Clinical trial NCT02146664: 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
Overall status: WITHDRAWN
Phase: PHASE2
PHASE3
Conditions: Acute Non-ST Elevation Myocardial Infarction
Keywords: Acute NSTEMI
DLBS1033
SPECT
Infarct size
Left ventricular function
Lead sponsor: Dexa Medica Group
Sponsor class: INDUSTRY
First posted: 2014-05-26
Enrollment: 0
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Infarct size
timeFrame: Week 0, week 8, week 24
Secondary outcomes:
measure: LV function
timeFrame: Week 0, week 4, week 8, and week 24
measure: Composite endpoints
timeFrame: Week 0 - 24
measure: Individual event of MACE and other cardiovascular events
timeFrame: Week 0 - 24
measure: Nitroglycerin amount
timeFrame: Week 0 - 24
measure: Plasma fibrinogen level
timeFrame: Week 0, 4, 8, and 24
measure: Plasma d-dimer level
timeFrame: Week 0, 4, 8, and 24
measure: hs-CRP
timeFrame: Week 0, 4, 8, and 24
measure: Routine hematology
timeFrame: Week 0, 4, 8, and 24
measure: Liver function
timeFrame: Week 0, 4, 8, and 24
measure: Renal function
timeFrame: Week 0, 4, 8, and 24
measure: Haemostasis parameter
timeFrame: Week 0, 4, 8, and 24
measure: Adverse event
timeFrame: Week 0 - 24
Other outcomes:
Locations:
city: Central Jakarta
country: Indonesia
facility: Central Army Hospital RSPAD Gatot Soebroto
state: Jakarta
city: Jakarta
country: Indonesia
facility: Binawaluya Cardiac Hospital
Study officials:
affiliation: Binawaluya Cardiac Hospital
name: Muhammad Munawar, SpJP(K), MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Central Army Hospital RSPAD Gatot Soebroto
name: Ismi Purnawan, SpJP(K), MD
role: PRINCIPAL_INVESTIGATOR
References: