Clinical trial NCT04493840: Randomized Evaluation of Shenfu Injection to Reduce Myocardial Injury
Official title: Effect of Shenfu Injection on Myocardial Injury in Patients With Acute ST Segment Elevation Myocardial Infarction After Primary Percutaneous Coronary Intervention: A Multicenter, Randomized, Double-Blinded, Parallel-Group, Placebo-Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Myocardial Infarction
Lead sponsor: Beijing Anzhen Hospital
Sponsor class: OTHER
First posted: 2020-07-30
Enrollment: 326
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study aims to evaluate whether perioperative use of Shenfu Injection, as compared to placebo, could reduce infarct size assessed by cardiac magnetic resonance (CMR) in patients with acute anterior ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).

Detailed description: Shenfu injection is a traditional Chinese medicine formulation containing ginseng (Panax; family: Araliaceae) and aconite (Radix aconiti lateralis preparata, Aconitum carmichaeli Debx; family: Ranunculaceae) with Ginsenosides and aconite alkaloids as the main active ingredients. Its quality is strictly controlled in compliance with the standard of the China Ministry of Public Health (official approval code: certification number Z20043117; No. 110804, Ya'an, China). Animal studies have shown that Shenfu injection has protective effects against reperfusion injury through multiple pharmacologic effects, including scavenging free radicals, inhibiting inflammatory mediators, suppressing cell apoptosis, and inhibiting calcium overload. However, few data are available regarding its efficacy in humans. We aimed to determine whether perioperative use of Shenfu injection, as compared to placebo, might reduce infarct size in patients with STEMI undergoing primary PCI.

Eligibility criteria: Inclusion Criteria:

1. Age ≥18 and \<75 years.
2. First-time acute anterior STEMI scheduled for primary PCI.
3. ST segment elevation in at least two contiguous precordial leads according to electrocardiogram (\>30 min).
4. Symptoms onset ≤12 hours.
5. The presence of proximal or middle left anterior descending branch (LAD) occlusion with pre-PCI TIMI flow 0 or 1 according to baseline coronary angiogram.
6. Written informed consent.

Exclusion Criteria:

1. Cardiogenic shock, serious heart failure (Killip class III or above), malignant ventricular arrhythmia, or mechanical complications.
2. Post cardiopulmonary resuscitation (CPR) (including cardioversion).
3. Patients who have received thrombolytic therapy or upstream GPIIb/IIIa inhibitors (GPI).
4. Uncontrolled hypertension (systolic BP ≥180 mm Hg or a diastolic BP ≥110 mmHg).
5. Prior myocardial infarction, PCI or coronary artery bypass graft.
6. Known severe hepatic insufficiency (AST/ALT \>3-fold the upper limit of normal value) or known renal insufficiency.
7. Malignant tumor, lymphoma, HIV-positive, or cirrhosis with life expectancy \<1 year.
8. Patients with active bleeding, intracranial hemorrhage, major surgery or trauma within 1 months, or ischemic stroke or transient ischemic attack (TIA) within 6 months.
9. History of anemia (hemoglobin\<90g/L) or thrombocytopenia (thrombocyte\<100×109/L).
10. Patients who require simultaneous intervention of left main disease during primary PCI or those with multi-vessel disease who plan to intervene in non-culprit vessels within 7 days (simultaneous or staged).
11. Scheduled for CABG within one month after randomization.
12. Pregnancy, lactation, or potentially fertile women.
13. Patients who have known to be allergic to Shenfu Injection or its components or patients with serious adverse effect.
14. Patients with contraindication to CMR (metal foreign body in the body, claustrophobia, etc.).
15. Participation in other clinical trial in recent 3 months.
16. Patients who cannot complete this trial or comply with the protocol.

Primary outcomes:
measure: Infarct size (% of left ventricular mass)
timeFrame: 5±2 days after PCI
Secondary outcomes:
measure: Microvascular obstruction (% of left ventricular mass)
timeFrame: 5±2 days after PCI
measure: Intramyocardial hemorrhage (% of left ventricular mass)
timeFrame: 5±2 days after PCI
measure: Area under the curve (AUC) of creatine kinase isoenzyme (CK-MB)
timeFrame: Immediately after admission (0 hour), and 6, 12, 18, 24, 48, and 72 hours after PCI
measure: AUC of cardiac troponin I
timeFrame: Immediately after admission (0 hour), and 6, 12, 18, 24, 48, and 72 hours after PCI
measure: Peak value of CK-MB and cTnI
timeFrame: 72 hours after PCI
measure: ST segment resolution (%) according to ECG
timeFrame: 24 hours after PCI
measure: TIMI flow grade
timeFrame: Immediately after PCI
measure: Corrected TIMI frame count (CTFC)
timeFrame: Immediately after PCI
measure: TIMI myocardial perfusion grade (TMPG)
timeFrame: Immediately after PCI
measure: Myocardial salvage index
timeFrame: 5±2 days after PCI
measure: Area at risk (myocardial edema, % of left ventricular mass)
timeFrame: 5±2 days after PCI
measure: Left ventricular end-diastolic volume (LVEDV)
timeFrame: 5±2 days after PCI
measure: Left ventricular end-systolic volume (LVESV)
timeFrame: 5±2 days after PCI
measure: Left ventricular ejection fraction (LVEF)
timeFrame: 5±2 days after PCI
measure: Major adverse cardiovascular and cerebrovascular events (MACCE, including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, emergency revascularization)
timeFrame: 30 days after PCI
measure: Individual events (including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, emergency revascularization, re-hospitalization for heart failure)
timeFrame: 30 days after PCI
Other outcomes:
measure: Slow flow and no flow
timeFrame: Index procedure
measure: Malignant arrhythmia (ventricular fibrillation, ventricular tachycardia, etc.)
timeFrame: Index procedure
measure: Value of high-sensitivity C-reactive protein (Hs-CRP)
timeFrame: Immediately after admission (0 hour), and 24, 72 hours and 5 days after PCI
measure: Value of brain natriuretic peptide (BNP)
timeFrame: Immediately after admission (0 hour), and 24, 72 hours and 5 days after PCI
measure: The Myocardial Infarction Dimensional Assessment Scale (MIDAS)
timeFrame: 6 hours and 30 days after PCI
Locations:
city: Beijing
country: China
facility: Beijing Anzhen Hospital, Capital Medical University
Study officials:
References: