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Low-Frequency REpetitive TRanscranial Magnetic Stimulation Combined With Endovascular Treatment in ACute Ischemic StrokE

Not Applicable
Not yet recruiting
Conditions
Stroke, Acute Ischemic
Interventions
Device: Sham stimulation
Device: LF-rTMS
Registration Number
NCT06064747
Lead Sponsor
Beijing Tiantan Hospital
Brief Summary

This is a multicenter, randomized, double-blind, sham-controlled, investigator-initiated clinical study, to evaluate the clinical efficacy and safety of LF-rTMS in rescuing the ischemic penumbra, reducing disability rate and improving functional outcome in patients with acute ischemic stroke receiving early endovascular recanalization (bridging or direct endovascular therapy)

Detailed Description

The target population of this study was patients with acute ischemic stroke of the anterior circulation diagnosed clinically. The site of acute occlusion of the responsible vessel was located in the intracranial segment of the internal carotid artery, T-type bifurcation or M1 segment of the middle cerebral artery, planning for bridging therapy (bridging intravascular therapy after intravenous thrombolysis with alteplase) or direct intravascular therapy, the time from stroke onset to the start of the trial intervention was less than 24 hours (when the exact time of onset was unknown, the patient's"Last apparent normal time" was defined as the time of onset).

Enrolled patients were randomly assigned in a 1:1 ratio to the"LF-rTMS group" or the"Sham Stimulation Group" and received:

1. LF-rTMS group: using "8" coil,1-Hz rTMS to stimulate the M1 region of the ipsilateral hemisphere, the stimulation intensity was RMT 100%, 1200pulses/session, two sessions (2400 pulses)/day (interval ≥ 2 hours), lasting 3 days (total 6 sessions, 7200pulses);

2. Sham stimulation group: the sham stimulation coil was used to stimulate the same site, duration and sound as the LF-rTMS group, ensuring no effective stimulation, twice a day for 3 days.

All patients received endovascular therapy (bridging therapy or direct endovascular therapy).

All patients were followed up until the 90th day after randomization to evaluate the clinical efficacy and safety of LF-rTMS in rescuing the ischemic penumbra, reducing disability rate and improving functional outcome in patients with acute ischemic stroke receiving early endovascular recanalization (bridging or direct endovascular therapy)

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
60
Inclusion Criteria
  1. 18 - 80 years, male or female;

  2. Clinically diagnosed as acute anterior ischemic stroke, artery occlusion occurred at the terminal of the intracranial carotid artery, T-shaped bifurcation or M1 segment of the middle cerebral artery;

  3. Within 24 hours of stroke onset;

  4. Eligible for other imaging indications for bridging therapy or direct mechanical thrombectomy:

    ASPECTS ≥6 certified by the latest brain CT imaging; Patients within 6-16 hours after stroke onset should meet the mismatch criteria, which was defined as infarction core volume <70 ml, mismatch ratio ≥1.8 and the ischemic volume > 15 ml (DEFUSE-3 Criteria); or NIHSS score ≥ 10 with infarction -core volume < 31 cm3, or NIHSS score ≥ 20 with infarction core volume ≤ 51 cm3 (DAWN Criteria); Patients within 16-24 hours after stroke onset should meet the mismatch criteria, which was defined as NIHSS score ≥ 10 with infarction-core volume < 31 cm3, or NIHSS score ≥ 20 with infarction-core volume ≤ 51 cm3 (DAWN Criteria);

  5. Planned to receive bridging therapy (endovascular therapy after intravenous alteplase) or direct endovascular therapy;

  6. Pre-morbid modified Rankin Scale ≤1;

  7. 6 ≤ NIHSS ≤ 25 before endovascular therapy;

  8. Signed informed consent from subjects or legally authorized representatives

Exclusion Criteria
  1. TMS contraindications include metallic foreign bodies in the head, pacemaker, implantable drug pumps, cochlear implants, etc.
  2. Epilepsy or history of epilepsy, intracranial hypertension, tumor and other serious neurological disorders;
  3. Midline displacement and brain parenchymal mass effect seen in head CT and other images;
  4. Head CT or MRI showed bilateral acute cerebral infarction;
  5. CT or MRI showed a large area of infarction (> 1/3 of the area supplied by middle cerebral artery);
  6. Evidence of acute intracranial hemorrhage;
  7. Before the bridging therapy, other thrombolytic drugs besides alteplase or tenecteplase were used;
  8. A history of congenital or acquired hemorrhagic disease, coagulation factor deficiency, or thrombocytopenia disease;
  9. After blood pressure control, the systolic blood pressure was still ≥180 mmHg or the diastolic blood pressure was ≥110 mmHg;
  10. Known recent or current serum creatinine exceeding 1.5 times the upper limit of normal or estimated glomerular filtration rate (EGFR) < 60 mL/min;
  11. Patients during pregnancy or lactation and within 90 days of planned pregnancy;
  12. Patients with severe mental disorders or dementia who can not cooperate with informed consent and follow-up;
  13. Patients with malignancy or severe systemic disease and expected survival of less than 90 days;
  14. Participants in other clinical intervention studies within 30 days before randomization or who were participating in other clinical intervention studies.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Sham coil stimulationSham stimulationThe sham stimulation coil was used to stimulate the same site, duration and sound as the LF-rTMS group, ensuring no effective stimulation, twice a day for 3 days
LF-rTMSLF-rTMSUsing "8" coil,1-Hz rTMS to stimulate the M1 region of the ipsilateral hemisphere, the stimulation intensity was RMT 100%, 1200pulses/session, two sessions (2400 pulses)/day (interval ≥ 2 hours), lasting 3 days (total 6 sessions, 7200pulses)
Primary Outcome Measures
NameTimeMethod
Rescue penumbra ratio3 days

Baseline penumbra volume - Infarct volume 3 days after randomization / Baseline penumbra volume × 100%

Early neurological improvement (ENI)3 days

The proportion of patients with a reduction of ≥4 on the NIHSS, compared with the baseline score or an NIHSS of 0 or 1

Symptomatic intracranial hemorrhage3 days

The proportion of symptomatic intracranial hemorrhage

Secondary Outcome Measures
NameTimeMethod
Secondary brain injury on imaging90 days

Evaluation of cerebral infarction volume on FLAIR and cerebral atrophy

EQ-5D-5L90 days

The Health Questionnaire (EQ-5D-5L) is a self-report survey that measures quality of life across 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is scored on a 5-level severity ranking that ranges from "no problems" through "extreme problems."

mRS scores of 0-290 days

Proportion of patients with mRS scores of 0-2

Symptomatic intracranial hemorrhage90 days

The incidence of symptomatic intracranial hemorrhage

Barthel index of ADL90 days

Barthel index of ADL, 0-100 (higher score indicates better)

Montreal Cognitive Assessment (MoCA) total score90 days

Total score of the MoCA Performance on the MoCA (0-30; higher score indicates better performance)

Deterioration of neurological function3 days

The incidence of deterioration of neurological function (NIHSS increase ≥4 points)

Adverse events (AE)3 days

Adverse events (AE)

Infarct volume progression3 days

The difference between CT infarct volume and baseline core infarct volume

mRS scores of 0-190 days

Proportion of patients with mRS scores of 0-1

Serious adverse events (SAE)90 days

The proportion of serious adverse events (SAE)

All-cause deaths90 days

The proportion of all-cause deaths

Stroke recurrence90 days

Cerebral infarction, cerebral hemorrhage

Final infarct volume7 and 90 days

Infarct volume on DWI at day 7 after randomization, and infarct volume on FlAIR at Day 90 ± 7 after randomization.

Trial Locations

Locations (1)

Beijing Tian tan Hospital

🇨🇳

Beijing, Beijing, China

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