Acute Ischemic StrokePhase 1/2NCT01253512
Study to Assess the Safety and Efficacy of THR-18 When Administered to Patients Suffering Acute Ischemic Stroke and Treated With Tissue Plasminogen Activator (tPA)
A Phase 1/2 study testing THR-18 in people with Acute Ischemic Stroke, run by Thrombotech Ltd. at 1 site in Israel.
Trial summary
This will be a randomized, double-blind, placebo-controlled, multi-center, multi-national, escalating dose, pilot study comparing two doses of THR-18 to placebo when administered to patients suffering acute ischemic stroke and treated with Tissue Plasminogen Activator (tPA). Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Acute Ischemic Stroke
- What is being tested?
- THR-18
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 1 siteIsrael
- Study dates
- Mar 2011to Dec 2011
- Phase
- Phase 1/2
- 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 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female.
- Diagnosis of acute ischemic stroke onset less than 3 hours prior to the planned start of intravenous Tissue Plasminogen Activator (tPA).
- Have suffered an acute hemispheric ischemic stroke, defined as acute, focal, neurological deficit(s) and secondary to a presumed vascular event.
- Age 18-85 years both inclusive.
- Able to sign informed consent.
Who cannot join
- Participation in another study with an investigational drug or device within 30 days of study entry, prior participation in the present study, or planned participation in another therapeutic trial, prior to the final (day 30) assessment in this trial.
- Time interval since stroke onset of less than 3 hours is impossible to determine with high degree of confidence.
- Symptoms suggestive of subarachnoid hemorrhage, even if computed tomography perfusion scan(CT)or magnetic resonance imaging (MRI) scan is negative for hemorrhage.
- Evidence of acute myocardial infarction.
- Acute Pericarditis
- Patients who would refuse blood transfusions if medically indicated.
Show all 42Show fewer
- Neurological deficit that has led to stupor or coma (National Institutes of Health Stroke Scale (NIHSS) level of consciousness score greater than or equal to 2).
- High clinical suspicion of septic embolus.
- Minor stroke with non-disabling deficit or rapidly improving neurological symptoms.
- Baseline NIHSS greater than 18 for left hemisphere stroke or greater than 15 for others.
- Evidence of acute or chronic Intra cranial Hemorrhage (ICH) by head CT or MRI.
- CT or MRI evidence of non-vascular cause for the neurological symptoms.
- Signs of mass effect causing shift of midline structures on CT or MRI.
- Persistent hypertension with systolic BP greater than 185 mmHg or diastolic BP greater than 110 mmHg not controlled by antihypertensive therapy or requiring nitroprusside for control.
- Blood glucose greater than 200 mg/dl.
- Anticipated need for major surgery within 72 hours after start of study drugs, e.g., carotid endarterectomy, hip fracture repair.
- Any intracranial surgery, intraspinal surgery, or serious head trauma (any head injury that required hospitalization) within the past 3 months.
- Have suffered a stroke within 90 days of the screening/baseline assessments that is either diagnostically confirmed or assumed to be in the same cerebral territory as is the current acute stroke.
- History of ICH at any time in the past.
- Major trauma at the time of stroke, e.g., hip fracture.
- Presence or history of intracranial neoplasm (except small meninigiomas) or arteriovenous malformation.
- Intracranial aneurysm, unless surgically or endovascularly treated more than 3 months before the current acute stroke.
- Seizure at the onset of stroke.
- Active internal bleeding.
- Major hemorrhage (requiring transfusion, surgery or hospitalization) in the past 21 days.
- Major surgery, serious trauma, lumbar puncture, arterial puncture at a non-compressible site, or biopsy of a parenchymal organ in last 14 days. Major surgical procedures include but are not limited to the following: major thoracic or abdominopelvic surgery, neurosurgery, major limb surgery, carotid endarterectomy or other vascular surgery, and organ transplantation. For non-listed procedures, the operating surgeon should be consulted to assess the risk.
- Presumed or documented history of vasculitis.
- Known systemic bleeding or platelet disorder, e.g., von Willebrand's disease, hemophilia, ITP, TTP, others.
- Platelet counts less than 100,000 cells/micro L.
- Congenital or acquired coagulopathy (e.g., secondary to anticoagulants).
- Life expectancy less than 3 months.
- Severe renal failure.
- AST or ALT greater than 3 times the upper limit of normal for the local laboratory.
- Any administration of a thrombolytic drug in the prior 7 days.
- Treatment of the qualifying stroke with intravenous heparin unless aPTT prolongation is no greater than 2 seconds above the upper limit of normal for local laboratory prior to study drug initiation.
- Treatment of the qualifying stroke with a low molecular weight heparin or heparinoid.
- Known hypersensitivity to tPA.
- Anticoagulation (evidenced by abnormal INR, aPTT, or platelet count) caused by herbal therapy.
- Ischemic changes on screening CT of greater than approximately one third of the territory of the middle cerebral artery territory by qualitative assessment.
- Female of childbearing potential (less than 2 years' postmenopausal or not surgically sterilized) who is not willing to use adequate and effective birth control measures for the duration of the trial. Effective birth control measures include hormonal contraception, a barrier method such as a diaphragm, intrauterine device (IUD) and/or condom with spermicide (IUD, diaphragm, condoms alone or the rhythm method are not considered reliable methods).
- Have a positive urine pregnancy test at screening/baseline or be a lactating female.
- Any condition that in the investigator's judgement precludes participation in the study.
Trial locations and contacts
1 site in 1 country.
Israel1 site
Hadassah Medical Center,
Jerusalem, 91120
Ronen R. Leker, MD, FAHA, 972-2-6776192, leker@hadassah.org.il
Ronen R Leker, MD, FAHA
About this study
Official title: Double Blind, Placebo Controlled, Escalating Single-dose, Pilot Study to Assess the Safety of THR-18 When Administered to Patients Suffering Acute Ischemic Stroke and Treated With Tissue Plasminogen Activator (tPA)
This will be a randomized, double-blind, placebo-controlled, multi-center, multi-national, escalating dose, pilot study comparing two doses of THR-18 to placebo when administered to patients suffering acute ischemic stroke and treated with Tissue Plasminogen Activator (tPA).
The study hypothesis is that THR-18 will be safe and well tolerated in subjects suffering acute ischemic stroke and treated with Thrombolysis.
Read the detailed description
This will be a randomized, double-blind, placebo-controlled, multi-center, multi-national, escalating dose, pilot study comparing two doses of THR-18 (0.25 and 0.5 mg/kg) to placebo when administered to patients suffering acute ischemic stroke and treated with Tissue Plasminogen Activator (tPA).
A total of 22 subjects suffering from acute ischemic stroke that are eligible for tPA treatment will be recruited into the study. Eligible for recruitment are patients with an entry National Institutes of Health Stroke Scale (NIHSS) score of 5-18 and a clinical syndrome that includes at least 1 of the following: language dysfunction, visual field defect or neglect (specifically, at least 1 point on NIHSS items 3 or 9 or 11). Alternatively, patients without at least 1 point on NIHSS items 3, 9 or 11 may be enrolled if routine diffusion-weighted magnetic resonance imaging (MRI) or computed tomography perfusion scan (CT) indicates that the acute stroke involves the cerebral cortex, and as long as the overall acute neurological deficit is within the range of 5-18 NIHSS points.
Stroke onset will be defined as the time the patient was last known to be without a new clinical deficit. Patients whose symptoms started more than 3 hours before presentation are not eligible for the study. If the stroke started during sleep, stroke onset will be recorded as the time the patient was last known to be normal.
Patients will be recruited after obtaining informed consent. Female subjects of childbearing potential (less than 2 years' postmenopausal or not surgically sterilized) will have a urine pregnancy test at baseline and will be required to use adequate and effective birth control measures for the duration of the trial. Effective birth control measures include hormonal contraception, a barrier method such as a diaphragm, intrauterine device (IUD) and/or condom with spermicide (IUD, diaphragm, condoms alone or the rhythm method are not considered reliable methods).
Patients will be randomized to receive either 0.25 or 0.5 mg/kg of THR-18 or placebo in an escalating manner. tPA should be administered as 0.9 mg/kg (10% of the total dose as an Intra Venous(IV) bolus and the reminder infused IV over 60 minutes). THR-18 bolus should be given immediately prior to the tPA bolus, and the 60 min infusion of both THR-18 and tPA will be done in parallel.
- Conditions
- Acute Ischemic Stroke
- Being tested
- THR-18, Placebo
- Keywords
- Ischemic Stroke, Thrombolysis
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
THR-18Drug
A single 0.25 or 0.5 mg/kg of THR-18 in combination with tPA treatment.
PlaceboDrug
Intravenous
| Study group | Role | What they receive |
|---|---|---|
| THR-18 0.25mg/kg | Experimental | Treatment with combination with Tissue Plasminogen Activator (tPA) treatment Receives: Drug: THR-18 |
| Placebo treatment | Placebo comparator | Treatment in combination with Tissue Plasminogen Activator (tPA) treatment Receives: Drug: Placebo |
| THR-18 0.5mg/kg | Experimental | Treatment in combination with Tissue Plasminogen Activator (tPA) treatment Receives: Drug: THR-18 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability
Safety and tolerability parameters include evaluation of:
- No of subjects experiencing adverse events throughout the study
- Changes for start of study in clinical safety laboratory blood tests
- Changes in hemodynamic parameters throughout the study
- Number of subjects experiencing intra-cranial hemorrhage throughout the study
Measured: 3 months
Secondary outcomes (1)
Number of subjects achieving favourable neurological outcome as assessed by National Institutes of Health Stroke Scale (NIHSS) NIHSS and Modified Rankin Scale (mRS) categorical analysis at 1 and 3 months post drug administration.
Excellent neurological outcome defined as:
NIHSS ≤ 1 or mRS at ≤ 1
Good neurological outcome defined as:
NIHSS = drop of at least 8 points from the initial stroke mRS ≤ 2
Measured: 30 and 90 days from stroke onset
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2010 (estimated)
- Study startMar 2011
- Primary completionDec 2011 (estimated)
- Study completionDec 2011 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Ischemic StrokeStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 22 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Thrombotech Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Ronen R. Leker, MD, FAHA, Principal investigator, Hadassah Medical Organization
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01253512
- Sponsor's protocol ID
- THR-2010-01
- Other IDs
- THR-18 pilot stroke study
- Status last verified
- Dec 2010
- First submitted
- 30 Nov 2010
- Last updated
- 3 Dec 2010
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double Blind, Placebo Controlled, Escalating Single-dose, Pilot Study to Assess the Safety of THR-18 When Administered to Patients Suffering Acute Ischemic Stroke and Treated With Tissue Plasminogen Activator (tPA)
- ClinicalTrials.gov ID
- NCT01253512
- Acronym / sponsor ID
- THR-2010-01
- Conditions
- Acute Ischemic Stroke
- Keywords
- Ischemic Stroke, Thrombolysis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 22 participants (estimated)
- Lead sponsor
- Thrombotech Ltd.Industry (pharma, biotech, devices)
- Study start
- Mar 2011
- Primary completion
- Dec 2011 (estimated)
- Study completion
- Dec 2011 (estimated)
- First posted
- 3 Dec 2010 (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 will be a randomized, double-blind, placebo-controlled, multi-center, multi-national, escalating dose, pilot study comparing two doses of THR-18 to placebo when administered to patients suffering acute ischemic stroke and treated with Tissue Plasminogen Activator (tPA).
The study hypothesis is that THR-18 will be safe and well tolerated in subjects suffering acute ischemic stroke and treated with Thrombolysis.
Detailed description
This will be a randomized, double-blind, placebo-controlled, multi-center, multi-national, escalating dose, pilot study comparing two doses of THR-18 (0.25 and 0.5 mg/kg) to placebo when administered to patients suffering acute ischemic stroke and treated with Tissue Plasminogen Activator (tPA).
A total of 22 subjects suffering from acute ischemic stroke that are eligible for tPA treatment will be recruited into the study. Eligible for recruitment are patients with an entry National Institutes of Health Stroke Scale (NIHSS) score of 5-18 and a clinical syndrome that includes at least 1 of the following: language dysfunction, visual field defect or neglect (specifically, at least 1 point on NIHSS items 3 or 9 or 11). Alternatively, patients without at least 1 point on NIHSS items 3, 9 or 11 may be enrolled if routine diffusion-weighted magnetic resonance imaging (MRI) or computed tomography perfusion scan (CT) indicates that the acute stroke involves the cerebral cortex, and as long as the overall acute neurological deficit is within the range of 5-18 NIHSS points.
Stroke onset will be defined as the time the patient was last known to be without a new clinical deficit. Patients whose symptoms started more than 3 hours before presentation are not eligible for the study. If the stroke started during sleep, stroke onset will be recorded as the time the patient was last known to be normal.
Patients will be recruited after obtaining informed consent. Female subjects of childbearing potential (less than 2 years' postmenopausal or not surgically sterilized) will have a urine pregnancy test at baseline and will be required to use adequate and effective birth control measures for the duration of the trial. Effective birth control measures include hormonal contraception, a barrier method such as a diaphragm, intrauterine device (IUD) and/or condom with spermicide (IUD, diaphragm, condoms alone or the rhythm method are not considered reliable methods).
Patients will be randomized to receive either 0.25 or 0.5 mg/kg of THR-18 or placebo in an escalating manner. tPA should be administered as 0.9 mg/kg (10% of the total dose as an Intra Venous(IV) bolus and the reminder infused IV over 60 minutes). THR-18 bolus should be given immediately prior to the tPA bolus, and the 60 min infusion of both THR-18 and tPA will be done in parallel.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| THR-18 0.25mg/kg | Experimental | Drug: THR-18Treatment with combination with Tissue Plasminogen Activator (tPA) treatment |
| Placebo treatment | Placebo comparator | Drug: PlaceboTreatment in combination with Tissue Plasminogen Activator (tPA) treatment |
| THR-18 0.5mg/kg | Experimental | Drug: THR-18Treatment in combination with Tissue Plasminogen Activator (tPA) treatment |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female.
- Diagnosis of acute ischemic stroke onset less than 3 hours prior to the planned start of intravenous Tissue Plasminogen Activator (tPA).
- Have suffered an acute hemispheric ischemic stroke, defined as acute, focal, neurological deficit(s) and secondary to a presumed vascular event.
- Age 18-85 years both inclusive.
- Able to sign informed consent.
Key exclusion criteria (42 listed)
- Participation in another study with an investigational drug or device within 30 days of study entry, prior participation in the present study, or planned participation in another therapeutic trial, prior to the final (day 30) assessment in this trial.
- Time interval since stroke onset of less than 3 hours is impossible to determine with high degree of confidence.
- Symptoms suggestive of subarachnoid hemorrhage, even if computed tomography perfusion scan(CT)or magnetic resonance imaging (MRI) scan is negative for hemorrhage.
- Evidence of acute myocardial infarction.
- Acute Pericarditis
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-18A single 0.25 or 0.5 mg/kg of THR-18 in combination with tPA treatment. | Drug | THR-18 0.25mg/kg, THR-18 0.5mg/kg |
| PlaceboIntravenous | Drug | Placebo treatment |
Primary outcome
Safety and tolerability
Time frame: 3 months
Safety and tolerability parameters include evaluation of: 1. No of subjects experiencing adverse events throughout the study 2. Changes for start of study in clinical safety laboratory blood tests 3. Changes in hemodynamic parameters throughout the study 4. Number of subjects experiencing intra-cranial hemorrhage throughout the study
1 secondary outcome
Number of subjects achieving favourable neurological outcome as assessed by National Institutes of Health Stroke Scale (NIHSS) NIHSS and Modified Rankin Scale (mRS) categorical analysis at 1 and 3 months post drug administration.
Time frame: 30 and 90 days from stroke onset
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2010.
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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.
Ronen R. Leker, MD, FAHA principal investigator
Hadassah Medical Organization
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing THR-18 in people with Acute Ischemic Stroke, run by Thrombotech Ltd. at 1 site in Israel.
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 5 inclusion and 42 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: status not confirmed, as of the sponsor's last update on 3 Dec 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Arnon Aharon (972545500702, arnon@rnd-is.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability (time frame: 3 months). 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 3 Dec 2010.