Ischemic StrokePhase 4THERAPYNCT01429350
Assess the Penumbra System in the Treatment of Acute Stroke
A Phase 4 study testing intravenous (IV) recombinant human tissue plasminogen activator (rtPA) and Penumbra System in people with Ischemic Stroke, run by Penumbra Inc. at 4 sites in United States.
Trial summary
The purpose of this trial is to assess the safety and effectiveness of the Penumbra System as an adjunctive treatment to intravenous (IV) recombinant human tissue plasminogen activator (rtPA)in patients with acute ischemic stroke from large vessel occlusion in the brain. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Ischemic Stroke
- What is being tested?
- intravenous (IV) recombinant human tissue plasminogen activator (rtPA) and Penumbra System
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 108 participants
- Where
- 4 sitesUnited States
- Study dates
- May 2012to Oct 2016
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- From 18 to 85 years of age
- Present with symptoms consistent with an acute ischemic stroke and eligible for IV rtPA therapy (patients presenting 3-4.5 hrs from symptom onset are not eligible if they are >80 yrs of age, have a history of stroke and diabetes, anticoagulant use (even if INR is <1.7) and have a NIHSS score >25
- Evidence of a large vessel occlusion in the anterior circulation with a clot length of 8mm or longer
- NIH Stroke Scale (NIHSS) score 8 or greater or aphasic at presentation
- Signed informed consent
Who cannot join
- History of stroke in the past 3 months.
- Females who are pregnant
- Pre-existing neurological or psychiatric disease that could confound the study results such as a pre-stroke mRS score 1 or greater
- Known severe allergy to contrast media
- Uncontrolled hypertension (defined as systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg)
- CT evidence of the following conditions at randomization:
Show all 21Show fewer
- Significant mass effect with midline shift
- Any acute ischemic changes in >1/3 of the affected middle cerebral artery territory
- Evidence of intracranial hemorrhage
- Angiographic evidence of tantem extracranial occlusion or an arterial stenosis proximal to the occlusion that requires treatment prior to thrombus removal. Moderate stenosis not requiring treatment is not an exclusion
- Angiographic evidence of preexisting arterial injury
- Rapidly improving neurological status prior to randomization
- Bilateral stroke
- Intracranial tumors
- Known history of cerebral aneurysm or arteriovenous malfunction
- Known hemorrhagic diathesis, coagulation deficiency, or on anticoagulant therapy with an International Normalized Ratio (INR) of >1.7
- Baseline platelets <50,000
- Use of IV heparin in the past 48 hours with PPT >1.5 times the normalized ratio
- Pre-treatment glucose <50mg/dL or >300mg/dL
- Life expectancy less than 90 days prior to stroke onset
- Participation in another clinical investigation that could confound the evaluation of the study device
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Neurosurgery, Rush University Medical Center
Chicago, Illinois, 60612
Endovascular Surgical Neuroradiology, Swedish Medical Center
Denver, Colorado, 80112
Department of Neurological Surgery
Gainesville, Florida, 32610
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
About this study
Official title: The THERAPY Trial: The Randomized, Concurrent Controlled Trial to Assess the Penumbra System's Safety and Effectiveness in the Treatment of Acute Stroke
The purpose of this trial is to assess the safety and effectiveness of the Penumbra System as an adjunctive treatment to intravenous (IV) recombinant human tissue plasminogen activator (rtPA)in patients with acute ischemic stroke from large vessel occlusion in the brain. IV rtPA is the only drug approved for the treatment of acute ischemic stroke but it does not work very well in cases where the stroke is caused by a large vessel occlusion. The hypothesis being tested is to determine if the addition of a treatment by a mechanical thrombectomy device like the Penumbra System can improve the clinical outcome of the patient over just using IV rtPA alone.
Read the detailed description
Current therapies for acute stroke are limited to the intravenous administration of a intravenous (IV) recombinant human tissue plasminogen activator (rtPA) for thrombolysis of the affected cerebral arteries within 3-4.5 hours from symptom onset, and the use of intra-arterial (IA) endovascular mechanical clot retrieval devices within 8 hours from ictus, all of which have limitations as mono therapies. For example, IV rtPA may not be very efficacious in large vessel occlusion and the long term effects of mechanical thrombectomy devices on patient functional outcome is unknown. This is a randomized, concurrent controlled study to assess the safety and effectiveness of the Penumbra System as adjunctive therapy to IV rtPA in the acute intervention of acute ischemic stroke. Patients presenting with symptoms of acute ischemic stroke who have evidence of a large clot burden (clot length > 8mm) in the anterior circulation will be assigned to either IV rtPA therapy alone (0.9mg/kg to a maximum of 90mg) or a combined IV rtPA therapy (0.9mg/kg to a maximum of 90mg) and intra-arterial (IA) adjunctive treatment with the Penumbra System. Each treated patient will be followed and assessed for 3 months after enrollment.
- Conditions
- Ischemic Stroke
- Being tested
- intravenous (IV) recombinant human tissue plasminogen activator (rtPA), Penumbra System
- Keywords
- ischemic stroke, acute intervention, thrombolysis, rtPA, internal carotid artery, middle cerebral artery, mechanical thrombectomy, Penumbra System, clot length, mRS, NIHSS
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
intravenous (IV) recombinant human tissue plasminogen activator (rtPA)Drug
Also called recombinant tissue plasminogen activator, Alteplase
0.9mg/kg to a maximum of 90mg
Penumbra SystemDevice
The Penumbra System is an aspiration based mechanical thrombectomy device
| Study group | Role | What they receive |
|---|---|---|
| IV rtPA | Active comparator | IV infusion of rtPA at 0.9mg/kg to a maximum of 90mg Receives: Drug: intravenous (IV) recombinant human tissue plasminogen activator (rtPA) |
| IV rtPA and IA Penumbra System | Experimental | Dual IV rtPA therapy (0.9mg/kg to a maximum of 90mg) and IA adjunctive treatment with the Penumbra System Receives: Device: Penumbra System |
What is being measured
The primary outcome is the main question the study is designed to answer.
Good Functional Outcome as Defined by a Modified Rankin Score of 0-2
The assessor is blinded to patient treatment assignment.
Measured: 90 days
Incidence of All Serious Adverse Events
A Serious Adverse Event is defined as an event that:
- Led to death
- Led to a serious deterioration in the health of the patient that:
- Resulted in life-threatening illness or injury
- Resulted in permanent impairment of a body structure or a body function
- Required in-patient hospitalization or prolongation of existing hospitalization
- Resulted in medical or surgical intervention to arrest permanent impairment to body structure or a body function
- Led to fetal distress, fetal death or a congenital abnormality or birth defect
Measured: 90 days
Secondary outcomes (2)
Good Clinical Outcome
Good clinical outcome at 30 days post-procedure as defined by a 10 points or more improvement in the NIH stroke scale score at Discharge, a NIH stroke scale score of 0-1 at Discharge; or a 30-day modified Rankin scale score of 0-2
Measured: 30 days
Incidence of Symptomatic and Asymptomatic Intracranial Hemorrhage
A symptomatic intracranial hemorrhage is defined as 24 hour CT evidence of an ECASS defined ICH and a 4-point or more worsening of the NIH Stroke Scale score
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2011 (estimated)
- Study startMay 2012
- Primary completionOct 2016
- Study completionOct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 108 participants (actual)
Sponsor and investigators
- Lead sponsor
- Penumbra Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- J Mocco, MD, MS, Principal investigator, Vanderbilt University Medical CenterPooja Khatri, MD, Principal investigator, Department of Neurology, University of CincinnatiOsama Zaidat, MD, MSc, Principal investigator, Neurointerventional Program, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01429350
- Sponsor's protocol ID
- CLP 4338
- Acronym
- THERAPY
- Status last verified
- Sep 2020
- First submitted
- 2 Sep 2011
- Last updated
- 22 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Yoo AJ, Khatri P, Mocco J, Zaidat OO, Gupta R, Frei D, Lopes D, Shownkeen H, Berkhemer OA, Meyer D, Hak SS, Kuo SS, Buell H, Bose A, Sit SP, von Kummer R; THERAPY Trial Investigators. Impact of Thrombus Length on Outcomes After Intra-Arterial Aspiration Thrombectomy in the THERAPY Trial. Stroke. 2017 Jul;48(7):1895-1900. doi: 10.1161/STROKEAHA.116.016253. Epub 2017 Jun 8.
PubMed 28596447
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The THERAPY Trial: The Randomized, Concurrent Controlled Trial to Assess the Penumbra System's Safety and Effectiveness in the Treatment of Acute Stroke
- ClinicalTrials.gov ID
- NCT01429350
- Acronym / sponsor ID
- THERAPY / CLP 4338
- Conditions
- Ischemic Stroke
- Keywords
- ischemic stroke, acute intervention, thrombolysis, rtPA, internal carotid artery, middle cerebral artery, mechanical thrombectomy, Penumbra System
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 108 participants (actual)
- Lead sponsor
- Penumbra Inc.Industry (pharma, biotech, devices)
- Study start
- May 2012
- Primary completion
- Oct 2016 (actual)
- Study completion
- Oct 2016 (actual)
- First posted
- 7 Sep 2011 (estimated)
- Results
- Posted 22 Sep 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this trial is to assess the safety and effectiveness of the Penumbra System as an adjunctive treatment to intravenous (IV) recombinant human tissue plasminogen activator (rtPA)in patients with acute ischemic stroke from large vessel occlusion in the brain. IV rtPA is the only drug approved for the treatment of acute ischemic stroke but it does not work very well in cases where the stroke is caused by a large vessel occlusion. The hypothesis being tested is to determine if the addition of a treatment by a mechanical thrombectomy device like the Penumbra System can improve the clinical outcome of the patient over just using IV rtPA alone.
Detailed description
Current therapies for acute stroke are limited to the intravenous administration of a intravenous (IV) recombinant human tissue plasminogen activator (rtPA) for thrombolysis of the affected cerebral arteries within 3-4.5 hours from symptom onset, and the use of intra-arterial (IA) endovascular mechanical clot retrieval devices within 8 hours from ictus, all of which have limitations as mono therapies. For example, IV rtPA may not be very efficacious in large vessel occlusion and the long term effects of mechanical thrombectomy devices on patient functional outcome is unknown. This is a randomized, concurrent controlled study to assess the safety and effectiveness of the Penumbra System as adjunctive therapy to IV rtPA in the acute intervention of acute ischemic stroke. Patients presenting with symptoms of acute ischemic stroke who have evidence of a large clot burden (clot length > 8mm) in the anterior circulation will be assigned to either IV rtPA therapy alone (0.9mg/kg to a maximum of 90mg) or a combined IV rtPA therapy (0.9mg/kg to a maximum of 90mg) and intra-arterial (IA) adjunctive treatment with the Penumbra System. Each treated patient will be followed and assessed for 3 months after enrollment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IV rtPA | Active comparator | Drug: intravenous (IV) recombinant human tissue plasminogen activator (rtPA)IV infusion of rtPA at 0.9mg/kg to a maximum of 90mg |
| IV rtPA and IA Penumbra System | Experimental | Device: Penumbra SystemDual IV rtPA therapy (0.9mg/kg to a maximum of 90mg) and IA adjunctive treatment with the Penumbra System |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- From 18 to 85 years of age
- Present with symptoms consistent with an acute ischemic stroke and eligible for IV rtPA therapy (patients presenting 3-4.5 hrs from symptom onset are not eligible if they are >80 yrs of age, have a history of stroke and diabetes, anticoagulant use (even if INR is <1.7) and have a NIHSS score >25
- Evidence of a large vessel occlusion in the anterior circulation with a clot length of 8mm or longer
- NIH Stroke Scale (NIHSS) score 8 or greater or aphasic at presentation
- Signed informed consent
Key exclusion criteria (21 listed)
- History of stroke in the past 3 months.
- Females who are pregnant
- Pre-existing neurological or psychiatric disease that could confound the study results such as a pre-stroke mRS score 1 or greater
- Known severe allergy to contrast media
- Uncontrolled hypertension (defined as systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg)
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 |
|---|---|---|
| intravenous (IV) recombinant human tissue plasminogen activator (rtPA)Also: recombinant tissue plasminogen activator, Alteplase0.9mg/kg to a maximum of 90mg | Drug | IV rtPA |
| Penumbra SystemThe Penumbra System is an aspiration based mechanical thrombectomy device | Device | IV rtPA and IA Penumbra System |
Primary outcome
Good Functional Outcome as Defined by a Modified Rankin Score of 0-2
Time frame: 90 days
The assessor is blinded to patient treatment assignment.
Incidence of All Serious Adverse Events
Time frame: 90 days
A Serious Adverse Event is defined as an event that: 1. Led to death 2. Led to a serious deterioration in the health of the patient that: * Resulted in life-threatening illness or injury * Resulted in permanent impairment of a body structure or a body function * Required in-patient hospitalization or prolongation of existing hospitalization * Resulted in medical or surgical intervention to arrest permanent impairment to body structure or a body function * Led to fetal distress, fetal death or a congenital abnormality or birth defect
2 secondary outcomes
Good Clinical Outcome
Time frame: 30 days
Incidence of Symptomatic and Asymptomatic Intracranial Hemorrhage
Time frame: 90 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28596447Yoo AJ, Khatri P, Mocco J, Zaidat OO, Gupta R, Frei D, Lopes D, Shownkeen H, Berkhemer OA, Meyer D, Hak SS, Kuo SS, Buell H, Bose A, Sit SP, von Kummer R; THERAPY Trial Investigators. Impact of Thrombus Length on Outcomes After Intra-Arterial Aspiration Thrombectomy in the THERAPY Trial. Stroke. 2017 Jul;48(7):1895-1900. doi: 10.1161/STROKEAHA.116.016253. Epub 2017 Jun 8.
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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.
J Mocco, MD, MS principal investigator
Vanderbilt University Medical Center
Pooja Khatri, MD principal investigator
Department of Neurology, University of Cincinnati
Osama Zaidat, MD, MSc principal investigator
Neurointerventional Program, Medical College of Wisconsin
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing intravenous (IV) recombinant human tissue plasminogen activator (rtPA) and Penumbra System in people with Ischemic Stroke, run by Penumbra Inc. at 4 sites in United States.
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 21 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 22 Sep 2020. 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 United States. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Good Functional Outcome as Defined by a Modified Rankin Score of 0-2 (time frame: 90 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01429350, which also lists 1 linked publication.
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 22 Sep 2020.