HypothermiaPhase 2/3NCT03163459
Short-duration Selective Brain Cooling for Patients Undergoing Mechanical Thrombectomy
A Phase 2/3 study testing selective brain cooling by cold saline perfusion and mechanical thrombectomy in people with Hypothermia and Stroke, Acute, run by Capital Medical University at 1 site in China.
Trial summary
To determine the efficacy and safety of short-duration intra-artery selective brain cooling in addition to mechanical thrombectomy in patients with acute ischemic stroke. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hypothermia, Stroke, Acute
- What is being tested?
- selective brain cooling by cold saline perfusion and mechanical thrombectomy
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteChina
- Study dates
- 6 Feb 2018to 16 Dec 2020
- Phase
- Phase 2/3
- 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
- Acute ischemic stroke within 6 hours from symptom onset/last seen well.
- Occlusion (TIMI 0-1) of the basilar artery or distal intracranial carotid artery or middle (M1/M2) or anterior (A1/A2) cerebral artery as evidenced by CTA/MRA/DSA.
- Age ≥18 and ≤80
- No significant pre-stroke functional disability (mRS ≤ 1)
- The possibility to start treatment within 6 hours from onset.
- Informed consent given
Who cannot join
- Known hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR > 3.0
- Baseline platelet count < 50.000/µL
- Baseline blood glucose of < 50mg/dL or >400mg/dl
- Severe, sustained hypertension (SBP > 220 mm Hg or DBP > 110 mm Hg) NOTE: If the blood pressure can be successfully reduced and maintained below these levels using commonly used medications in China for these purposes (including iv antihypertensive drips), the patient can be enrolled.
- Serious, advanced, or terminal illness with anticipated life expectancy of less than one year.
- History of life threatening allergy (more than rash) to contrast medium
Show all 15Show fewer
- Subjects who has received iv t-PA treatment beyond 4.5 hours from the beginning of the symptoms.
- Patients with acute stroke within the first 48 hours after percutaneous cardiac, cerebrovascular interventions and major surgery
- Renal insufficiency with creatinine ≥ 3 mg/dl
- Woman of childbearing potential who is known to be pregnant or lactating or who has a positive pregnancy test on admission.
- Subject participating in a study involving an investigational drug or device that would impact this study.
- Cerebral vasculitis
- Patients with a pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations, mRS score at baseline must be ≤ 1, which includes patients who are severely demented, require constant assistance in a nursing home type setting or who live at home but are not fully independent in activities of daily living (toileting, dressing, eating, cooking and preparing meals, etc.)
- Unlikely to be available for 90 days follow-up (e.g. no fixed home address, visitor from overseas).
- CT or MR evidence of hemorrhage (the presence of microbleeds on MRI is allowed).
Trial locations and contacts
1 site in 1 country.
China1 site
Xuan Wu Hospital，Capital Medical University
Beijing, Beijing Municipality, 100069
About this study
Official title: Short-duration Selective Brain Cooling for Ischemic Stroke Patients Undergoing Mechanical Thrombectomy: a Randomized Controlled Trial
To determine the efficacy and safety of short-duration intra-artery selective brain cooling in addition to mechanical thrombectomy in patients with acute ischemic stroke.
Read the detailed description
Acute ischemic stroke remains one of the leading causes of disability and death in both developed and developing countries. Using intravenous thrombolysis combined with intra-arterial therapy to recanalize occluded vessels in eligible patients is recommended by current guidelines. Five randomized clinical trials showed that modified thrombolysis in cerebral ischemia (mTICI) 2b/3 recanalization can be achieved in 59-88% of acute ischemic stroke patients with anterior circulation large artery occlusion，but only an average of 46% of patients have a favorable outcome (modified Rankin Scale score [mRS] 0-2). Therefore, new therapeutic strategies in addition to thrombectomy for acute ischemic stroke are urgently needed.
As early as 1987, Busto et al. found that lowering of the brain temperature by only a few degrees during ischemia confers a marked neuroprotective effect. Therapeutic hypothermia has been suggested to be the most potent neuroprotective strategy in recent years5，and a number of clinical studies in patients with acute cerebral infarction also showed that mild hypothermia (33-35 ℃) can increase tolerance to ischemic insults and play a significant neuroprotective role after reperfusion. However, adverse events such as pneumonia, affecting up to 35% of treated patients occurs with hypothermia. Since selective brain cooling does not require a reduction in core body temperature, it is theoretically possible to avoid many serious adverse effects caused by whole body hypothermia.
The investigators have previous shown that short-duration selective brain cooling by the intra-arterial infusion of cold saline combined with mechanical thrombectomy in acute ischemic stroke is feasible and safe. The efficacy of selective brain cooling in patients undergoing mechanical thrombectomy, however, is not established. The investigators therefore conducted this RCT study to explore the efficacy of short-duration selective brain cooling in patients with acute ischemic stroke who underwent mechanical thrombectomy.
- Conditions
- Hypothermia, Stroke, Acute
- Being tested
- selective brain cooling by cold saline perfusion, mechanical thrombectomy
- Keywords
- mechanical thrombectomy, selective brain cooling
- Medical subject headings
- Hypothermia, Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
selective brain cooling by cold saline perfusionDrug
During the procedure, a microcatheter which was used to deploy the stent retriever was threaded into the femoral artery in the groin through a guiding catheter and up through the neck, until it reached beyond the clot causing the stroke under the assistance of micro-guide wire, 50 mL cold 0.9% saline (4°C) was infused into the ischemic territory at 10 mL/min through the microcatheter, thus allowing the cold solution to infuse into the ischemic territory prior to reperfusion. After that, mechanical thrombectomy with a stent retriever was performed to recanalize the occluded vessel as soon as possible. After the recanalization, cold 0.9% saline (4°C) was infused into the ischemic brain tissue through the guide catheter at 30 mL/min for 10 minutes.
mechanical thrombectomyDevice
conventional mechanical thrombectomy using Solitaire
| Study group | Role | What they receive |
|---|---|---|
| mechanical thrombectomy group | Active comparator | Conventional mechanical thrombectomy Receives: Device: mechanical thrombectomy |
| mechanical thrombectomy plus selective brain cooling group | Experimental | A microcatheter which was used to deploy the stent retriever was threaded into the femoral artery in the groin through a guiding catheter and up through the neck, until it reached beyond the clot causing the stroke under the assistance of micro-guide wire, 50 mL cold 0.9% saline (4°C) was infused into the ischemic territory at 10 mL/min through the microcatheter, thus allowing the cold solution to infuse into the ischemic territory prior to reperfusion. After that, mechanical thrombectomy with a stent retriever was performed to recanalize the occluded vessel as soon as possible. After the recanalization, cold 0.9% saline (4°C) was infused into the ischemic brain tissue through the guide catheter at 30 mL/min for 10 minutes. Receives: Drug: selective brain cooling by cold saline perfusion; Device: mechanical thrombectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients achieving favorable outcomes defined as mRS 0-2 at 90 days as evaluated by independent central assessors who are blinded to treatment
mRS 0-2
Measured: 90 days
Secondary outcomes (8)
Dramatic early favorable response
an NIHSS of 0-2 or NIHSS improvement ≥ 8 points at 24 (-2/+12 hours) hours from randomization or before discharge if patient is discharged prior to the above time limit
Measured: 24 hours
Final infarct volume evaluated on CT/MR at 24 hours (-2/+12 hours)
Final infarct volume evaluated on CT/MR at 24 hours (-2/+12 hours)
Measured: 24 hours
The change of infarct volume compared with baseline.
The change of infarct volume compared with baseline.
Measured: 24 hours
Vessel recanalization
Vessel recanalization evaluated by angiography (one of CT angiography , MR Angiography and conventional angiography) at 24 hours (-2/+12 hours) in both treatment groups
Measured: 24 hours
Barthel Index at 90 days
Barthel Index at 90 days
Measured: 90 days
NIHSS at 90 days
NIHSS at 90 days
Measured: 90 days
Proportion of patients achieving excellent favorable outcomes defined as mRS 0-1 at 90 days
mRS 0-1 at 90 days
Measured: 90 days
mRS shift analysis at 90 days
mRS shift analysis
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 posted23 May 2017
- Study start6 Feb 2018
- Primary completion30 Sep 2020 (estimated)
- Study completion16 Dec 2020 (estimated)
Why it stopped: Interim analysis
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypothermiaStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Capital Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ji Xunming,MD,PhD, Capital Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03163459
- Sponsor's protocol ID
- ET-EH
- Status last verified
- Aug 2020
- First submitted
- 6 May 2017
- Last updated
- 4 Aug 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Chen J, Liu L, Zhang H, Geng X, Jiao L, Li G, Coutinho JM, Ding Y, Liebeskind DS, Ji X. Endovascular Hypothermia in Acute Ischemic Stroke: Pilot Study of Selective Intra-Arterial Cold Saline Infusion. Stroke. 2016 Jul;47(7):1933-5. doi: 10.1161/STROKEAHA.116.012727. Epub 2016 May 19.
PubMed 27197848
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Short-duration Selective Brain Cooling for Ischemic Stroke Patients Undergoing Mechanical Thrombectomy: a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03163459
- Acronym / sponsor ID
- ET-EH
- Conditions
- Hypothermia, Stroke, Acute
- Keywords
- mechanical thrombectomy, selective brain cooling
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Interim analysis
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Capital Medical UniversityUniversity, hospital or other
- Study start
- 6 Feb 2018 (actual)
- Primary completion
- 30 Sep 2020 (estimated)
- Study completion
- 16 Dec 2020 (estimated)
- First posted
- 23 May 2017 (actual)
- 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.
To determine the efficacy and safety of short-duration intra-artery selective brain cooling in addition to mechanical thrombectomy in patients with acute ischemic stroke.
Detailed description
Acute ischemic stroke remains one of the leading causes of disability and death in both developed and developing countries. Using intravenous thrombolysis combined with intra-arterial therapy to recanalize occluded vessels in eligible patients is recommended by current guidelines. Five randomized clinical trials showed that modified thrombolysis in cerebral ischemia (mTICI) 2b/3 recanalization can be achieved in 59-88% of acute ischemic stroke patients with anterior circulation large artery occlusion，but only an average of 46% of patients have a favorable outcome (modified Rankin Scale score [mRS] 0-2). Therefore, new therapeutic strategies in addition to thrombectomy for acute ischemic stroke are urgently needed.
As early as 1987, Busto et al. found that lowering of the brain temperature by only a few degrees during ischemia confers a marked neuroprotective effect. Therapeutic hypothermia has been suggested to be the most potent neuroprotective strategy in recent years5，and a number of clinical studies in patients with acute cerebral infarction also showed that mild hypothermia (33-35 ℃) can increase tolerance to ischemic insults and play a significant neuroprotective role after reperfusion. However, adverse events such as pneumonia, affecting up to 35% of treated patients occurs with hypothermia. Since selective brain cooling does not require a reduction in core body temperature, it is theoretically possible to avoid many serious adverse effects caused by whole body hypothermia.
The investigators have previous shown that short-duration selective brain cooling by the intra-arterial infusion of cold saline combined with mechanical thrombectomy in acute ischemic stroke is feasible and safe. The efficacy of selective brain cooling in patients undergoing mechanical thrombectomy, however, is not established. The investigators therefore conducted this RCT study to explore the efficacy of short-duration selective brain cooling in patients with acute ischemic stroke who underwent mechanical thrombectomy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| mechanical thrombectomy group | Active comparator | Device: mechanical thrombectomyConventional mechanical thrombectomy |
| mechanical thrombectomy plus selective brain cooling group | Experimental | Drug: selective brain cooling by cold saline perfusion, Device: mechanical thrombectomyA microcatheter which was used to deploy the stent retriever was threaded into the femoral artery in the groin through a guiding catheter and up through the neck, until it reached beyond the clot causing the stroke under the assistance of micro-guide wire, 50 mL cold 0.9% saline (4°C) was infused into the ischemic territory at 10 mL/min through the microcatheter, thus allowing the cold solution to infuse into the ischemic territory prior to reperfusion. After that, mechanical thrombectomy with a stent retriever was performed to recanalize the occluded vessel as soon as possible. After the recanalization, cold 0.9% saline (4°C) was infused into the ischemic brain tissue through the guide catheter at 30 mL/min for 10 minutes. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Acute ischemic stroke within 6 hours from symptom onset/last seen well.
- Occlusion (TIMI 0-1) of the basilar artery or distal intracranial carotid artery or middle (M1/M2) or anterior (A1/A2) cerebral artery as evidenced by CTA/MRA/DSA.
- Age ≥18 and ≤80
- No significant pre-stroke functional disability (mRS ≤ 1)
- The possibility to start treatment within 6 hours from onset.
Key exclusion criteria (15 listed)
- Known hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR > 3.0
- Baseline platelet count < 50.000/µL
- Baseline blood glucose of < 50mg/dL or >400mg/dl
- Severe, sustained hypertension (SBP > 220 mm Hg or DBP > 110 mm Hg) NOTE: If the blood pressure can be successfully reduced and maintained below these levels using commonly used medications in China for these purposes (including iv antihypertensive drips), the patient can be enrolled.
- Serious, advanced, or terminal illness with anticipated life expectancy of less than one year.
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 |
|---|---|---|
| selective brain cooling by cold saline perfusionDuring the procedure, a microcatheter which was used to deploy the stent retriever was threaded into the femoral artery in the groin through a guiding catheter and up through the neck, until it reached beyond the clot causing the stroke under the assistance of micro-guide wire, 50 mL cold 0.9% saline (4°C) was infused into the ischemic territory at 10 mL/min through the microcatheter, thus allowing the cold solution to infuse into the ischemic territory prior to reperfusion. After that, mechanical thrombectomy with a stent retriever was performed to recanalize the occluded vessel as soon as possible. After the recanalization, cold 0.9% saline (4°C) was infused into the ischemic brain tissue through the guide catheter at 30 mL/min for 10 minutes. | Drug | mechanical thrombectomy plus selective brain cooling group |
| mechanical thrombectomyconventional mechanical thrombectomy using Solitaire | Device | mechanical thrombectomy group, mechanical thrombectomy plus selective brain cooling group |
Primary outcome
Proportion of patients achieving favorable outcomes defined as mRS 0-2 at 90 days as evaluated by independent central assessors who are blinded to treatment
Time frame: 90 days
mRS 0-2
8 secondary outcomes
Dramatic early favorable response
Time frame: 24 hours
Final infarct volume evaluated on CT/MR at 24 hours (-2/+12 hours)
Time frame: 24 hours
The change of infarct volume compared with baseline.
Time frame: 24 hours
Vessel recanalization
Time frame: 24 hours
Barthel Index at 90 days
Time frame: 90 days
NIHSS at 90 days
Time frame: 90 days
Proportion of patients achieving excellent favorable outcomes defined as mRS 0-1 at 90 days
Time frame: 90 days
mRS shift analysis at 90 days
Time frame: 90 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2020.
- Background: PubMed 27197848Chen J, Liu L, Zhang H, Geng X, Jiao L, Li G, Coutinho JM, Ding Y, Liebeskind DS, Ji X. Endovascular Hypothermia in Acute Ischemic Stroke: Pilot Study of Selective Intra-Arterial Cold Saline Infusion. Stroke. 2016 Jul;47(7):1933-5. doi: 10.1161/STROKEAHA.116.012727. Epub 2016 May 19.
- 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.
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 2/3 study testing selective brain cooling by cold saline perfusion and mechanical thrombectomy in people with Hypothermia and Stroke, Acute, run by Capital Medical University at 1 site in China.
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 15 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: paused, as of the sponsor's last update on 4 Aug 2020. 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 China. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
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?
Proportion of patients achieving favorable outcomes defined as mRS 0-2 at 90 days as evaluated by independent central assessors who are blinded to treatment (time frame: 90 days). 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 NCT03163459, 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 4 Aug 2020.