Clinical trial NCT06485427: Safety and Efficacy of Selective Intra-Arterial Cooling Infusion Combined With EVT in Acute Ischemic Stroke
Official title: Safety and Efficacy of Selective Intra-Arterial Cooling Infusion Combined With Endovascular Thrombectomy in Acute Ischemic Stroke: A Multicenter, Randomized Controlled, Subject- and Assessor-Blind Clinical Trials
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Acute Ischemic Stroke
Hypothermia
Lead sponsor: Beijing Shijitan Hospital, Capital Medical University
Sponsor class: OTHER
First posted: 2024-07-03
Enrollment: 258
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multicenter, randomized, controlled, subject- and assessor-blinded clinical trial. The research objective is to evaluate the safety and efficacy of selective intra-arterial cooling infusion combined with endovascular therapy in the treatment of acute anterior circulation large vessel occlusion stroke. This trial aims to enroll 258 subjects. Patients assigned to the control group will receive best medical management (BMM) and endovascular therapy (EVT). Those in the selective intra-arterial cooling infusion group (IA-SCI group) will undergo selective intra-arterial cold saline infusion, in addition to BMM and EVT. Subjects will be interviewed face-to-face at randomization, 24±6 hours, 48±6 hours after randomization, 7±2 days/discharge. Telephone interviews/ face-to face interviews will be performed at 30±3 days and 90±7 days after randomization. The primary outcome is the distribution of Modified Rankin Score at 90±7days after randomization.

Detailed description: Acute ischemic stroke (AIS) is the leading cause of death and disability in China. Randomized trials involving patients with acute stroke due to large-artery occlusion in the anterior circulation have shown a benefit of endovascular therapy (EVT). Although EVT achieves successful recanalization in over 80% of patients, only 46% of patients are functionally independent (mRS 0-2) after the intervention . Therefore, new ancillary therapeutic strategies are needed to further improve the clinical outcomes.

Therapeutic systemic hypothermia has been suggested to be one such potential approach offering a viable neuroprotective strategy. However, several adverse events associated with the systematic hypothermia treatment have been reported. Those offset the therapeutic benefits of systemic hypothermia. Selective intra-arterial cooling infusion (IA-SCI) targets precisely the ischemic brain tissue with the infusion of hypothermic solutions. This approach induces a state of mild hypothermia in the ischemic region without causing substantial drops in core body temperature, thereby minimizing the incidence of systemic side effects. Previous studies have shown that IA-SCI with cold saline combined with EVT in AIS is safe and feasible.

Hence, the investigators design a multicenter, randomized, controlled, subject- and assessor-blinded clinical trial. The objective of this trial is to further explore the safety and efficacy of selective intra-arterial cooling infusion combined with EVT in the treatment of acute anterior circulation large vessel occlusion stroke, and 258 subjects will be enrolled. Subjects assigned to the control group will receive best medical management (BMM) and endovascular therapy (EVT). Those in the selective intra-arterial cooling infusion group (IA-SCI group) will undergo selective intra-arterial cold saline infusion, in addition to BMM and EVT. Subjects will be interviewed face-to-face at randomization, 24±6 hours, 48±6 hours after randomization, 7±2 days/discharge. Telephone interviews/ face-to face interviews will be performed at 30±3 days and 90±7 days after randomization. The primary outcome is the distribution of Modified Rankin Score at 90±7days after randomization.

Eligibility criteria: Inclusion Criteria

1. Age ≥ 18 and ≤ 80.
2. Clinical signs consistent with acute ischemic stroke with large vessel occlusion in the anterior circulation (intracranial segment of the internal carotid artery, middle cerebral artery M1 segment) demonstrated with CTA/MRA/DSA.
3. NIHSS score obtained prior to randomization ≥ 6 and ≤ 25.
4. Modified Rankin Scale ≤ 1 prior to qualifying stroke.
5. Arterial puncture performed within 24 hours from symptom onset or LKW.
6. For the patients with symptom onset within 6 hours, the ASPECT score ≥ 6; for the patients with onset within 6-24 hours, the therapy should meet the imaging criteria of DAWN or DEFUSE-3 trial.
7. Patient/Legally Authorized Representative has signed the Informed Consent Form.

Exclusion Criteria

1. Baseline CT/MRI confirms the presence of multiple vascular territory acute strokes.
2. Baseline CT/MRI confirms the presence of arterial dissection.
3. Evidence of intracranial hemorrhage or hemorrhagic transformation before thrombectomy.
4. Known allergies or intolerances to antiplatelet agents, anticoagulation drugs, iodinated contrast and/or anesthetics.
5. Severe infection (e.g. sepsis) or multiple organ failure.
6. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; recent oral anticoagulant therapy with INR \> 3. Patients on factor Xa inhibitor for 48 hours ago must have a normal APTT.
7. Baseline platelet count \< 50 × 10\^9/L.
8. Blood glucose concentration\<50 mg/dL (2.7 mmol/L) or \>400 mg/dL (22.2 mmol/L).
9. Refractory hypertension that is difficult to control by medication (Defined as persistent systolic blood pressure\>185 mmHg or diastolic blood pressure\>110 mmHg).
10. Previous NHYA\>1.
11. Untreated moderate or severe coronary artery stenosis, or previous coronary artery bypass surgery.
12. Undergoing hemodialysis or peritoneal dialysis; known severe renal insufficiency with glomerular filtration rate \< 30 mL/min or serum creatinine \>220 mmol/L (2.5 mg/dL).
13. Known intracranial aneurysm, and cerebral arteriovenous malformation.
14. Malignant brain tumor or CNS infection.
15. Pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations (e.g., dementia or mental illness)
16. Female who is pregnant or lactating at time of admission.
17. Anticipated life expectancy \< 6 months.
18. Current participation in another investigational drug or device study.
19. For other reasons, the responsible clinicians believe that the patient is not suitable for continued treatment.

Primary outcomes:
measure: Distribution of Modified Rankin scale
timeFrame: 90 ±7days
Secondary outcomes:
measure: Percentage of functional independence (mRS scale 0-2)
timeFrame: 90 ±7days
measure: Percentage of favorable outcome (mRS scale 0-1)
timeFrame: 90 ±7days
measure: Final infarction volume
timeFrame: 7±2 days/discharge
measure: The changes of infarction volume
timeFrame: 7±2 days/discharge
measure: National Institute of Health stroke scale (NIHSS) score
timeFrame: 7±2 days/discharge
measure: Barthel Index score
timeFrame: 7±2 days/discharge
measure: Rapid neurologic improvement
timeFrame: 24±12 hours
measure: Changes in ipsilateral tympanic membrane temperature
timeFrame: during surgery.
measure: Power spectral density (PSD) assessed by continuous electroencephalogram (EEG)
timeFrame: within 7±2 days/discharge
measure: (delta+theta)/(alpha+beta) power ratio (DTABR) assessed by continuous electroencephalogram (EEG)
timeFrame: within 7±2 days/discharge
measure: Delta/alpha power ratio (DAR) assessed by continuous electroencephalogram (EEG)
timeFrame: within 7±2 days/discharge
measure: Brain symmetry index (BSI) assessed by continuous electroencephalogram (EEG)
timeFrame: within 7±2 days/discharge
measure: Symptomatic intracranial hemorrhage
timeFrame: 24±12 hours
measure: Any intracranial hemorrhage
timeFrame: 24±12 hours
measure: Intracranial arterial vasospasm after IA-SCI that requires further therapeutic intervention.
timeFrame: during operation
measure: Proportion of subjects with pulmonary, urinary tract infection and gastroenteritis
timeFrame: 7±2 days/discharge
measure: Proportion of subjects with coagulation abnormalities
timeFrame: 24±12 hours
measure: Proportion of subjects with electrolyte imbalance
timeFrame: 24±12 hours
measure: Changes in core temperature before and after intra-arterial cooling infusion in the IA-SCI group.
timeFrame: During operation
measure: any death
timeFrame: 90±7 days
measure: other AE/SAE
timeFrame: 90±7 days
Other outcomes:
Locations:
city: Lanzhou
country: China
facility: The Second Hospital and Clinical Medical School, Lanzhou University
state: Gan Su
city: Nanyang
country: China
facility: Department of Neurosurgery, Nanshi Hospital of Nanyang
state: He Nan
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
state: Jiang Su
city: Beijing
country: China
facility: Beijing Shijitan Hospital, Capital Medical University
city: Beijing
country: China
facility: Peking University Internation Hospital
city: Dalian
country: China
facility: 967 Hospital of the Joint Logistics Support Force of PLA
city: Dalian
country: China
facility: Dalian Municipal Central Hospital
city: Ha'erbin
country: China
facility: The First Affiliated Hospital of Harbin Medical University
city: Tongliao
country: China
facility: Affiliated Hospital of Inner Mongolia University for the Nationalities
Study officials:
affiliation: Beijing Shijitan Hospital, Capital Medical University
name: Shen Li
role: PRINCIPAL_INVESTIGATOR
References: