Transcranial Direct Current Stimulation in Acute Ischemic Stroke Treatment

The presence of SICH will be assessed on 24-hour post-stimulation non-contrast CT scan. SICH will be defined as an intracranial hemorrhage with an increase of ≥ 4 points on the National Institute of Health Stroke Scale (NIHSS) within 24h after stimulation. In case of sudden worsening of neurostatus anytime within first 24 hours after stimulation, first follow-up CT will be performed immediately (earlier). The treatment will be considered to have exhibited adequate safety if tDCS results in lower or equivalent rates of SICH compared to sham.

The AICH will be defined as an intracranial hemorrhage on 24h post-stimulation non-contrast CT scan that is not associated with NIHSS worsening ≥ 4 within 24 hours after stimulation.The treatment will be considered to have exhibited adequate safety if tDCS results in lower or equivalent rates of AICH compared to sham.

Early neurological deterioration will be defined as worsening ≥ 4 on NIHSS during the 24-hour period after stimulation without intracranial hemorrhage. The treatment will be considered to have exhibited adequate safety if tDCS results in lower or equivalent rates of early neurological deterioration compared to sham.

Mortality will be defined as death or modified Rankin Scale of 6. The treatment will be considered to have exhibited adequate safety if tDCS results in lower or equivalent rates of mortality compared to sham.

A serious adverse event is any adverse event that is fatal, is lifethreatening, is permanently or substantially disabling, requires or prolongs hospitalization, or requires medical or surgical intervention to prevent one of the above outcomes. The rate of serious adverse events will be compared between the active treatment and sham patients, and between higher and lower dose tiers.The treatment will be considered to have exhibited adequate safety if tDCS results in lower or equivalent rates of serious adverse events compared to sham.

The percentage of the patients completing the protocol-assigned stimulation treatment. A patient will be considered to have tolerated the stimulation if at least 75 percent of the stimulation period is completed. The treatment will be considered generally tolerable if, among all enrolled patients, tolerated procedures are achieved in ≥90 percent of patients without early cessation.

The rate and severity of cutaneous, neurologic, nociceptive or other adverse effects will be assessed. At the end of each 20-minute stimulation cycle, a tolerability form will be completed based on validated cutaneous, neurological and pain items of the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTAE). A separate tolerability form will be completed by the patient at the of each stimulation cycle.

The speed with which tDCS will be implemented. The predefined success threshold for feasibility will be median time from randomization to tDCS initiation ≤ 10 minutes in the last 10 enrolled patients.

By comparing the baseline CTP imaging with the CT imaging at 24-hour post-stimulation the final infarct growth will be calculated as: final infarct volume at 24h follow-up CT minus ischemic core volume at baseline CTP. This imaging efficacy endpoint will be characterized in the active and sham patients, and in higher and lower dose tiers. The study is underpowered to definitely assess reduction of final infarct growth, however, the treatment may be considered to be effective if tDCS results in higher reduction of final infarct growth compared to sham.

At 24-hour post stimulation, a severity of early neurological deficit will be assessed using the National Institutes of Health Stroke Scale (NIHSS). At day 90 post-stimulation, residual NIHSS will be assessed. These clinical efficacy endpoints will be characterized in the active and sham patients, and in higher and lower dose tiers. The study is underpowered to definitely assess efficacy, however, the treatment may be considered to be efficacious if tDCS results in an improved neurological deficit compared to sham.

At day 90 post-stimulation, a rate of global disability will be assessed using the modified Rankin Scale (mRS). This clinical efficacy endpoint will be characterized in the active and sham patients, and in higher and lower dose tiers. The study is underpowered to definitely assess efficacy, however, the treatment may be considered to be efficacious if tDCS results in lower global disability compared to sham.

At day 90 post-stimulation, a measure of global disability will be assessed using the Barthel Index (BI). This clinical efficacy endpoint will be characterized in the active and sham patients, and in higher and lower dose tiers. The study is underpowered to definitely assess efficacy, however, the treatment may be considered to be efficacious if tDCS results in improved instrumental activities of daily living compared to sham.

At day 90 post-stimulation, a health-related quality of life will be assessed using the EuroQol- 5 Dimension instrument (EQ-5D). This clinical efficacy endpoint will be characterized in the active and sham patients, and in higher and lower dose tiers. The study is underpowered to definitely assess efficacy, however, the treatment may be considered to be efficacious if tDCS results in an improved health-related quality of life compared to sham.

At day 90 post-stimulation, a granular degree of disability will be assessed using the Academic Medical Center (AMC) Linear Disability Score. This clinical efficacy endpoint will be characterized in the active and sham patients, and in higher and lower dose tiers. The study is underpowered to definitely assess efficacy, however, the treatment may be considered to be efficacious if tDCS results in an improved granular degree of disability compared to sham.