A Trial Using Double-Bolus THR-100 Versus Streptokinase

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bharat Biotech International Limited
ClinicalTrials.gov Identifier:
NCT01305226
First received: December 28, 2010
Last updated: February 2, 2012
Last verified: February 2012
  Purpose

This novel fibrinolytic agent is a 136 amino acid single chain protein secreted by some strains of Staphylococcus aureus and readily produced by recombinant DNA technology. Two natural variants of recombinant staphylokinase, THR-100 and SakSTAR, have been developed for investigational use in preliminary trials. Like SK, it forms an equimolar complex with plasmin which in turn activates plasminogen to plasmin. Unlike SK, the complexed, activated molecule (which undergoes proteolytic cleavage of the first ten amino acids to generate active staphylokinase) has a high degree of fibrin-selectivity in a human plasma milieu. This fibrin-selectivity is due in large measure to potent activation at the clot surface by trace amounts of plasmin, and rapid inactivation of the circulating complex by antiplasmin. Hence, it provides an interesting and promising alternative therapy.


Condition Intervention Phase
Acute Myocardial Infarction
Drug: THR-100
Drug: Streptokinase
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective Phase III Parallel, Randomised Controlled Trial Using Double-bolus Recombinant Staphylokinase (THR-100) vs Streptokinase in Patients With Acute Myocardial Infarction

Resource links provided by NLM:


Further study details as provided by Bharat Biotech International Limited:

Primary Outcome Measures:
  • To demonstrate efficacy of THR100 as compared with streptokinase by assessment of 12-lead Electrocardiogram, specific cardiac Enzymes levels, pain relief and TIMI-90. (Non-Inferiority study) [ Time Frame: up to 4 weeks ] [ Designated as safety issue: Yes ]
    12-lead Electrocardiogram, ≥50% resolution of ST segment in single ECG lead of maximum deviation present at 90 minutes and 24 hours after start of thrombolytic therapy.


Secondary Outcome Measures:
  • To evaluate the safety profile of THR-100 in comparison with Streptokinase [ Time Frame: up to 4 weeks ] [ Designated as safety issue: Yes ]
    Assessment of net clinical benefit, defined as reduced mortality, non-fatal stroke, clinically-evident intracranial hemorrhage, or recurrent myocardial infarction at thirty (30) days.


Enrollment: 120
Study Start Date: October 2010
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Test - THR-100
120 subjects are to be recruited into the trial, with patients randomized in a 1:1 allocation ratio to THR-100 and Streptokinase 60 subjects are to be recruited into Test arm, and administered 15 mg double-bolus (15mg/15ml), separated by 30 minutes (total 30 mg)
Drug: THR-100
THR-100: 15 mg double-bolus (15mg/15ml), separated by 30 minutes (total 30 mg)
Other Name: Staphylokinase
Active Comparator: Streptokinase
120 subjects are to be recruited into the trial, with patients randomized in a 1:1 allocation ratio to THR-100 and Streptokinase Streptokinase: Standard regimen (1.5 million IU) is made up in 150 ml of physiological saline or glucose solution and administered intravenously over a period of 60 minutes.
Drug: Streptokinase
Streptokinase: Standard regimen (1.5 million IU) is made up in 150 ml of physiological saline or glucose solution and administered intravenously over a period of 60 minutes.
Other Name: Streptase

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   30 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patients aged 30 to < 75 years inclusive.
  2. Patients presenting within 12 hours with symptoms presumed secondary to an acute myocardial infarction lasting at least 20 minutes and accompanied by ECG evidence of > 1mm of ST elevation in 2 or more limb leads or > 2mm in 2 or more contiguous precordial leads or suspected new left bundle branch block will be eligible.
  3. Patients must be in the hospital or the emergency department and able to receive the study medication within 12 hours of onset of symptoms.
  4. Females of child-bearing age, not using a generally accepted method of contraception must have a negative urine pregnancy test.
  5. Written informed consent should be sought from the patient prior to inclusion in the study. If unable to do so, informed verbal consent will be obtained. If neither is possible, a legally acceptable representative (relative) should provide written consent.
  6. NB Verbal or written consent should be followed by written informed consent from the patient at the earliest subsequent opportunity.

Exclusion Criteria:

  1. Previous administration of staphylokinase.
  2. Active bleeding or known hemorrhagic diathesis.
  3. Any history of stroke, transient ischemic attack, dementia, or structural CNS damage e.g. neoplasm, aneurysm, AV malformation.
  4. Major surgery or trauma within the past 3 months.
  5. Significant hypertension i.e. SBP 180 mm Hg and/or DBP 110 mm Hg at any time from admission to randomization.
  6. Current treatment with vitamin K antagonists resulting with an INR > 1.5.
  7. Anticipated difficulty with vascular access.
  8. Prolonged (>10 min) cardiopulmonary resuscitation or cardiogenic shock.
  9. Patients who have participated in an investigational drug study within the past 30 days.
  10. Pregnancy or lactation, parturition within the previous 30 days.
  11. Any serious concomitant systemic or life limiting disorder that would be incompatible with the trial
  12. Patients known to have a history of or life limiting malignant disease or HIV.
  13. Significant hepatic or renal dysfunction or any other condition which, in the opinion of the Investigator, makes the patient unsuitable for study entry.
  14. Previous participation in this trial
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01305226

Locations
India
Sri Jayadeva Institute of Cardiology.
Bangalore, Karnataka, India, 560 069
Narayana Hrudayalaya
Bangalore, Karnataka, India, 560 099
Lotus Super speciality Hospita
Agra, Uttar Pradesh, India, 282 002
Institute of Post Graduate Medical Education and Research (IPGMER)
Kolkatta, West Bengal, India, 700 020
Sponsors and Collaborators
Bharat Biotech International Limited
Investigators
Study Director: Dr.A Singh, MBBS, MD Bharat Biotech Int. Ltd.
  More Information

No publications provided

Responsible Party: Bharat Biotech International Limited
ClinicalTrials.gov Identifier: NCT01305226     History of Changes
Other Study ID Numbers: BBIL/STA/05/2007
Study First Received: December 28, 2010
Last Updated: February 2, 2012
Health Authority: India: Drugs Controller General of India
India: Ministry of Health
United States: Food and Drug Administration

Keywords provided by Bharat Biotech International Limited:
THR 100

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Streptokinase
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Hematologic Agents

ClinicalTrials.gov processed this record on July 24, 2014