Back to resultsDLBS1033 for Acute NSTEMI Without Early Coronary Revascularization
Primary Purpose
Acute Non-ST Elevation Myocardial Infarction
Status
Withdrawn
Phase
Phase 2
Locations
Indonesia
Study Type
Interventional
Intervention
DLBS1033
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Acute Non-ST Elevation Myocardial Infarction focused on measuring Acute NSTEMI, DLBS1033, SPECT, Infarct size, Left ventricular function
Eligibility Criteria
Inclusion Criteria:
- Men and women of 30-75 years of age.
Evidence of acute non-ST elevation myocardial infarction (NSTEMI) at screening, as confirmed by all of the following:
- ECG transient ST-segment deviation/depression (≥ 1 mm) or prominent T-wave inversion, in multiple precordial leads;
- Positive plasma biomarkers of myocardial necrosis: cardiac troponin I (cTnI);
- Clinical symptoms of chest discomfort/pain or anginal equivalent (dyspnea, diaphoresis, excessive vomiting in diabetic patients and arm or jaw pain).
- High risk subjects, defined as having Thrombolysis in Myocardial Infarction (TIMI) score ≥ 4
- Subjects refuse to undergo reperfusion therapies, such as coronary artery-bypass surgery (CABG) or percutaneous coronary intervention (PCI) within the next six months.
- Therapy with study medication can be started within 7 days after first presentation in the hospital.
- Able to take oral medication.
Exclusion Criteria:
- For females of childbearing potential: pregnancy, breast-feeding, the intention of becoming pregnant.
- ECG presentation of STEMI.
- History of hemorrhagic stroke within the last 3 months.
- Patients with seizure at the onset of stroke or with regular medication for seizure/epilepsy.
- History of serious head injury within the last 3 months.
- History of major surgery within the last 3 months.
- Ongoing long term need for oral anticoagulants, antiplatelets, fibrinolytic, or antithrombotic agents, other than the study medication.
- Having any implanted pacemaker or cardiac resynchronization therapy (CRT) or cardiac resynchronization therapy defibrillators (CRT-D).
- Clinically significant arrhythmias or atrioventricular conduction block greater than first degree.
- Acute or chronic heart failure as defined by the New York Heart Association (NYHA) classification as functional Class IV.
- Known severe LV dysfunction (EF ≤ 40 and EDD > 55 mm).
- Inadequate liver function: ALT > 3 times upper limit of normal (ULN).
- Inadequate renal function: serum creatinine ≥ 1.5 times upper limit of normal (ULN).
- Uncontrolled hypertension (SBP > 185 mmHg or DBP > 110 mmHg).
- Random plasma glucose ≥ 180 mg/dL and HbA1c ≥ 7.0% at Screening.
- Moderate to high risk of bleeding, defined as those who have the CRUSADE bleeding score of > 30.
- Known or suspected allergy to any of study medications used in the study, including other lumbrokinase products.
- Prior experience with DLBS1033 or other oral lumbrokinase products.
- Clinical evidence of malignancies with survival period < 1 year.
- Any other disease which judged by the investigator could interfere with trial participation or trial evaluation.
- Enrolled in other interventional protocol within 30 days prior to Screening.
Sites / Locations
- Central Army Hospital RSPAD Gatot Soebroto
- Binawaluya Cardiac Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
DLBS1033
Placebo
Arm Description
DLBS1033 enteric-coated tablet is administered at the dose of 490 mg, one tablet three times daily, everyday for eight weeks of study period
Placebo is administered one tablet three times daily, everyday for eight weeks of study period
Outcomes
Primary Outcome Measures
Infarct size
The quantitative change of infarct size, measured using SPECT.
Secondary Outcome Measures
LV function
Improvement in left ventricular (LV) function, measured by 2D echocardiography.
Composite endpoints
Composite endpoints (composite of major adverse cardiovascular events), comprising of all-cause of death, recurrent myocardial infarction or ischemic stroke within the study period.
Individual event of MACE and other cardiovascular events
Individual event of MACE and other cardiovascular events, such as: shock, pulmonary oedema, congestive heart failure, arrhythmias, hemodynamic instability/cardiogenic shock, including the presence of new infarct(s) within the study period.
Nitroglycerin amount
Number of nitroglycerin (rescue medicine) taken during the study period.
Plasma fibrinogen level
Change in plasma fibrinogen level.
Plasma d-dimer level
Change in plasma d-dimer level.
hs-CRP
Change in hs-CRP.
Routine hematology
Routine hematology measured includes: hemoglobin, hematocrit, RBC, WBC, differentiation of WBC, and platelet count. Particularly for hemoglobin and hematocrit level, they are measured at baseline and every interval of 2 weeks over the first 8 weeks of treatment and at the end of study (week 24).
Liver function
Liver function measured includes: serum ALT (SGPT), serum AST (SGOT), alkaline phosphatase, and total bilirubin. Particularly for serum ALT, it is measured at baseline and every interval of 2 weeks over the first 8 weeks of treatment and at the end of study (week 24).
Renal function
Renal function measured includes: serum creatinine and BUN. Particularly for serum creatinine, it is measured at baseline and every interval of 2 weeks over the first 8 weeks of treatment and at the end of study (week 24).
Haemostasis parameter
Haemostasis parameter measured includes: prothrombin time (PT), International Normalized Ratio (INR), and activated partial thromboplastin time (aPTT). Particularly for PT and INR, they are measured at baseline and every interval of 2 weeks over the first 8 weeks of treatment and at the end of study (week 24).
Adverse event
Adverse events (especially major and minor bleeding) are observed and carefully evaluated along the course of the study.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02146664
Brief Title
DLBS1033 for Acute NSTEMI Without Early Coronary Revascularization
Official Title
The Role of DLBS1033 in The Management of Acute Non-ST Elevation of Myocardial Infarction (NSTEMI) Without Early Coronary Revascularization
Study Type
Interventional
2. Study Status
Record Verification Date
April 2016
Overall Recruitment Status
Withdrawn
Why Stopped
The investigational cases were no longer relevant considering the recent implementation of our current national healthcare system.
Study Start Date
November 2015 (undefined)
Primary Completion Date
November 2017 (Anticipated)
Study Completion Date
March 2018 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Dexa Medica Group
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a prospective, randomized, double-blind, double-dummy, and controlled study of DLBS1033 in the management of acute non-ST elevation myocardial infarction (NSTEMI) without early coronary revascularization. It is hypothesized that the combination of DLBS1033 with aspirin and clopidogrel will result in greater reduction of infarct size in comparison with that of aspirin and clopidogrel alone.
Detailed Description
After diagnosed NSTEMI, patient is hospitalized and given medications according to the standard management of acute NSTEMI, including anticoagulant low molecular weight heparin. Eligible subjects are then randomized to receive either DLBS1033 at a dose of 490 mg three times daily or its placebo in addition to clopidogrel 75 mg once daily and aspirin 160 mg once daily for an 8-week course of therapy. Afterwards, the administration of DLBS1033 and its placebo are stopped, while the dual antiplatelet therapy (aspirin and clopidogrel) remains for another 16 weeks at the same dose regimen as the previous.
Clinical and laboratory examinations to evaluate the investigational drug's efficacy and safety are performed at baseline, week 4, week 8, and week 24. To guard the safety of the study subjects, haemostasis parameters, hematology parameters, and CRUSADE bleeding score are evaluated every two-week-interval over the first eight weeks of treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Non-ST Elevation Myocardial Infarction
Keywords
Acute NSTEMI, DLBS1033, SPECT, Infarct size, Left ventricular function
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
DLBS1033
Arm Type
Experimental
Arm Description
DLBS1033 enteric-coated tablet is administered at the dose of 490 mg, one tablet three times daily, everyday for eight weeks of study period
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo is administered one tablet three times daily, everyday for eight weeks of study period
Intervention Type
Drug
Intervention Name(s)
DLBS1033
Other Intervention Name(s)
Disolf
Intervention Description
Investigational drug or placebo will be given in addition to the standard therapy which consists of: aspirin enteric-coated tablet 1 x 160 mg (two tablets @ 80 mg) and clopidogrel film-coated tablet 1 x 75 mg daily for eight weeks. Standard therapy alone will still be given afterwards, for another sixteen weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Investigational drug or placebo will be given in addition to the standard therapy which consists of: aspirin enteric-coated tablet 1 x 160 mg (two tablets @ 80 mg) and clopidogrel film-coated tablet 1 x 75 mg daily for eight weeks. Standard therapy alone will still be given afterwards, for another sixteen weeks
Primary Outcome Measure Information:
Title
Infarct size
Description
The quantitative change of infarct size, measured using SPECT.
Time Frame
Week 0, week 8, week 24
Secondary Outcome Measure Information:
Title
LV function
Description
Improvement in left ventricular (LV) function, measured by 2D echocardiography.
Time Frame
Week 0, week 4, week 8, and week 24
Title
Composite endpoints
Description
Composite endpoints (composite of major adverse cardiovascular events), comprising of all-cause of death, recurrent myocardial infarction or ischemic stroke within the study period.
Time Frame
Week 0 - 24
Title
Individual event of MACE and other cardiovascular events
Description
Individual event of MACE and other cardiovascular events, such as: shock, pulmonary oedema, congestive heart failure, arrhythmias, hemodynamic instability/cardiogenic shock, including the presence of new infarct(s) within the study period.
Time Frame
Week 0 - 24
Title
Nitroglycerin amount
Description
Number of nitroglycerin (rescue medicine) taken during the study period.
Time Frame
Week 0 - 24
Title
Plasma fibrinogen level
Description
Change in plasma fibrinogen level.
Time Frame
Week 0, 4, 8, and 24
Title
Plasma d-dimer level
Description
Change in plasma d-dimer level.
Time Frame
Week 0, 4, 8, and 24
Title
hs-CRP
Description
Change in hs-CRP.
Time Frame
Week 0, 4, 8, and 24
Title
Routine hematology
Description
Routine hematology measured includes: hemoglobin, hematocrit, RBC, WBC, differentiation of WBC, and platelet count. Particularly for hemoglobin and hematocrit level, they are measured at baseline and every interval of 2 weeks over the first 8 weeks of treatment and at the end of study (week 24).
Time Frame
Week 0, 4, 8, and 24
Title
Liver function
Description
Liver function measured includes: serum ALT (SGPT), serum AST (SGOT), alkaline phosphatase, and total bilirubin. Particularly for serum ALT, it is measured at baseline and every interval of 2 weeks over the first 8 weeks of treatment and at the end of study (week 24).
Time Frame
Week 0, 4, 8, and 24
Title
Renal function
Description
Renal function measured includes: serum creatinine and BUN. Particularly for serum creatinine, it is measured at baseline and every interval of 2 weeks over the first 8 weeks of treatment and at the end of study (week 24).
Time Frame
Week 0, 4, 8, and 24
Title
Haemostasis parameter
Description
Haemostasis parameter measured includes: prothrombin time (PT), International Normalized Ratio (INR), and activated partial thromboplastin time (aPTT). Particularly for PT and INR, they are measured at baseline and every interval of 2 weeks over the first 8 weeks of treatment and at the end of study (week 24).
Time Frame
Week 0, 4, 8, and 24
Title
Adverse event
Description
Adverse events (especially major and minor bleeding) are observed and carefully evaluated along the course of the study.
Time Frame
Week 0 - 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Men and women of 30-75 years of age.
Evidence of acute non-ST elevation myocardial infarction (NSTEMI) at screening, as confirmed by all of the following:
ECG transient ST-segment deviation/depression (≥ 1 mm) or prominent T-wave inversion, in multiple precordial leads;
Positive plasma biomarkers of myocardial necrosis: cardiac troponin I (cTnI);
Clinical symptoms of chest discomfort/pain or anginal equivalent (dyspnea, diaphoresis, excessive vomiting in diabetic patients and arm or jaw pain).
High risk subjects, defined as having Thrombolysis in Myocardial Infarction (TIMI) score ≥ 4
Subjects refuse to undergo reperfusion therapies, such as coronary artery-bypass surgery (CABG) or percutaneous coronary intervention (PCI) within the next six months.
Therapy with study medication can be started within 7 days after first presentation in the hospital.
Able to take oral medication.
Exclusion Criteria:
For females of childbearing potential: pregnancy, breast-feeding, the intention of becoming pregnant.
ECG presentation of STEMI.
History of hemorrhagic stroke within the last 3 months.
Patients with seizure at the onset of stroke or with regular medication for seizure/epilepsy.
History of serious head injury within the last 3 months.
History of major surgery within the last 3 months.
Ongoing long term need for oral anticoagulants, antiplatelets, fibrinolytic, or antithrombotic agents, other than the study medication.
Having any implanted pacemaker or cardiac resynchronization therapy (CRT) or cardiac resynchronization therapy defibrillators (CRT-D).
Clinically significant arrhythmias or atrioventricular conduction block greater than first degree.
Acute or chronic heart failure as defined by the New York Heart Association (NYHA) classification as functional Class IV.
Known severe LV dysfunction (EF ≤ 40 and EDD > 55 mm).
Inadequate liver function: ALT > 3 times upper limit of normal (ULN).
Inadequate renal function: serum creatinine ≥ 1.5 times upper limit of normal (ULN).
Uncontrolled hypertension (SBP > 185 mmHg or DBP > 110 mmHg).
Random plasma glucose ≥ 180 mg/dL and HbA1c ≥ 7.0% at Screening.
Moderate to high risk of bleeding, defined as those who have the CRUSADE bleeding score of > 30.
Known or suspected allergy to any of study medications used in the study, including other lumbrokinase products.
Prior experience with DLBS1033 or other oral lumbrokinase products.
Clinical evidence of malignancies with survival period < 1 year.
Any other disease which judged by the investigator could interfere with trial participation or trial evaluation.
Enrolled in other interventional protocol within 30 days prior to Screening.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Muhammad Munawar, SpJP(K), MD
Organizational Affiliation
Binawaluya Cardiac Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ismi Purnawan, SpJP(K), MD
Organizational Affiliation
Central Army Hospital RSPAD Gatot Soebroto
Official's Role
Principal Investigator
Facility Information:
Facility Name
Central Army Hospital RSPAD Gatot Soebroto
City
Central Jakarta
State/Province
Jakarta
Country
Indonesia
Facility Name
Binawaluya Cardiac Hospital
City
Jakarta
ZIP/Postal Code
13570
Country
Indonesia
12. IPD Sharing Statement
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DLBS1033 for Acute NSTEMI Without Early Coronary Revascularization
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