Objective:To determine the effect of remote ischemic post-conditioning (RIPC) on acute ischemic stroke (AIS) patients undergoing intravenous thrombolysis (IVT).Methods:A single-center, randomized controlled trial was performed with AIS patients receiving IVT. Patients in the RIPC group were administered RIPC treatment (after IVT) during hospitalization. The primary endpoint was a score of 0 or 1 on the modified Rankin scale (mRS) at day 90. The safety, tolerability and neuroprotection biomarkers associated with RIPC were also examined.Results:We collected data from both RIPC (n=34) and controls (n=34). The average duration of hospitalization was 11.2 days. There was no significant difference between the two groups at admission for the NIHSS score (p=0.364) or occur to treatment time (p=0.889). An excellent recovery (mRS 0–1) at 3 months was obtained in 71.9% of the patients in the RIPC group vs 50.0% in the control group (adjusted risk ratio, 9.85; 95% CI, 1.54 to 63.16; P = 0.016). We further found significantly lower plasma S100 β (p=0.007) and higher vascular endothelial growth factor (p = 0.003) levels in the RIPC group than in controls.Conclusions:Repeated RIPC combined with IVT can significantly facilitate recovery of nerve function and improve clinical prognosis of patients with AIS.ClinicalTrial.gov identifier:NCT03218293Classification of Evidence:This study provides Class IV evidence that RIPC following tPA treatment of AIS significantly increases the proportion of patients with MRS 0 or 1 at 90 days.

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