 undergo immediately stent implantation. | Procedure: Deferred or Immediate Stent Implantation<br>* IMR can be used to measure the microcirculatory resistance of coronary artery. It is not clear whether the IMR value could determine the time of PCI for STEMI patients.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of heart failure, all-cause death, reinfarction and targeted vessel revascularization within 1 year of STEMI | MACE including the prevalence of heart failure, all-cause death, reinfarction and targeted vessel revascularization will be collected as the primary outcome. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peri-procedural myocardial reperfusion reinjury | Prevalence of in-hospital heart failure, all-cause death, re-myocardial infarction or targeted vessel revascularization. | through hospitalization, an average of 7 days | 
| Procedural success and clinical success | Culprit lesion stenosis<30% in the presence of TIMI 3 grade flow after PCI are regarded as procedural success. Clinical success is determined as procedural success in the absence of in-hospital cardiac death, target vessel myocardial infarction and clinically-driven target lesion revascularization. | postprocedure and through hospitalization, an average of 7 days | 
| ECG ST-segment resolution at 90 minutes after primary PCI | We will compare the differences of the ST-segment resolution at 90 minutes among groups after primary PCI. | 90 minutes postprocedure | 
| Peaks of CK, CK-MB, cTnI and area under CK curve | We will compare the peaks of CK, CK-MB, cTnI and area under CK curve while in hospital. | through hospitalization, an average of 7 days | 
| LVEF detected by echocardiographic indices at 7 days after stenting, 1 month and 12 months after discharge | LVEF will be detected by echocardiographic indices at 7 days after stenting, 1 month and 12 months after discharge | 7 days, 1 month and 12months | 
| Contrast score index and myocardial blood flow detected by myocardial contrast echocardiography 7 days after stenting and 1 month after discharge | Contrast score index and myocardial blood flow detected by myocardial contrast echocardiography 7 days after stenting and 1 month after discharge | 7 days and 1 month | 
| Hospitalization due to heart failure | Prevalence of hospitalization for heart failure will be compared among groups. | 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
deferred stent implantation, immediate stent implantation, microcirculation function, ST Elevation Myocardial Infarction