DLBS1033 for Acute NSTEMI Without Early Coronary Revascularization

The Role of DLBS1033 in The Management of Acute Non-ST Elevation of Myocardial Infarction (NSTEMI) Without Early Coronary Revascularization

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.

Study Overview

• Status: Withdrawn
• Conditions: Acute Non-ST Elevation Myocardial Infarction
• Intervention / Treatment: Drug: DLBS1033; Drug: Placebo

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.

• Study Type: Interventional
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Indonesia
  • Jakarta, Indonesia, 13570
    • Binawaluya Cardiac Hospital
  • Jakarta
    • Central Jakarta, Jakarta, Indonesia
      • Central Army Hospital RSPAD Gatot Soebroto

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DLBS1033; DLBS1033 enteric-coated tablet is administered at the dose of 490 mg, one tablet three times daily, everyday for eight weeks of study period	Drug: DLBS1033; 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; Other Names: Disolf
Placebo Comparator: Placebo; Placebo is administered one tablet three times daily, everyday for eight weeks of study period	Drug: Placebo; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infarct size	The quantitative change of infarct size, measured using SPECT.	Week 0, week 8, week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LV function	Improvement in left ventricular (LV) function, measured by 2D echocardiography.	Week 0, week 4, week 8, and week 24
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.	Week 0 - 24
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.	Week 0 - 24
Nitroglycerin amount	Number of nitroglycerin (rescue medicine) taken during the study period.	Week 0 - 24
Plasma fibrinogen level	Change in plasma fibrinogen level.	Week 0, 4, 8, and 24
Plasma d-dimer level	Change in plasma d-dimer level.	Week 0, 4, 8, and 24
hs-CRP	Change in hs-CRP.	Week 0, 4, 8, and 24
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).	Week 0, 4, 8, and 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).	Week 0, 4, 8, and 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).	Week 0, 4, 8, and 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).	Week 0, 4, 8, and 24
Adverse event	Adverse events (especially major and minor bleeding) are observed and carefully evaluated along the course of the study.	Week 0 - 24

Collaborators and Investigators

• Sponsor: Dexa Medica Group
• Investigators: Principal Investigator: Ismi Purnawan, SpJP(K), MD, Central Army Hospital RSPAD Gatot Soebroto

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Anticipated): November 1, 2017
• Study Completion (Anticipated): March 1, 2018

Study Registration Dates

• First Submitted: May 13, 2014
• First Submitted That Met QC Criteria: May 21, 2014
• First Posted (Estimate): May 26, 2014

Study Record Updates

• Last Update Posted (Estimate): April 20, 2016
• Last Update Submitted That Met QC Criteria: April 18, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: SPECT; Infarct size; Left ventricular function; DLBS1033; Acute NSTEMI
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Non-ST Elevated Myocardial Infarction
• Other Study ID Numbers: DLBS1033-0513