Acute Myocardial InfarctionPhase 3THR-100NCT01305226
A Trial Using Double-Bolus THR-100 Versus Streptokinase
A Phase 3 study testing THR-100 and Streptokinase in people with Acute Myocardial Infarction, run by Bharat Biotech International Limited at 4 sites in India.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 to 75 years
- Conditions the study is for
- Acute Myocardial Infarction
- What is being tested?
- THR-100 and Streptokinase
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 4 sitesIndia
- Study dates
- Oct 2010to Aug 2011
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 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.
- NB Verbal or written consent should be followed by written informed consent from the patient at the earliest subsequent opportunity.
Who cannot join
- 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.
Show all 14Show fewer
- 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
Trial locations and contacts
4 sites in 1 country.
India4 sites
Lotus Super speciality Hospita
Agra, Uttar Pradesh, 282 002
Sri Jayadeva Institute of Cardiology.
Bangalore, Karnataka, 560 069
Narayana Hrudayalaya
Bangalore, Karnataka, 560 099
Institute of Post Graduate Medical Education and Research (IPGMER)
Kolkata, West Bengal, 700 020
About this study
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
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.
Read the detailed description
STUDY SUMMARY/PROTOCOL OUTLINE
Protocol Number: BBIL/STA/O5/2007 Protocol Name: A PROSPECTIVE PHASE III PARALLEL, RANDOMISED CONTROLLED TRIAL USING DOUBLE-BOLUS THR-100 (RECOMBINANT STAPHYLOKINASE) Vs STREPTOKINASE IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION
Drug under Study: THR-100 (Recombinant Staphylokinase)
Intended Indication: Acute Myocardial Infarction
Study Design: Randomized, Parallel Group, Multicenter and Active-Comparator Trial.
Patient Population: Patients aged 30 to ≤ 75 years presenting with acute myocardial infarction within 12 hours of onset of symptoms presumed secondary to an acute myocardial infarction.
Number of Patients: 120 subjects are to be recruited into the trial, with patients randomized in a 1:1 allocation ratio to THR-100 and Streptokinase over three centers. This sample size of 120 subjects provides power of 0.90 with a significance level of 0.05 to yield a statistically significant early patency difference.
Primary Objectives: 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) Secondary Objectives: To evaluate the safety profile of recombinant SAK in comparison with Streptokinase.
Dose Levels: Dose levels (all administered intravenously). THR-100: 15 mg double-bolus (15mg/15ml), separated by 30 minutes (total 30 mg) 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.
Study Parameters: Primary endpoint:
- 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.
- Changes in cardiac Enzyme levels of CK-MB and Cardiac Troponin I or T at 6 hrs, 8 hrs, 12-16 hrs and 24 hours after start of thrombolytic therapy.
- Significant Relief of pain (a 3 point reduction on a 0-5 subjective scale) at end of 2 and 12 hrs after start of thrombolytic therapy. (0-No pain, 1-Slight pain, 2-Mild pain, 3-Moderate pain, 4- Severe pain, 5-Very severe pain).
- Assessment of culprit coronary vessel patency (TIMI- grade 3) at 90 minutes. (TIMI- Thrombolysis in myocardial infarction). Angiography shall be performed only in patients who fulfil the following guidelines
- No WPW or LBBB or IV-conduction block or Pacemaker rhythm. 2. ≥0.2 mV ST elevation in ≥2 leads V1-V6 and ≥0.3 mV ST elevation in ≥1 lead V1-V6 3. Sum of ST elevation in V1-V6 plus Sum of ST depression in II, III, aVF ≥0.8 mV (OR)
- No WPW or LBBB or IV-conduction block or Pacemaker rhythm.
- ≥0.1 mV ST elevation in ≥2 leads II, III,aVF and ≥0.2 mV ST elevation in ≥1 lead II, III, aVF 5). Sum of ST elevation in I-III, aVF plus Sum of ST depression in V1-V4 ≥0.6 mV.
Secondary endpoints:
Assessment of net clinical benefit, defined as reduced mortality, non-fatal stroke, clinically-evident intracranial hemorrhage, or recurrent myocardial infarction at thirty (30) days.
Assessment of the rates of the following in-hospital events as defined in Appendix 1:
- Heart failure,
- In-hospital death,
- Recurrent myocardial infarction,
- Refractory ischemia,
- need for urgent revascularization,
- Major complications (such as cardiogenic shock, major arrhythmias, pericarditis, tamponade, acute hemodynamically severe mitral regurgitation, acute ventricular septal defect),
Safety considerations:
- Stroke,
- Intracranial hemorrhage (see stroke),
- Major bleeding (other than intracranial hemorrhage),
- Bleeding other than major,
- Serious and non-serious adverse events (see Section 14),
- Allergic reactions,
- Laboratory data. Other angiographic end point CTFC (Corrected TIMI Frame Count), if Angiography performed.
- Conditions
- Acute Myocardial Infarction
- Being tested
- THR-100, Streptokinase
- Keywords
- THR 100
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
THR-100Drug
Also called Staphylokinase
THR-100: 15 mg double-bolus (15mg/15ml), separated by 30 minutes (total 30 mg)
StreptokinaseDrug
Also called Streptase
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.
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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. Receives: Drug: Streptokinase |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: up to 4 weeks
Secondary outcomes (1)
To evaluate the safety profile of THR-100 in comparison with Streptokinase
Assessment of net clinical benefit, defined as reduced mortality, non-fatal stroke, clinically-evident intracranial hemorrhage, or recurrent myocardial infarction at thirty (30) days.
Measured: up to 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2011 (estimated)
- Study startOct 2010
- Primary completionAug 2011
- Study completionAug 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myocardial InfarctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bharat Biotech International Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Dr.A Singh, MBBS, MD, Study director, Bharat Biotech Int. Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01305226
- Sponsor's protocol ID
- BBIL/STA/05/2007
- Acronym
- THR-100
- Status last verified
- Feb 2021
- First submitted
- 28 Dec 2010
- Last updated
- 23 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01305226
- Acronym / sponsor ID
- THR-100 / BBIL/STA/05/2007
- Conditions
- Acute Myocardial Infarction
- Keywords
- THR 100
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Bharat Biotech International LimitedIndustry (pharma, biotech, devices)
- Study start
- Oct 2010
- Primary completion
- Aug 2011 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 28 Feb 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
STUDY SUMMARY/PROTOCOL OUTLINE
Protocol Number: BBIL/STA/O5/2007 Protocol Name: A PROSPECTIVE PHASE III PARALLEL, RANDOMISED CONTROLLED TRIAL USING DOUBLE-BOLUS THR-100 (RECOMBINANT STAPHYLOKINASE) Vs STREPTOKINASE IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION
Drug under Study: THR-100 (Recombinant Staphylokinase)
Intended Indication: Acute Myocardial Infarction
Study Design: Randomized, Parallel Group, Multicenter and Active-Comparator Trial.
Patient Population: Patients aged 30 to ≤ 75 years presenting with acute myocardial infarction within 12 hours of onset of symptoms presumed secondary to an acute myocardial infarction.
Number of Patients: 120 subjects are to be recruited into the trial, with patients randomized in a 1:1 allocation ratio to THR-100 and Streptokinase over three centers. This sample size of 120 subjects provides power of 0.90 with a significance level of 0.05 to yield a statistically significant early patency difference.
Primary Objectives: 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) Secondary Objectives: To evaluate the safety profile of recombinant SAK in comparison with Streptokinase.
Dose Levels: Dose levels (all administered intravenously). THR-100: 15 mg double-bolus (15mg/15ml), separated by 30 minutes (total 30 mg) 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.
Study Parameters: Primary endpoint:
- 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.
- Changes in cardiac Enzyme levels of CK-MB and Cardiac Troponin I or T at 6 hrs, 8 hrs, 12-16 hrs and 24 hours after start of thrombolytic therapy.
- Significant Relief of pain (a 3 point reduction on a 0-5 subjective scale) at end of 2 and 12 hrs after start of thrombolytic therapy. (0-No pain, 1-Slight pain, 2-Mild pain, 3-Moderate pain, 4- Severe pain, 5-Very severe pain).
- Assessment of culprit coronary vessel patency (TIMI- grade 3) at 90 minutes. (TIMI- Thrombolysis in myocardial infarction). Angiography shall be performed only in patients who fulfil the following guidelines
- No WPW or LBBB or IV-conduction block or Pacemaker rhythm. 2. ≥0.2 mV ST elevation in ≥2 leads V1-V6 and ≥0.3 mV ST elevation in ≥1 lead V1-V6 3. Sum of ST elevation in V1-V6 plus Sum of ST depression in II, III, aVF ≥0.8 mV (OR)
- No WPW or LBBB or IV-conduction block or Pacemaker rhythm.
- ≥0.1 mV ST elevation in ≥2 leads II, III,aVF and ≥0.2 mV ST elevation in ≥1 lead II, III, aVF 5). Sum of ST elevation in I-III, aVF plus Sum of ST depression in V1-V4 ≥0.6 mV.
Secondary endpoints:
Assessment of net clinical benefit, defined as reduced mortality, non-fatal stroke, clinically-evident intracranial hemorrhage, or recurrent myocardial infarction at thirty (30) days.
Assessment of the rates of the following in-hospital events as defined in Appendix 1:
- Heart failure,
- In-hospital death,
- Recurrent myocardial infarction,
- Refractory ischemia,
- need for urgent revascularization,
- Major complications (such as cardiogenic shock, major arrhythmias, pericarditis, tamponade, acute hemodynamically severe mitral regurgitation, acute ventricular septal defect),
Safety considerations:
- Stroke,
- Intracranial hemorrhage (see stroke),
- Major bleeding (other than intracranial hemorrhage),
- Bleeding other than major,
- Serious and non-serious adverse events (see Section 14),
- Allergic reactions,
- Laboratory data. Other angiographic end point CTFC (Corrected TIMI Frame Count), if Angiography performed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Test - THR-100 | Experimental | Drug: THR-100120 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) |
| Streptokinase | Active comparator | Drug: Streptokinase120 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. |
Who may qualify
- Ages
- 30 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| THR-100Also: StaphylokinaseTHR-100: 15 mg double-bolus (15mg/15ml), separated by 30 minutes (total 30 mg) | Drug | Test - THR-100 |
| StreptokinaseAlso: StreptaseStreptokinase: 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 |
Primary outcome
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
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.
1 secondary outcome
To evaluate the safety profile of THR-100 in comparison with Streptokinase
Time frame: up to 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2021.
Related trials for Acute Myocardial Infarction
Enrolling by invitationPhase 3
Selatogrel Outcome Study in Suspected Acute Myocardial Infarction
Acute Myocardial Infarction
RecruitingObservational study
Assessment of Support With Impella® Best Practices in Acute Myocardial Infarction Complicated by Cardiogenic Shock
AMI Cardiogenic Shock
RecruitingObservational study
Cardiogenic Shock Working Group Registry
Cardiogenic Shock
Recruiting
CRP Apheresis in Infarct-Related Cardiogenic Shock
Cardiogenic Shock, Acute Myocardial Infarction (AMI)
RecruitingObservational study
Changes in Skeletal Muscle Thickness in Patients With Acute Heart Failure
Heart Failure, Muscle Atrophy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dr.A Singh, MBBS, MD study director
Bharat Biotech Int. Ltd.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing THR-100 and Streptokinase in people with Acute Myocardial Infarction, run by Bharat Biotech International Limited at 4 sites in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2021.