Acute Ischemic StrokePhase 3CLOTBUST-ERNCT01098981
Phase 3, Randomized, Placebo-Controlled, Double-Blinded Trial of the Combined Lysis of Thrombus With Ultrasound and Systemic Tissue Plasminogen Activator (tPA) for Emergent Revascularization in Acute Ischemic Stroke
A Phase 3 study testing Transcranial ultrasound as an adjunctive therapy to tPA in people with Acute Ischemic Stroke, run by Cerevast Therapeutics, Inc. at 1 site in United States.
Trial summary
This is a randomized, placebo-controlled, phase 3 clinical trial to evaluate the efficacy and safety of transcranial ultrasound (US) as an adjunctive therapy to tissue plasminogen activator (tPA) treatment in subjects with acute ischemic stroke. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Acute Ischemic Stroke
- What is being tested?
- Transcranial ultrasound as an adjunctive therapy to tPA
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 675 participants
- Where
- 1 siteUnited States
- Study dates
- May 2013to Apr 2015
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or females 18 - 80 years of age
- Subjects presenting within timeframe for intravenous tPA treatment approved by local regulatory authorities but no more than 4.5 hours from onset of symptoms
- No signs of intracranial bleeding on assessment by non-contrast CT
- Subjects with neurological deficits of a total NIHSS score ≥ 10 points
- Subjects that in the opinion of the treating physician require treatment with full dose IV tPA as standard of care per institutional standards
- SBP < 185 mmHg and DBP < 105 mmHg at baseline or after treatment of hypertension with medications prior to tPA bolus
Show all 12Show fewer
- Pre-morbid modified Rankin score of 0-1
- Provision of informed consent as demonstrated by the subject's signature or by the signature of the subject's authorized legal representative on the Informed Consent Form in accordance with all local and national regulations
- Co-signature on the Informed Consent Form by a qualified member of the study staff signifying that, in his/her professional opinion, informed consent has been obtained in accordance with all local and national regulations
- For subjects in the optional arterial recanalization substudy:
- Occlusion located in the intracranial carotid tee through mid M2 or proximal A2, or intracranial vertebrobasilar or P1/proximal P2 segments or tandem lesions
- Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min for patients undergoing CTA or MRA
Who cannot join
- Subjects with primary intra-arterial thrombolysis
- Females who are pregnant or breast feeding
- Subjects receiving other investigational drugs, procedures, or therapies within 30 days prior to study treatment
- Subjects with any standard contraindication for intravenous tPA therapy
- Significant concurrent medical/neurological conditions or test values that, in the opinion of the investigator, pose significant risk to the subject and warrant exclusion from the study
Trial locations and contacts
1 site in 1 country.
United States1 site
Cerevast Therapeutics, Inc.
Redmond, Washington, 98052-2431
About this study
Official title: A Phase 3, Randomized, Placebo-Controlled, Double-Blind Study of the Combined Lysis of Thrombus With Ultrasound and Systemic Tissue Plasminogen Activator (tPA) for Emergent Revascularization (CLOTBUST-ER) in Acute Ischemic Stroke
This is a randomized, placebo-controlled, phase 3 clinical trial to evaluate the efficacy and safety of transcranial ultrasound (US) as an adjunctive therapy to tissue plasminogen activator (tPA) treatment in subjects with acute ischemic stroke.
Read the detailed description
The primary objective of this trial is to provide information regarding the efficacy of a combined treatment with transcranial US and systemic tPA (Target group) compared to systemic tPA alone (Control group) in subjects with acute ischemic stroke. The primary efficacy endpoint is functional outcome at 3 months from stroke onset (modified Rankin Score ordinal shift analysis). The primary safety endpoint is the proportion of subjects in the Target vs Control group experiencing symptomatic intracranial hemorrhage (sICH) within 24 hours of treatment.
- Conditions
- Acute Ischemic Stroke
- Being tested
- Transcranial ultrasound as an adjunctive therapy to tPA, Standard of care tPA therapy for acute ischemic stroke
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial ultrasound as an adjunctive therapy to tPADevice
- tPA per approved labeling administered over 60 minutes
- Ultrasonic headframe with active insonation for 120 minutes
Standard of care tPA therapy for acute ischemic strokeDrug
- tPA per approved labeling administered over 60 minutes
- Ultrasonic headframe with sham (inactive) insonation for 120 minutes
| Study group | Role | What they receive |
|---|---|---|
| Target group | Experimental | A combined treatment with transcranial US and systemic tPA Receives: Device: Transcranial ultrasound as an adjunctive therapy to tPA |
| Control group | Active comparator | Systemic tPA alone Receives: Drug: Standard of care tPA therapy for acute ischemic stroke |
What is being measured
The primary outcome is the main question the study is designed to answer.
Modified Rankin score ordinal shift analysis
The primary objective of this study is to compare clinical recovery rates (modified Rankin score ordinal shift analysis) at 3 months after stroke onset.
Measured: 3 months
Secondary outcomes (1)
Symptomatic intracerebral hemorrhage
The secondary outcome is a comparison of the rates of symptomatic intracerebral hemorrhage within 0-24 hours from initiation of treatment.
Measured: 0-24 hours from treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2010 (estimated)
- Study startMay 2013
- Primary completionApr 2015
- Study completionApr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 675 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cerevast Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01098981
- Sponsor's protocol ID
- CEREVAST THERAPEUTICS CP-01
- Acronym
- CLOTBUST-ER
- Status last verified
- Apr 2015
- First submitted
- 2 Apr 2010
- Last updated
- 7 Apr 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Alexandrov AV, Kohrmann M, Soinne L, Tsivgoulis G, Barreto AD, Demchuk AM, Sharma VK, Mikulik R, Muir KW, Brandt G, Alleman J, Grotta JC, Levi CR, Molina CA, Saqqur M, Mavridis D, Psaltopoulou T, Vosko M, Fiebach JB, Mandava P, Kent TA, Alexandrov AW, Schellinger PD; CLOTBUST-ER Trial Investigators. Safety and efficacy of sonothrombolysis for acute ischaemic stroke: a multicentre, double-blind, phase 3, randomised controlled trial. Lancet Neurol. 2019 Apr;18(4):338-347. doi: 10.1016/S1474-4422(19)30026-2.
PubMed 30878103Schellinger PD, Alexandrov AV, Barreto AD, Demchuk AM, Tsivgoulis G, Kohrmann M, Alleman J, Howard V, Howard G, Alexandrov AW, Brandt G, Molina CA; CLOTBUSTER Investigators. Combined lysis of thrombus with ultrasound and systemic tissue plasminogen activator for emergent revascularization in acute ischemic stroke (CLOTBUST-ER): design and methodology of a multinational phase 3 trial. Int J Stroke. 2015 Oct;10(7):1141-8. doi: 10.1111/ijs.12536. Epub 2015 Jun 29.
PubMed 26120902
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Placebo-Controlled, Double-Blind Study of the Combined Lysis of Thrombus With Ultrasound and Systemic Tissue Plasminogen Activator (tPA) for Emergent Revascularization (CLOTBUST-ER) in Acute Ischemic Stroke
- ClinicalTrials.gov ID
- NCT01098981
- Acronym / sponsor ID
- CLOTBUST-ER / CEREVAST THERAPEUTICS CP-01
- Conditions
- Acute Ischemic Stroke
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 675 participants (actual)
- Lead sponsor
- Cerevast Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- May 2013
- Primary completion
- Apr 2015 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 6 Apr 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 is a randomized, placebo-controlled, phase 3 clinical trial to evaluate the efficacy and safety of transcranial ultrasound (US) as an adjunctive therapy to tissue plasminogen activator (tPA) treatment in subjects with acute ischemic stroke.
Detailed description
The primary objective of this trial is to provide information regarding the efficacy of a combined treatment with transcranial US and systemic tPA (Target group) compared to systemic tPA alone (Control group) in subjects with acute ischemic stroke. The primary efficacy endpoint is functional outcome at 3 months from stroke onset (modified Rankin Score ordinal shift analysis). The primary safety endpoint is the proportion of subjects in the Target vs Control group experiencing symptomatic intracranial hemorrhage (sICH) within 24 hours of treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Target group | Experimental | Device: Transcranial ultrasound as an adjunctive therapy to tPAA combined treatment with transcranial US and systemic tPA |
| Control group | Active comparator | Drug: Standard of care tPA therapy for acute ischemic strokeSystemic tPA alone |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Males or females 18 - 80 years of age
- Subjects presenting within timeframe for intravenous tPA treatment approved by local regulatory authorities but no more than 4.5 hours from onset of symptoms
- No signs of intracranial bleeding on assessment by non-contrast CT
- Subjects with neurological deficits of a total NIHSS score ≥ 10 points
- Subjects that in the opinion of the treating physician require treatment with full dose IV tPA as standard of care per institutional standards
Key exclusion criteria (5 listed)
- Subjects with primary intra-arterial thrombolysis
- Females who are pregnant or breast feeding
- Subjects receiving other investigational drugs, procedures, or therapies within 30 days prior to study treatment
- Subjects with any standard contraindication for intravenous tPA therapy
- Significant concurrent medical/neurological conditions or test values that, in the opinion of the investigator, pose significant risk to the subject and warrant exclusion from the study
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 |
|---|---|---|
| Transcranial ultrasound as an adjunctive therapy to tPA* tPA per approved labeling administered over 60 minutes * Ultrasonic headframe with active insonation for 120 minutes | Device | Target group |
| Standard of care tPA therapy for acute ischemic stroke* tPA per approved labeling administered over 60 minutes * Ultrasonic headframe with sham (inactive) insonation for 120 minutes | Drug | Control group |
Primary outcome
Modified Rankin score ordinal shift analysis
Time frame: 3 months
The primary objective of this study is to compare clinical recovery rates (modified Rankin score ordinal shift analysis) at 3 months after stroke onset.
1 secondary outcome
Symptomatic intracerebral hemorrhage
Time frame: 0-24 hours from treatment
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2015.
- Derived from this study: PubMed 30878103Alexandrov AV, Kohrmann M, Soinne L, Tsivgoulis G, Barreto AD, Demchuk AM, Sharma VK, Mikulik R, Muir KW, Brandt G, Alleman J, Grotta JC, Levi CR, Molina CA, Saqqur M, Mavridis D, Psaltopoulou T, Vosko M, Fiebach JB, Mandava P, Kent TA, Alexandrov AW, Schellinger PD; CLOTBUST-ER Trial Investigators. Safety and efficacy of sonothrombolysis for acute ischaemic stroke: a multicentre, double-blind, phase 3, randomised controlled trial. Lancet Neurol. 2019 Apr;18(4):338-347. doi: 10.1016/S1474-4422(19)30026-2.
- Derived from this study: PubMed 26120902Schellinger PD, Alexandrov AV, Barreto AD, Demchuk AM, Tsivgoulis G, Kohrmann M, Alleman J, Howard V, Howard G, Alexandrov AW, Brandt G, Molina CA; CLOTBUSTER Investigators. Combined lysis of thrombus with ultrasound and systemic tissue plasminogen activator for emergent revascularization in acute ischemic stroke (CLOTBUST-ER): design and methodology of a multinational phase 3 trial. Int J Stroke. 2015 Oct;10(7):1141-8. doi: 10.1111/ijs.12536. Epub 2015 Jun 29.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Transcranial ultrasound as an adjunctive therapy to tPA in people with Acute Ischemic Stroke, run by Cerevast Therapeutics, Inc. at 1 site 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 12 inclusion and 5 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: stopped early, as of the sponsor's last update on 7 Apr 2015. 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 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 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 was stopped early. Results are not available in the source record.
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?
Modified Rankin score ordinal shift analysis (time frame: 3 months). 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 NCT01098981, which also lists 2 linked publications.
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 7 Apr 2015.