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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03995732
Recruitment Status : Recruiting
First Posted : June 24, 2019
Last Update Posted : September 26, 2019
Sponsor:
Collaborator:
Peking University First Hospital
Information provided by (Responsible Party):
Beijing Tide Pharmaceutical Co., Ltd

Tracking Information
First Submitted Date  ICMJE June 5, 2019
First Posted Date  ICMJE June 24, 2019
Last Update Posted Date September 26, 2019
Actual Study Start Date  ICMJE June 18, 2019
Estimated Primary Completion Date October 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 22, 2019)
  • The myocardial salvage index at 7 d after PCI [ Time Frame: 7 days ]
    The myocardial salvage index is defined as (area of myocardial edema - area of myocardial infarction)/area of myocardial edema.
  • The area of myocardial infarction at 7 d after PCI (detected by delayed-enhanced MRI [Magnetic Resonance Imaging] ) [ Time Frame: 7 days ]
    The area of myocardial infarction is defined as the percentage of left ventricular myocardium occupied by delayed enhancement.
  • Area of microvascular occlusion at 7 d after PCI [ Time Frame: 7 days ]
    Microvascular occlusion is defined as the area with no enhancement in the infarcted regions where delayed enhancement can be observed on MRI scans.
  • The area of infarction determined by the AUC (area under curve) for CK-MB (creatine kinase-muscle/brain) at 72h after PCI. [ Time Frame: 72 hours ]
    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).
  • Cardiac function at 7 d after PCI [ Time Frame: 7 days ]
    Cardiac function is assessed by assessing the left ventricular ejection fraction (percentage of stroke output to end-diastolic volume).
  • The TIMI (thrombolysis in myocardial infarction) grade of coronary blood flow after PCI. [ Time Frame: within 24 hours ]
    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.
  • The corrected TIMI frame count (cTFC) after PCI. [ Time Frame: within 24 hours ]
    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.
  • TIMI myocardial perfusion grade (TMPG) after PCI [ Time Frame: within 24 hours ]
    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.
  • Percentage of ST-segment resolution on ECG (electrocardiogram) at 90 min after PCI [ Time Frame: 90 minutes ]
    ST-resolution is defined as more than 50% of resolution.
  • Number of cardiovascular events within 30 d after PCI [ Time Frame: 30 days ]
    Cardiovascular events included all-cause death, cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization due to heart failure.
  • SOD (Superoxide Dismutase) activity [ Time Frame: 0 hours, 6 hours, 12 hours, 24 hours, 48 hours, 72 hours and 7 days after surgery ]
    Change from Baseline SOD activity at 6h, 12h, 24h, 48h, 72h and 7 d after surgery.
  • Occurence of adverse events [ Time Frame: During patient hospitalization, up to 30 days ]
    Occurence of adverse events
  • Cardiac function at 30 d after PCI [ Time Frame: 30 days ]
    Cardiac function is assessed by assessing the left ventricular ejection fraction (percentage of stroke output to end-diastolic volume).
Original Primary Outcome Measures  ICMJE
 (submitted: June 20, 2019)
  • The myocardial salvage index at 7 d after PCI [ Time Frame: 7 days ]
    The myocardial salvage index is defined as (area of myocardial edema - area of myocardial infarction)/area of myocardial edema.
  • The area of myocardial infarction at 7 d after PCI (detected by delayed-enhanced MRI [Magnetic Resonance Imaging] ) [ Time Frame: 7 days ]
    The area of myocardial infarction is defined as the percentage of left ventricular myocardium occupied by delayed enhancement.
  • Area of microvascular occlusion at 7 d after PCI [ Time Frame: 7 days ]
    Microvascular occlusion is defined as the area with no enhancement in the infarcted regions where delayed enhancement can be observed on MRI scans.
  • The area of infarction determined by the AUC (area under curve) for CK-MB (creatine kinase-muscle/brain) at 72h after PCI. [ Time Frame: 72 hours ]
    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).
  • Cardiac function at 7 d after PCI [ Time Frame: 7 days ]
    Cardiac function is assessed by assessing the left ventricular ejection fraction (percentage of stroke output to end-diastolic volume).
  • The TIMI (thrombolysis in myocardial infarction) grade of coronary blood flow after PCI. [ Time Frame: within 24 hours ]
    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.
  • The corrected TIMI frame count (cTFC) after PCI. [ Time Frame: within 24 hours ]
    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.
  • TIMI myocardial perfusion grade (TMPG) after PCI [ Time Frame: within 24 hours ]
    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.
  • Percentage of ST-segment resolution on ECG (electrocardiogram) at 90 min after PCI [ Time Frame: 90 minutes ]
    ST-resolution is defined as more than 50% of resolution.
  • Number of cardiovascular events within 30 d after PCI [ Time Frame: 30 days ]
    Cardiovascular events included all-cause death, cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization due to heart failure.
  • SOD activity [ Time Frame: 0 hours, 6 hours, 12 hours, 24 hours, 48 hours, 72 hours and 7 days after surgery ]
    Change from Baseline SOD activity at 6h, 12h, 24h, 48h, 72h and 7 d after surgery.
  • Occurence of adverse events [ Time Frame: During patient hospitalization, up to 30 days ]
    Occurence of adverse events
  • Cardiac function at 30 d after PCI [ Time Frame: 30 days ]
    Cardiac function is assessed by assessing the left ventricular ejection fraction (percentage of stroke output to end-diastolic volume).
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety Evaluation of PC-SOD for Injection in Reducing Myocardial Reperfusion Injury
Official Title  ICMJE 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
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.
Detailed 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Masking Description:

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.

Primary Purpose: Treatment
Condition  ICMJE Myocardial Reperfusion Injury
Intervention  ICMJE
  • Drug: PC-SOD
    PC-SOD will be dissolved in 10 mL of 5% glucose injection and intravenously administrated before recanalization.
  • Drug: placebo
    Placebo will be dissolved in 10 mL of 5% glucose injection and intravenously administrated before recanalization.
Study Arms  ICMJE
  • Experimental: 40 mg treatment group
    PC-SOD 40 mg dissolved in 10 mL of 5% glucose injection and intravenously administrated before recanalization.
    Intervention: Drug: PC-SOD
  • Experimental: 80 mg treatment group
    PC-SOD 80 mg dissolved in 10 mL of 5% glucose injection and intravenously administrated before recanalization.
    Intervention: Drug: PC-SOD
  • Experimental: 160 mg treatment group
    PC-SOD 160 mg dissolved in 10 mL of 5% glucose injection and intravenously administrated before recanalization.
    Intervention: Drug: PC-SOD
  • Placebo Comparator: placebo control group
    placebo dissolved in 10 mL of 5% glucose injection and intravenously administrated before recanalization.
    Intervention: Drug: placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 20, 2019)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 30, 2021
Estimated Primary Completion Date October 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Huo Yong, master 13901333060 drhuoyong@163.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03995732
Other Study ID Numbers  ICMJE CY-RD101-2
GUSU18003 ( Other Identifier: GUSU Group )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Beijing Tide Pharmaceutical Co., Ltd
Study Sponsor  ICMJE Beijing Tide Pharmaceutical Co., Ltd
Collaborators  ICMJE Peking University First Hospital
Investigators  ICMJE Not Provided
PRS Account Beijing Tide Pharmaceutical Co., Ltd
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP