Randomized Evaluation of Shenfu Injection to Reduce Myocardial Injury

Myocardial Infarction Clinical Trial

— RESTORE  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04493840
• Other study ID #: 2019013
• Status: Recruiting
• Phase: Phase 4
• Start date: July 30, 2020
• Est. completion date: August 31, 2022

Study information

• Verified date: September 2021
• Source: Beijing Anzhen Hospital
• Contact: Shao-Ping Nie, MD, PhD
• Phone: 86-10-84005256
• Email: spnie[@]ccmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 326
• Est. completion date: August 31, 2022
• Est. primary completion date: July 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction

Intervention

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.
• 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.

Locations

Country	Name	City	State
China	Beijing Anzhen Hospital, Capital Medical University	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Anzhen Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Slow flow and no flow		Index procedure
Other	Malignant arrhythmia (ventricular fibrillation, ventricular tachycardia, etc.)		Index procedure
Other	Value of high-sensitivity C-reactive protein (Hs-CRP)		Immediately after admission (0 hour), and 24, 72 hours and 5 days after PCI
Other	Value of brain natriuretic peptide (BNP)		Immediately after admission (0 hour), and 24, 72 hours and 5 days after PCI
Other	The Myocardial Infarction Dimensional Assessment Scale (MIDAS)	0 to 140 scores, higher scores mean worse outcome	6 hours and 30 days after PCI
Primary	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	Microvascular obstruction (% of left ventricular mass)		5±2 days after PCI
Secondary	Intramyocardial hemorrhage (% of left ventricular mass)		5±2 days after PCI
Secondary	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
Secondary	AUC of cardiac troponin I		Immediately after admission (0 hour), and 6, 12, 18, 24, 48, and 72 hours after PCI
Secondary	Peak value of CK-MB and cTnI		72 hours after PCI
Secondary	ST segment resolution (%) according to ECG		24 hours after PCI
Secondary	TIMI flow grade		Immediately after PCI
Secondary	Corrected TIMI frame count (CTFC)		Immediately after PCI
Secondary	TIMI myocardial perfusion grade (TMPG)		Immediately after PCI
Secondary	Myocardial salvage index		5±2 days after PCI
Secondary	Area at risk (myocardial edema, % of left ventricular mass)		5±2 days after PCI
Secondary	Left ventricular end-diastolic volume (LVEDV)		5±2 days after PCI
Secondary	Left ventricular end-systolic volume (LVESV)		5±2 days after PCI
Secondary	Left ventricular ejection fraction (LVEF)		5±2 days after PCI
Secondary	Major adverse cardiovascular and cerebrovascular events (MACCE, including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, emergency revascularization)		30 days after PCI
Secondary	Individual events (including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, emergency revascularization, re-hospitalization for heart failure)		30 days after PCI