StrokePhase 1CUFFSNCT00983749
Safety Study of External Counterpulsation as a Treatment for Acute Ischemic Stroke
A Phase 1 study testing Full-pressure ECP in people with Stroke, run by University of California, San Diego at 3 sites in United States.
Trial summary
The purpose of this study is to determine if external counterpulsation (ECP) is feasible to perform, tolerable, and safe as a treatment for patients with acute ischemic stroke (i.e., a blockage of one of the arteries supplying a part of the brain), and to assess what type of effect it might have on 1) the velocity of… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Stroke
- What is being tested?
- Full-pressure ECP
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 3 sitesUnited States
- Study dates
- Dec 2009to Jul 2013
- Phase
- Phase 1
- 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
- Adults between the ages of 18 and 85, inclusive
- Symptoms consistent with acute ischemic stroke, with a measurable neurological deficit at presentation
- Ability to initiate external counterpulsation within 48 hours of stroke onset
- No evidence of hemorrhage on CT scan or MRI
- MCA distribution stroke: a total or partial anterior circulation infarct (TACI or PACI by Oxfordshire criteria) consistent with MCA distribution ischemia, or a lacunar stroke felt by the investigator to possibly involve a deep perforating branch in the MCA territory (LACI by Oxfordshire criteria)
Who cannot join
- Rapidly resolving stroke symptoms consistent with a transient ischemic attack
- Severe stroke defined as an NIHSS > 22
- Intracranial hemorrhage (SAH, EDH, SDH, IPH, hemorrhagic conversion) on CT scan
- Brain tumor or brain abscess on CT scan or MRI
- Presentation consistent with subarachnoid hemorrhage (such as a sudden, severe thunderclap headache, or an associated third nerve palsy)
- History of cerebral aneurysm, AVM, or hemorrhagic stroke
Show all 27Show fewer
- Either treatment or planned treatment of current stroke with standard thrombolytic therapy (intravenous or intra-arterial) or neurothrombectomy
- History of lower limb amputation above the ankle
- History of untreated aortic dissection
- History or suspicion of thoracic or abdominal aortic aneurysm
- Known significant anomaly of the heart, aorta, or great vessels that would be complicated by elevated diastolic pressures.
- BP > 180/100 that remains so after minimal treatment (such as one or two doses of an antihypertensive agent, or as determined by the investigator)
- History of non-trivial aortic regurgitation, or any symptomatic valvular heart disease determined by the investigator to be at risk of worsening on ECP
- Significant symptomatic congestive heart failure (orthopnea, CHF-related dyspnea, or rales and jugular venous distention on exam) or a left ventricular ejection fraction known to be <30%
- Diagnosis of significant lower extremity peripheral vascular occlusive disease (PVOD), or symptomatic PVOD as determined by the investigator (especially symptoms of claudication)
- Phlebitis, stasis ulcer, severe varicosities
- Diagnosis of DVT within the past month, or current symptoms strongly suggestive of new DVT, such as asymmetric calf or leg swelling, discomfort, or erythema (to be evaluated by screening duplex)
- Pacemaker or automated implanted defibrillator (AICD)
- A cardiac dysrhythmia (such as atrial fibrillation or atrial flutter, or frequent premature ventricular contractions (PVCs) or premature atrial contractions (PACs) as determined by the investigator) that would interfere with ECP triggering
- Pregnancy (as determined by a urine pregnancy test in females of child-bearing age)
- Known coagulopathy, thrombocytopenia with platelet count < 100,000, or taking warfarin with an INR > 2.0.
- History positive for chronic low back pain, radiculopathy suggestive of herniated lumbar disc, or related surgery
- Known collagen vascular disease
- Obesity to a degree (as determined by the investigator) that would prevent proper placement and/or activation of counterpulsation cuffs
- Any psychological, social, or legal condition that would interfere with the ability of the patient or his or her surrogate to give Informed Consent and/or his or her capacity to comply with all study requirements, including the necessary time commitment
- An inadequate temporal window for TCD insonation.
- Currently involved or have been involved in a clinical trial within the last 30 days.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Alabama Hospital
Birmingham, Alabama, 35249
UCLA Medical Center
Los Angeles, California, 90095
UCSD Medical Center
San Diego, California, 92103
About this study
Official title: A Randomized, Controlled Phase 1 Study of External Counterpulsation as a Treatment for Acute Ischemic Stroke
The purpose of this study is to determine if external counterpulsation (ECP) is feasible to perform, tolerable, and safe as a treatment for patients with acute ischemic stroke (i.e., a blockage of one of the arteries supplying a part of the brain), and to assess what type of effect it might have on 1) the velocity of blood flow in the arteries supplying the brain and 2) stroke symptoms. The hypothesis of the study is that ECP will be feasible and safe to perform, and will be tolerable for patients with acute ischemic stroke at pressures that increase the velocity of arterial blood flow to the brain.
Read the detailed description
A stroke is usually caused by a blockage of one of the arteries that carries blood to the brain. Sometimes with a stroke, there may be a small amount of blood flow that manages to get through or around the blockage, and it may be possible that the amount of damage from a stroke may be reduced by increasing this blood flow. External counterpulsation (ECP) is a procedure in which a machine uses electrical signals from the heart that are detectable on the surface of the body in order to time the inflation of cuffs (similar to a blood pressure cuff) that are wrapped around a patient's legs (calves, thighs and buttocks). Using a reading of the electrical activity from the patient's heart (an electrocardiogram, or ECG, monitor), the machine inflates the cuffs with air at just the right time during each heart beat, during diastole, in order to change the blood pressure in a way that has been shown to increase blood flow to the kidneys, skin, eyes, heart, and brain.
In this study, patients presenting within the first 48 hours of an acute ischemic stroke (i.e., a blockage of one of the arteries supplying a part of the brain) will be randomly assigned to either of (1) a 1-hour treatment of external counterpulsation (ECP) applied at a pressure that is typically therapeutic, or (2) a 1-hour treatment of ECP at a minimal pressure in a control group. ECP-induced changes in brain artery flow velocity will be assessed with an ultrasound prior to and then during ECP in each group, and an optimal pressure that results in an augmentation of flow velocity will be determined. A neurological exam will be performed prior to, during, and after ECP in each group, in order to assess any changes in stroke symptoms related to ECP. Patients will be followed to 30 days. The main goal of this trial is to evaluate if ECP is safe and feasible to use as a treatment for stroke. In addition, the trial will enable an assessment of whether or not ECP increases blood flow to the brain or affects the neurological symptoms of a patient with a stroke.
- Conditions
- Stroke
- Being tested
- Full-pressure ECP, Sham-pressure ECP
- Keywords
- External Counterpulsation, Counterpulsation, Diastolic, Ultrasonography, Doppler, Transcranial, Blood Flow Velocity, Neurologic Deficit
- Medical subject headings
- Stroke, Heart Murmurs, Neurologic Manifestations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Full-pressure ECPDevice
Also called External counterpulsation
A one-hour treatment of ECP at full pressure, which will be applied in a tiered, dose-escalating manner, starting at 200mmHg and increasing up to 300mmHg based on assessments made.
Sham-pressure ECPDevice
Also called External counterpulsation
A one-hour treatment of ECP at an inactive pressure, which will be applied at 75mmHg and kept there for the hour while assessments are made.
| Study group | Role | What they receive |
|---|---|---|
| Full-pressure ECP | Experimental | Patients in the "Full-pressure ECP" arm receive a 1-hour treatment of ECP at full pressure, which will be applied in a tiered, dose-escalating manner up to 300mmHg, while assessments are made. Receives: Device: Full-pressure ECP |
| Sham-pressure ECP | Sham comparator | A 1-hour treatment of ECP at an inactive pressure (75mmHg) Receives: Device: Sham-pressure ECP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility and Tolerability of External Counterpulsation
The first primary outcome measure was tolerability and feasibility. Tolerance was defined as the absence of any indications to stop the procedure or reduce the pressure to a non-therapeutic level. Feasibility was defined in the full-pressure group as the sustained (at least 30 minutes) tolerance of any pressure capable of causing a 15% augmentation of MFV in 90% of subjects, and defined in the sham-pressure group as the sustained tolerance of the sham pressure in all subjects.
Measured: During one hour of treatment
Safety (Including Endpoints Such an Increase NIHSS During or Immediately After ECP, and Acute Hemorrhage on Repeating Imaging, Serious Adverse Events Related to ECP, Mortality)
Safety was evaluated by the incidence of serious adverse events (SAEs) or acute neurological deterioration in relation to the study device and/or procedures at 30 days, the incidence of acute symptomatic hemorrhage on repeat imaging at 24 hours, the incidence of all adverse events (AEs) in the first 48 hours, and mortality at 30 days. The National Institutes of Health Stroke Scale (NIHSS) is a stroke severity scale, based on examination, that goes from 0 (no deficit) to a maximum of 42. Acute neurological deterioration - which was captured as a serious adverse event - was defined as a ≥4-point increase on the NIHSS, or a ≥2-point decline in level of consciousness item 1a on the NIHSS, or a new neurological deficit, or clinically significant worsening of motor function lasting more than 8 hours and attributable to a neurological entity. Symptomatic intracranial hemorrhage was defined as new hemorrhage on CT that was associated with acute neurological deterioration.
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2009 (estimated)
- Study startDec 2009
- Primary completionFeb 2013
- Study completionJul 2013
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.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- University of Alabama at Birmingham, University of California, Los Angeles, National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Principal investigator, Kama Guluma, University of California, San Diego
- Investigators
- Kama Z Guluma, M.D., Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00983749
- Sponsor's protocol ID
- SPOTRIAS Project 1
- Other IDs
- 3P50NS044148-06S1
- Acronym
- CUFFS
- Status last verified
- May 2016
- First submitted
- 23 Sep 2009
- Last updated
- 28 Jun 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Controlled Phase 1 Study of External Counterpulsation as a Treatment for Acute Ischemic Stroke
- ClinicalTrials.gov ID
- NCT00983749
- Acronym / sponsor ID
- CUFFS / SPOTRIAS Project 1
- Conditions
- Stroke
- Keywords
- External Counterpulsation, Counterpulsation, Diastolic, Ultrasonography, Doppler, Transcranial, Blood Flow Velocity, Neurologic Deficit
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- University of Alabama at Birmingham, University of California, Los Angeles, National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Dec 2009
- Primary completion
- Feb 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 24 Sep 2009 (estimated)
- Results
- Posted 28 Jun 2016
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 study is to determine if external counterpulsation (ECP) is feasible to perform, tolerable, and safe as a treatment for patients with acute ischemic stroke (i.e., a blockage of one of the arteries supplying a part of the brain), and to assess what type of effect it might have on 1) the velocity of blood flow in the arteries supplying the brain and 2) stroke symptoms. The hypothesis of the study is that ECP will be feasible and safe to perform, and will be tolerable for patients with acute ischemic stroke at pressures that increase the velocity of arterial blood flow to the brain.
Detailed description
A stroke is usually caused by a blockage of one of the arteries that carries blood to the brain. Sometimes with a stroke, there may be a small amount of blood flow that manages to get through or around the blockage, and it may be possible that the amount of damage from a stroke may be reduced by increasing this blood flow. External counterpulsation (ECP) is a procedure in which a machine uses electrical signals from the heart that are detectable on the surface of the body in order to time the inflation of cuffs (similar to a blood pressure cuff) that are wrapped around a patient's legs (calves, thighs and buttocks). Using a reading of the electrical activity from the patient's heart (an electrocardiogram, or ECG, monitor), the machine inflates the cuffs with air at just the right time during each heart beat, during diastole, in order to change the blood pressure in a way that has been shown to increase blood flow to the kidneys, skin, eyes, heart, and brain.
In this study, patients presenting within the first 48 hours of an acute ischemic stroke (i.e., a blockage of one of the arteries supplying a part of the brain) will be randomly assigned to either of (1) a 1-hour treatment of external counterpulsation (ECP) applied at a pressure that is typically therapeutic, or (2) a 1-hour treatment of ECP at a minimal pressure in a control group. ECP-induced changes in brain artery flow velocity will be assessed with an ultrasound prior to and then during ECP in each group, and an optimal pressure that results in an augmentation of flow velocity will be determined. A neurological exam will be performed prior to, during, and after ECP in each group, in order to assess any changes in stroke symptoms related to ECP. Patients will be followed to 30 days. The main goal of this trial is to evaluate if ECP is safe and feasible to use as a treatment for stroke. In addition, the trial will enable an assessment of whether or not ECP increases blood flow to the brain or affects the neurological symptoms of a patient with a stroke.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Full-pressure ECP | Experimental | Device: Full-pressure ECPPatients in the "Full-pressure ECP" arm receive a 1-hour treatment of ECP at full pressure, which will be applied in a tiered, dose-escalating manner up to 300mmHg, while assessments are made. |
| Sham-pressure ECP | Sham comparator | Device: Sham-pressure ECPA 1-hour treatment of ECP at an inactive pressure (75mmHg) |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adults between the ages of 18 and 85, inclusive
- Symptoms consistent with acute ischemic stroke, with a measurable neurological deficit at presentation
- Ability to initiate external counterpulsation within 48 hours of stroke onset
- No evidence of hemorrhage on CT scan or MRI
- MCA distribution stroke: a total or partial anterior circulation infarct (TACI or PACI by Oxfordshire criteria) consistent with MCA distribution ischemia, or a lacunar stroke felt by the investigator to possibly involve a deep perforating branch in the MCA territory (LACI by Oxfordshire criteria)
Key exclusion criteria (27 listed)
- Rapidly resolving stroke symptoms consistent with a transient ischemic attack
- Severe stroke defined as an NIHSS > 22
- Intracranial hemorrhage (SAH, EDH, SDH, IPH, hemorrhagic conversion) on CT scan
- Brain tumor or brain abscess on CT scan or MRI
- Presentation consistent with subarachnoid hemorrhage (such as a sudden, severe thunderclap headache, or an associated third nerve palsy)
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 |
|---|---|---|
| Full-pressure ECPAlso: External counterpulsationA one-hour treatment of ECP at full pressure, which will be applied in a tiered, dose-escalating manner, starting at 200mmHg and increasing up to 300mmHg based on assessments made. | Device | Full-pressure ECP |
| Sham-pressure ECPAlso: External counterpulsationA one-hour treatment of ECP at an inactive pressure, which will be applied at 75mmHg and kept there for the hour while assessments are made. | Device | Sham-pressure ECP |
Primary outcome
Feasibility and Tolerability of External Counterpulsation
Time frame: During one hour of treatment
The first primary outcome measure was tolerability and feasibility. Tolerance was defined as the absence of any indications to stop the procedure or reduce the pressure to a non-therapeutic level. Feasibility was defined in the full-pressure group as the sustained (at least 30 minutes) tolerance of any pressure capable of causing a 15% augmentation of MFV in 90% of subjects, and defined in the sham-pressure group as the sustained tolerance of the sham pressure in all subjects.
Safety (Including Endpoints Such an Increase NIHSS During or Immediately After ECP, and Acute Hemorrhage on Repeating Imaging, Serious Adverse Events Related to ECP, Mortality)
Time frame: 30 days
Safety was evaluated by the incidence of serious adverse events (SAEs) or acute neurological deterioration in relation to the study device and/or procedures at 30 days, the incidence of acute symptomatic hemorrhage on repeat imaging at 24 hours, the incidence of all adverse events (AEs) in the first 48 hours, and mortality at 30 days. The National Institutes of Health Stroke Scale (NIHSS) is a stroke severity scale, based on examination, that goes from 0 (no deficit) to a maximum of 42. Acute neurological deterioration - which was captured as a serious adverse event - was defined as a ≥4-point increase on the NIHSS, or a ≥2-point decline in level of consciousness item 1a on the NIHSS, or a new neurological deficit, or clinically significant worsening of motor function lasting more than 8 hours and attributable to a neurological entity. Symptomatic intracranial hemorrhage was defined as new hemorrhage on CT that was associated with acute neurological deterioration.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Kama Z Guluma, M.D. principal investigator
University of California, San Diego
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Full-pressure ECP in people with Stroke, run by University of California, San Diego at 3 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 27 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 28 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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. 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 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.
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 28 Jun 2016). 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?
Feasibility and Tolerability of External Counterpulsation (time frame: During one hour of treatment). 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?
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 28 Jun 2016.