Low-Frequency REpetitive TRanscranial Magnetic Stimulation Combined With Endovascular Treatment in ACute Ischemic StrokE (RETRACE-II)

Low-Frequency REpetitive TRanscranial Magnetic Stimulation Combined With Endovascular Treatment in ACute Ischemic StrokE (RETRACE-II): A Randomized, Double-Blind, Sham-Controlled, Phase 2 Pilot Trial

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)

Study Overview

• Status: Completed
• Conditions: Stroke, Acute Ischemic
• Intervention / Treatment: Device: LF-rTMS; Device: Sham stimulation

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)

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100070
      • Beijing Tian tan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LF-rTMS; 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)	Device: LF-rTMS; 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);
Sham Comparator: Sham coil stimulation; 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	Device: Sham stimulation; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early neurological improvement (ENI)	The proportion of patients with a reduction of ≥4 on the NIHSS, compared with the baseline score or an NIHSS of 0 or 1	3 days
Symptomatic intracranial hemorrhage	The proportion of symptomatic intracranial hemorrhage	3 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rescue penumbra ratio	Baseline penumbra volume - Infarct volume 3 days after randomization / Baseline penumbra volume × 100%	3 days
Infarct volume progression	The difference between CT infarct volume and baseline core infarct volume	3 days
Final infarct volume	Infarct volume on DWI at day 7 after randomization, and infarct volume on FlAIR at Day 90 ± 7 after randomization.	7 and 90 days
mRS scores of 0-1	Proportion of patients with mRS scores of 0-1	90 days
mRS scores of 0-2	Proportion of patients with mRS scores of 0-2	90 days
Serious adverse events (SAE)	The proportion of serious adverse events (SAE)	90 days
All-cause deaths	The proportion of all-cause deaths	90 days
Symptomatic intracranial hemorrhage	The incidence of symptomatic intracranial hemorrhage	90 days
Deterioration of neurological function	The incidence of deterioration of neurological function (NIHSS increase ≥4 points)	3 days
Stroke recurrence	Cerebral infarction, cerebral hemorrhage	90 days
Adverse events (AE)	Adverse events (AE)	3 days

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Investigators: Principal Investigator: Yongjun MD Wang, MD, Beijing Tiantan Hospital

Publications and helpful links

General Publications

• Ding L, Wang W, Yi T, Zhang G, Han X, Chen W, Wang H, Wang Y, Li Z. Rationale and design of Low-Frequency REpetitive TRanscranial Magnetic Stimulation Combined with Endovascular Treatment in ACute Ischaemic StrokE (RETRACE II): a randomised double-blind controlled multicentre phase II pilot study. Stroke Vasc Neurol. 2025 Oct 28:svn-2025-004331. doi: 10.1136/svn-2025-004331. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2024
• Primary Completion (Actual): April 15, 2025
• Study Completion (Actual): July 2, 2025

Study Registration Dates

• First Submitted: August 24, 2023
• First Submitted That Met QC Criteria: September 26, 2023
• First Posted (Actual): October 3, 2023

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 3, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Acute ischemic stroke; Endovascular therapy; LF-rTMS; Phase 2 Pilot Trial
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Ischemic Stroke
• Other Study ID Numbers: HX-A-2023002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No