Randomized Evaluation of Shenfu Injection to Reduce Myocardial Injury (RESTORE)

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

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).

Study Overview

• Status: Recruiting
• Conditions: Myocardial Infarction
• Intervention / Treatment: Drug: Shenfu Injection; Drug: 5% Glucose Injection

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.

• Study Type: Interventional
• Enrollment (Anticipated): 326
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Beijing AnZhen Hospital, Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Shenfu Injection	Drug: Shenfu Injection; 80ml Shenfu Injection + 70ml 5% glucose injection, ivdrip, within 30 minutes before PCI and 1 to 5 days (once a day) after PCI (6 times in total). Drug titration time should be no less than 30 minutes.
PLACEBO_COMPARATOR: 5% Glucose Injection	Drug: 5% Glucose Injection; 150 ml 5% glucose injection, ivdrip, within 30 minutes before PCI and 1 to 5 days (once a day) after PCI (6 times in total). Drug titration time should be no less than 30 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infarct size (% of left ventricular mass)	Infarct size was assessed by performing CMR imaging at 5±2 days after PCI	5±2 days after PCI

Secondary Outcome Measures

Outcome Measure	Time Frame
Peak value of CK-MB and cTnI	72 hours after PCI
Microvascular obstruction (% of left ventricular mass)	5±2 days after PCI
Intramyocardial hemorrhage (% of left ventricular mass)	5±2 days after PCI
Area under the curve (AUC) of creatine kinase isoenzyme (CK-MB)	Immediately after admission (0 hour), and 6, 12, 18, 24, 48, and 72 hours after PCI
AUC of cardiac troponin I	Immediately after admission (0 hour), and 6, 12, 18, 24, 48, and 72 hours after PCI
ST segment resolution (%) according to ECG	24 hours after PCI
TIMI flow grade	Immediately after PCI
Corrected TIMI frame count (CTFC)	Immediately after PCI
TIMI myocardial perfusion grade (TMPG)	Immediately after PCI
Myocardial salvage index	5±2 days after PCI
Area at risk (myocardial edema, % of left ventricular mass)	5±2 days after PCI
Left ventricular end-diastolic volume (LVEDV)	5±2 days after PCI
Left ventricular end-systolic volume (LVESV)	5±2 days after PCI
Left ventricular ejection fraction (LVEF)	5±2 days after PCI
Major adverse cardiovascular and cerebrovascular events (MACCE, including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, emergency revascularization)	30 days after PCI
Individual events (including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, emergency revascularization, re-hospitalization for heart failure)	30 days after PCI

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Slow flow and no flow		Index procedure
Malignant arrhythmia (ventricular fibrillation, ventricular tachycardia, etc.)		Index procedure
Value of high-sensitivity C-reactive protein (Hs-CRP)		Immediately after admission (0 hour), and 24, 72 hours and 5 days after PCI
Value of brain natriuretic peptide (BNP)		Immediately after admission (0 hour), and 24, 72 hours and 5 days after PCI
The Myocardial Infarction Dimensional Assessment Scale (MIDAS)	0 to 140 scores, higher scores mean worse outcome	6 hours and 30 days after PCI

Collaborators and Investigators

• Sponsor: Beijing Anzhen Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 30, 2020
• Primary Completion (ANTICIPATED): July 31, 2022
• Study Completion (ANTICIPATED): August 31, 2022

Study Registration Dates

• First Submitted: July 23, 2020
• First Submitted That Met QC Criteria: July 27, 2020
• First Posted (ACTUAL): July 30, 2020

Study Record Updates

• Last Update Posted (ACTUAL): September 10, 2021
• Last Update Submitted That Met QC Criteria: September 2, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction
• Other Study ID Numbers: 2019013

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No