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

NCT03995732 | Unknown Phase 2

• 2 other identifiers: CY-RD101-2GUSU18003
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Myocardial Reperfusion Injury

Outcome Measures

Primary Outcomes (13)

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• Occurence of adverse events

  Occurence of adverse events

  During patient hospitalization, up to 30 days

• 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

Study Arms (4)

40 mg treatment group

EXPERIMENTAL

PC-SOD 40 mg dissolved in 10 mL of 5% glucose injection and intravenously administrated before recanalization.

Drug: PC-SOD

80 mg treatment group

EXPERIMENTAL

PC-SOD 80 mg dissolved in 10 mL of 5% glucose injection and intravenously administrated before recanalization.

Drug: PC-SOD

160 mg treatment group

EXPERIMENTAL

PC-SOD 160 mg dissolved in 10 mL of 5% glucose injection and intravenously administrated before recanalization.

Drug: PC-SOD

placebo control group

PLACEBO COMPARATOR

placebo dissolved in 10 mL of 5% glucose injection and intravenously administrated before recanalization.

Drug: placebo

Interventions

PC-SOD DRUG

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

160 mg treatment group; 40 mg treatment group; 80 mg treatment group

placebo DRUG

Placebo will be dissolved in 10 mL of 5% glucose injection and intravenously administrated before recanalization.

placebo control group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 - 75 years, male or female;
• 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 );
• Killip classes I or II;
• Coronary angiography possible within 6 hours of onset;
• 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);
• Willingness to participate in the trial with ethical approval and informed consent provision.

You may not qualify if:

• Previous history of myocardial infarction;
• History of myocardial revascularization before screening;
• Thrombolytic treatment after onset;
• Cardiogenic shock;
• Cardiopulmonary resuscitation between onset and screening;
• Atrial fibrillation, atrioventricular block (degree I, II or III), and other severe arrhythmias that cannot be corrected and affect hemodynamics;
• Suspected of aortic dissection;
• Diabetes with long-term insulin use, or definite macrovascular or small vascular lesions (stroke, diabetic nephropathy, retinopathy, diabetic foot, and etc.);
• History of major surgeries within 6 months;
• History of stroke within 6 months;
• 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;
• 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;
• Allergy to two or more drugs and/or foods, or known allergy to sucrose;
• 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);
• Pregnancy or lactation in women;

Sponsors & Collaborators

• Beijing Tide Pharmaceutical Co., Ltd: lead
• Peking University First Hospital: collaborator

Study Sites (2)

Wuhan Asia Heart Hospital

Wuhan, Hubei, 430022, China

NOT YET RECRUITING

Zhongshan Hospital

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

Related Publications (8)

• Yellon DM, Hausenloy DJ. Myocardial reperfusion injury. N Engl J Med. 2007 Sep 13;357(11):1121-35. doi: 10.1056/NEJMra071667. No abstract available.

  PMID: 17855673 BACKGROUND

• 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.

  PMID: 2826476 BACKGROUND

• Werns SW, Lucchesi BR. Free radicals and ischemic tissue injury. Trends Pharmacol Sci. 1990 Apr;11(4):161-6. doi: 10.1016/0165-6147(90)90068-J.

  PMID: 2185587 BACKGROUND

• 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. doi: 10.1161/01.cir.80.5.1115.

  PMID: 2553296 BACKGROUND

• 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. doi: 10.1161/01.res.58.1.148.

  PMID: 3943152 BACKGROUND

• Engler R, Gilpin E. Can superoxide dismutase alter myocardial infarct size? Circulation. 1989 May;79(5):1137-42. doi: 10.1161/01.cir.79.5.1137. No abstract available.

  PMID: 2653661 BACKGROUND

• 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.

  PMID: 7996483 BACKGROUND

• 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. doi: 10.1136/hrt.2007.122622. Epub 2007 Dec 10.

  PMID: 18070953 BACKGROUND

MeSH Terms

Conditions

Myocardial Reperfusion Injury

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Myocardial Ischemia; Vascular Diseases; Reperfusion Injury; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Huo Yong, master

CONTACT

13901333060; drhuoyong@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Since the appearance of PC-SOD preparations cannot be identical to that of placebo, and treatment groups have different administration doses, the study will be conducted in a single-blind manner, where only subjects (and families) are blinded and do not know whether they are treated by PC-SOD or placebo before unblinding. Interpretation of cardiac MRI and ECG will also be conducted in a blinding manner. Images of all subjects will be evaluated blindly by researchers not directly involved in the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2019
• First Posted: June 24, 2019
• Study Start: June 18, 2019
• Primary Completion: October 31, 2020
• Study Completion: March 30, 2021
• Last Updated: September 26, 2019

Record last verified: 2019-09

Locations

CN (2)