Efficacy and Safety Evaluation of PC-SOD for Injection in Reducing Myocardial Reperfusion Injury

Myocardial Reperfusion Injury Clinical Trial

Official title:

Efficacy and Safety Evaluation of Phosphatidyl Choline Cu/Zn Superoxide Dismutase (PC-SOD) for Injection in Reducing Myocardial Reperfusion Injury: a Multicenter, Randomized, Single-blind, Placebo-controlled Dose-finding Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03995732
• Other study ID #: CY-RD101-2
• Secondary ID: GUSU18003
• Status: Recruiting
• Phase: Phase 2
• Start date: June 18, 2019
• Est. completion date: March 30, 2021

Study information

• Verified date: September 2019
• Source: Beijing Tide Pharmaceutical Co., Ltd
• Contact: Huo Yong, master
• Phone: 13901333060
• Email: drhuoyong[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The current study aims to evaluate different doses of PC-SOD injections for efficacy and safety in comparison to placebo, in order to provide a basis for future clinical trials in terms of experimental design and dose selection.

Description:

The study is a randomized, single-blind, multi-center, placebo-controlled trial to preliminarily evaluate the efficacy and safety of PC-SOD, and to provide a basis for dose selection in the next stage of study.

For each participant, the trial will be divided into the screening/treatment (screening and treatment conducted during the first visit, 0 d) and safety follow-up (1 - 30 d) stages.

The study will screen 120 eligible subjects. After successful screening, the subjects will be randomly assigned into four groups of equal size, including the 40 mg PC-SOD, 80 mg PC-SOD, 160 mg PC-SOD and placebo control groups. Subjects in each group will be administered the corresponding intervention, followed by PCI treatment. During the safety follow-up stage, the subjects will receive basic treatment based on Guidelines for Management of Patients with ST-segment elevation myocardial infarction. Treatments will include dual anti-platelet therapy, beta-blockers, ACEI/ARB (angiotensin-converting enzyme inhibitor/ angiotensin receptor blocker), statins, anticoagulants, and so on.

By comparing the efficacy and safety endpoints of patients in the experimental and placebo control groups, the study aims to preliminarily evaluate the efficacy and safety of different doses of PC-SOD in reducing myocardial reperfusion injury.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: March 30, 2021
• Est. primary completion date: October 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Age 18 - 75 years, male or female;

2. Meeting the diagnostic criteria of AMI (chest pain for over 10 - 20 min, which could not be relieved completely by oral nitroglycerin; ST elevation = 2 mm in two or more adjacent leads in leads V1-V5 );

3. Killip classes I or II;

4. Coronary angiography possible within 6 hours of onset;

5. Emergent coronary angiography showing occlusion in left anterior descending artery (TIMI grade 0 - 1); patients with this symptom could also be included despite inconformity to criterion 2);

6. Willingness to participate in the trial with ethical approval and informed consent provision.

Exclusion Criteria:

General exclusion criteria

1. Previous history of myocardial infarction;

2. History of myocardial revascularization before screening;

3. Thrombolytic treatment after onset;

4. Cardiogenic shock;

5. Cardiopulmonary resuscitation between onset and screening;

6. Atrial fibrillation, atrioventricular block (degree I, II or III), and other severe arrhythmias that cannot be corrected and affect hemodynamics;

7. Suspected of aortic dissection;

8. Diabetes with long-term insulin use, or definite macrovascular or small vascular lesions (stroke, diabetic nephropathy, retinopathy, diabetic foot, and etc.);

9. History of major surgeries within 6 months;

10. History of stroke within 6 months;

11. History of immune disorders within 6 months (such as cancer, lymphoma, HIV or hepatitis), or use of immunosuppressive agents at doses that can cause immunosuppression within 10 days;

12. Clinically significant diseases of the respiratory, digestive, blood, immune, endocrine, nervous or urinary systems (renal insufficiency in particular), and diseases that might cause serious risk to patients based on the judgement of researchers;

13. Allergy to two or more drugs and/or foods, or known allergy to sucrose;

14. Any contraindications for cardiac MRI, such as implantation of metal objects (pacemakers and/or implantable defibrillators; insulin pumps, or any other electronic devices; cerebral clips, aneurysm clips, and etc.), and other contraindications (such as claustrophobia);

15. Pregnancy or lactation in women;

16. Participation in other clinical trials within 3 months;

17. Situations considered unsuitable for enrollment (such as disease condition or patient compliance).

Exclusion criteria for angiography

1. Occlusion of left main artery;

2. Apart from the left anterior descending branch, other blood vessels requiring revascularization in the same period or within a month.

Related Conditions & MeSH terms

• Myocardial Reperfusion Injury
• Reperfusion Injury
• Wounds and Injuries

Intervention

Drug:
• PC-SOD
PC-SOD will be dissolved in 10 mL of 5% glucose injection and intravenously administrated before recanalization.
• placebo
Placebo will be dissolved in 10 mL of 5% glucose injection and intravenously administrated before recanalization.

Locations

Country	Name	City	State
China	Zhongshan Hospital	Shanghai	Shanghai
China	Wuhan Asia Heart Hospital	Wuhan	Hubei

Sponsors (2)

Lead Sponsor	Collaborator
Beijing Tide Pharmaceutical Co., Ltd	Peking University First Hospital

Country where clinical trial is conducted

China, 

References & Publications (8)

Engler R, Gilpin E. Can superoxide dismutase alter myocardial infarct size? Circulation. 1989 May;79(5):1137-42. Review. — View Citation

Igarashi R, Hoshino J, Ochiai A, Morizawa Y, Mizushima Y. Lecithinized superoxide dismutase enhances its pharmacologic potency by increasing its cell membrane affinity. J Pharmacol Exp Ther. 1994 Dec;271(3):1672-7. — View Citation

Kloner RA, Przyklenk K, Whittaker P. Deleterious effects of oxygen radicals in ischemia/reperfusion. Resolved and unresolved issues. Circulation. 1989 Nov;80(5):1115-27. Review. — View Citation

Przyklenk K, Kloner RA. Superoxide dismutase plus catalase improve contractile function in the canine model of the "stunned myocardium". Circ Res. 1986 Jan;58(1):148-56. — View Citation

Werns SW, Lucchesi BR. Free radicals and ischemic tissue injury. Trends Pharmacol Sci. 1990 Apr;11(4):161-6. Review. — View Citation

Wu E, Ortiz JT, Tejedor P, Lee DC, Bucciarelli-Ducci C, Kansal P, Carr JC, Holly TA, Lloyd-Jones D, Klocke FJ, Bonow RO. Infarct size by contrast enhanced cardiac magnetic resonance is a stronger predictor of outcomes than left ventricular ejection fraction or end-systolic volume index: prospective cohort study. Heart. 2008 Jun;94(6):730-6. Epub 2007 Dec 10. — View Citation

Yellon DM, Hausenloy DJ. Myocardial reperfusion injury. N Engl J Med. 2007 Sep 13;357(11):1121-35. Review. — View Citation

Zweier JL. Measurement of superoxide-derived free radicals in the reperfused heart. Evidence for a free radical mechanism of reperfusion injury. J Biol Chem. 1988 Jan 25;263(3):1353-7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The myocardial salvage index at 7 d after PCI	The myocardial salvage index is defined as (area of myocardial edema - area of myocardial infarction)/area of myocardial edema.	7 days
Primary	The area of myocardial infarction at 7 d after PCI (detected by delayed-enhanced MRI [Magnetic Resonance Imaging] )	The area of myocardial infarction is defined as the percentage of left ventricular myocardium occupied by delayed enhancement.	7 days
Primary	Area of microvascular occlusion at 7 d after PCI	Microvascular occlusion is defined as the area with no enhancement in the infarcted regions where delayed enhancement can be observed on MRI scans.	7 days
Primary	The area of infarction determined by the AUC (area under curve) for CK-MB (creatine kinase-muscle/brain) at 72h after PCI.	The area of infarction at 72h after surgery will be roughly estimated by calculating the AUC for CK-MB (before operation, and at 6, 12, 24, 48 and 72h after operation, respectively).	72 hours
Primary	Cardiac function at 7 d after PCI	Cardiac function is assessed by assessing the left ventricular ejection fraction (percentage of stroke output to end-diastolic volume).	7 days
Primary	The TIMI (thrombolysis in myocardial infarction) grade of coronary blood flow after PCI.	Coronary artery reperfusion will be assessed by the TIMI grading system, whose grades include: Grade 0: no contrast filling at the occlusion site and distal end; Grade 1: the contrast passes some of the occluded sites, but cannot fill the distal vessels; Grade 2: the contrast can fill the distal end of coronary artery completely, but the filling and clearing of contrast is slower than that of normal coronary artery; Grade 3: the contrast can fill the distal end rapidly and completely, and can be removed quickly.; The TIMI flow grades will be determined by two physicians separately. In case of disagreement, a lead physician will help make the final call.	within 24 hours
Primary	The corrected TIMI frame count (cTFC) after PCI.	The left anterior descending (LAD) artery will be analyzed in a 30º right anterior oblique view with 30º cranial angulation. The left circumflex (LCX) will be analyzed in a 30º right anterior oblique view with 30º caudal angulation. The right coronary artery (RCA) will be analyzed in a 45º left anterior oblique view.	within 24 hours
Primary	TIMI myocardial perfusion grade (TMPG) after PCI	Grade 0: no contrast entering the myocardium; Grade 1: the contrast enters myocardium slowly, with myocardial staining not disappearing or lasting for more than 30 s in the targeted vessels; Grade 2: delayed entering and disappearing of contrast in the myocardium, exceeding 3 cardiac cycles; Grade 3: normal entering and disappearing of contrast in the myocardium, occurring within 3 cardiac cycles.	within 24 hours
Primary	Percentage of ST-segment resolution on ECG (electrocardiogram) at 90 min after PCI	ST-resolution is defined as more than 50% of resolution.	90 minutes
Primary	Number of cardiovascular events within 30 d after PCI	Cardiovascular events included all-cause death, cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization due to heart failure.	30 days
Primary	SOD (Superoxide Dismutase) activity	Change from Baseline SOD activity at 6h, 12h, 24h, 48h, 72h and 7 d after surgery.	0 hours, 6 hours, 12 hours, 24 hours, 48 hours, 72 hours and 7 days after surgery
Primary	Occurence of adverse events	Occurence of adverse events	During patient hospitalization, up to 30 days
Primary	Cardiac function at 30 d after PCI	Cardiac function is assessed by assessing the left ventricular ejection fraction (percentage of stroke output to end-diastolic volume).	30 days