PDF: SERIC
(2025)Objective
Remote ischemic conditioning (unilateral upper limb 200 mm Hg, twice daily for 7 days) vs sham — to evaluate efficacy and safety when added to IV thrombolysis in acute ischemic stroke.
Study Summary
• mRS 0-1: 62.7% RIC vs 56.8% sham; RR 1.10 (95% CI 0.96-1.27); p=0.169 — 5.9% absolute difference, underpowered.
• Hemorrhagic transformation within 24 h similar (6.0% vs 5.6%; RR 1.07; p=0.845) — no safety concern.
• Stroke recurrence at 90 d similar (13.0% vs 12.8%); NIHSS and Barthel index no different.
• Adverse events similar (11.2% vs 8.1%; p=0.221); no serious AEs in either group.
• Largest RIC-with-thrombolysis RCT to date; 5.9% effect smaller than hypothesized 13.1% from phase 2, likely underpowered.
Intervention
Remote ischemic conditioning on unaffected upper limb: 4 cycles of 5 minutes ischemia (cuff 200 mm Hg) alternating with 5 minutes reperfusion, twice daily for 7 consecutive days (14 sessions). Sham arm received identical procedure but with cuff pressure of 60 mm Hg.
Inclusion Criteria
Adults ≥18 with AIS receiving standard alteplase IV thrombolysis within 4.5 hours of onset, pre-thrombolysis NIHSS 4-24, premorbid mRS 0 or 1. Exclusions: severe soft tissue injury, fracture, subclavian steal, peripheral vascular disease, venous thrombosis in upper limbs.
Study Design
Arms: RIC (200 mm Hg) vs Sham RIC (60 mm Hg)
Patients per Arm: RIC 274; Sham 273
Outcome
• mRS 0-2 at 90 days: 78.7% vs 79.5%; RR 0.99 (95% CI 0.91-1.08); p=0.817
• Hemorrhagic transformation within 24 h: 6.0% vs 5.6%; RR 1.07 (95% CI 0.54-2.12); p=0.845
• Stroke recurrence within 90 d: 35/270 (13.0%) vs 34/266 (12.8%); RR 1.01; p=0.950
• AEs within 90 d: 11.2% vs 8.1%; death 4.1% vs 1.9% (p=0.136); no serious AEs in either group
Clinical Question
In patients with acute ischemic stroke who receive IV alteplase thrombolysis, does twice-daily remote ischemic conditioning for 7 days improve the rate of excellent functional outcome (mRS 0-1) at 90 days compared with sham RIC?
Bottom Line
In 547 Chinese patients with AIS receiving IV alteplase, RIC (200 mm Hg, 4 cycles, twice daily × 7 days) did not significantly improve mRS 0-1 at 90 days vs sham (62.7% vs 56.8%; unadjusted RR 1.10, 95% CI 0.96-1.27; p=0.169) but was safe (11.2% AE vs 8.1%; no serious AEs). The 5.9% absolute benefit was smaller than the 13.1% hypothesized from an earlier phase 2 trial, suggesting RIC as an adjunct to thrombolysis does not add meaningful benefit in mild-moderate stroke.
Major Points
- Multicenter participant-blinded blinded-endpoint RCT at 18 hospitals in Jilin province, China, Aug 2021 - May 2023 (Guo/Yang 2025)
- N=558 randomized; 547 in modified ITT (1:1 RIC vs sham) with 95.3% completing follow-up
- Intervention: 200 mm Hg unilateral upper limb cuff, 4×5-min ischemia/reperfusion cycles, twice daily ×7 days (14 sessions)
- Sham: same procedure with 60 mm Hg cuff pressure (insufficient for ischemia)
- Primary endpoint: mRS 0-1 at 90 days (excellent functional outcome)
- Result: 62.7% RIC vs 56.8% sham; RR 1.10 (95% CI 0.96-1.27); p=0.169 — NOT statistically significant
- Absolute difference 5.9% smaller than hypothesized 13.1% (based on phase 2 Meng et al), likely underpowered
- Consistent with RICAMIS treatment effect of 5.4% in non-thrombolysed patients
- Baseline patients had mild strokes (median NIHSS 6, IQR 4-9), limiting ceiling for functional improvement
- Safety excellent: no serious AEs, low rates of local skin changes (1.8%) or arm pain (1.5%)
- Mean time to RIC initiation 13.5 hours after onset (9 h after IVT) — likely beyond neuroprotective window
- Largest RCT of RIC with thrombolysis to date; informs but does not establish RIC role in thrombolysed stroke
Study Design
- Study Type
- Multicenter participant-blinded blinded-endpoint randomized controlled trial (NCT04980625)
- Randomization
- Yes
- Blinding
- Participant-blinded; outcome assessors blinded; implementing nurses unblinded
- Sample Size
- 558
- Follow-up
- 90 days primary; assessments at 24 h, 7 d, 30 d, 90 d
Primary Outcome
Definition: Proportion with mRS 0-1 at 90 days (excellent functional outcome)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 150/264 (56.8%) | 168/268 (62.7%) | - (RR 0.96-1.27) | p=0.169 (unadjusted RR 1.10); adjusted p=0.180 |
Limitations & Criticisms
- Underpowered: sample size calculated assuming 13.1% treatment effect (from phase 2), but observed effect was 5.9% — fewer patients than needed
- Enrolled mild-to-moderate strokes (median NIHSS 6) — limited room for functional improvement and may have diluted RIC benefit
- Mean onset-to-RIC 13.5 h (9 h post-IVT); likely outside optimal neuroprotective window (<6 h) when BBB damage is most modifiable
- Unilateral RIC for 7 days may be lower dose than bilateral RIC ≥10 days used in RICAMIS
- Chinese single-province population; generalizability to other ethnicities unclear
- Nurses performing RIC were unblinded — theoretical risk of expectation bias despite participant/assessor blinding
- Protocol modification during the study may have introduced bias (authors note this limitation)