A Trial Using Double-Bolus THR-100 Versus Streptokinase

NCT01305226 | Completed Phase 3 DMC

• 1 other identifier: BBIL/STA/05/2007
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Acute Myocardial Infarction

Keywords

THR 100

Outcome Measures

Primary Outcomes (1)

• 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)

  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.

  up to 4 weeks

Secondary Outcomes (1)

• To evaluate the safety profile of THR-100 in comparison with Streptokinase

  up to 4 weeks

Study Arms (2)

Test - THR-100

EXPERIMENTAL

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

Streptokinase

ACTIVE COMPARATOR

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

Interventions

THR-100 DRUG

THR-100: 15 mg double-bolus (15mg/15ml), separated by 30 minutes (total 30 mg)

Also known as: Staphylokinase

Test - THR-100

Streptokinase DRUG

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.

Also known as: Streptase

Streptokinase

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged 30 to \< 75 years inclusive.
• 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.
• Patients must be in the hospital or the emergency department and able to receive the study medication within 12 hours of onset of symptoms.
• Females of child-bearing age, not using a generally accepted method of contraception must have a negative urine pregnancy test.
• NB Verbal or written consent should be followed by written informed consent from the patient at the earliest subsequent opportunity.

You may not qualify if:

• Previous administration of staphylokinase.
• Active bleeding or known hemorrhagic diathesis.
• Any history of stroke, transient ischemic attack, dementia, or structural CNS damage e.g. neoplasm, aneurysm, AV malformation.
• Major surgery or trauma within the past 3 months.
• Significant hypertension i.e. SBP 180 mm Hg and/or DBP 110 mm Hg at any time from admission to randomization.
• Current treatment with vitamin K antagonists resulting with an INR \> 1.5.
• Anticipated difficulty with vascular access.
• Prolonged (\>10 min) cardiopulmonary resuscitation or cardiogenic shock.
• Patients who have participated in an investigational drug study within the past 30 days.
• Pregnancy or lactation, parturition within the previous 30 days.
• Any serious concomitant systemic or life limiting disorder that would be incompatible with the trial
• Patients known to have a history of or life limiting malignant disease or HIV.
• Significant hepatic or renal dysfunction or any other condition which, in the opinion of the Investigator, makes the patient unsuitable for study entry.
• Previous participation in this trial

Sponsors & Collaborators

• Bharat Biotech International Limited: lead

Study Sites (4)

Sri Jayadeva Institute of Cardiology.

Bangalore, Karnataka, 560 069, India

Location

Narayana Hrudayalaya

Bangalore, Karnataka, 560 099, India

Location

Lotus Super speciality Hospita

Agra, Uttar Pradesh, 282 002, India

Location

Institute of Post Graduate Medical Education and Research (IPGMER)

Kolkata, West Bengal, 700 020, India

Location

MeSH Terms

Interventions

auR protein, Staphylococcus aureus; Streptokinase

Intervention Hierarchy (Ancestors)

Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Dr.A Singh, MBBS, MD

  Bharat Biotech Int. Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 28, 2010
• First Posted: February 28, 2011
• Study Start: October 1, 2010
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2011
• Last Updated: February 23, 2021

Record last verified: 2021-02

Locations

IN (4)