EnTRIPS
(2026)Objective
Evaluate whether ultra-early remote ischemic postconditioning (RIPC) added to guideline-based therapy improves 90-day functional independence in patients with acute ischemic stroke (AIS) due to large vessel occlusion who underwent endovascular thrombectomy (EVT) with successful recanalization.
Study Summary
• Mortality numerically lower with RIPC (6.8% vs 9.6%; adjusted RR 0.62, 95% CI 0.28–1.36; P=0.23); symptomatic ICH numerically higher (3.8% vs 0.7%; adjusted RR 6.14, 95% CI 0.66–57.38; P=0.11).
• RIPC-related adverse events in 7.5% (mostly minor skin petechiae, arm pain, redness/swelling); no serious device-related events.
• Subgroup signals: benefit in non-LAA stroke (66.7% vs 50.0%; adjusted RR 1.22, P=0.02; interaction P=0.03) and in patients with onset-to-reperfusion time >547 min (65.7% vs 49.3%; adjusted RR 1.34, P=0.04; interaction P=0.03).
Intervention
Remote ischemic postconditioning (RIPC) delivered by a pneumatic device (IPC-906X) as 5 cycles of bilateral upper-arm cuff inflation (5 min at 180 mm Hg) and deflation (3 min) per session (40 min total), initiated within 6 h of EVT and repeated twice daily for 7 days, added to guideline-based AIS therapy.
Inclusion Criteria
Adults with AIS due to large vessel occlusion (A1 ACA, M1/M2 MCA, vertebral, or basilar artery) presenting within 24 h of symptom onset who underwent EVT and achieved successful recanalization (mTICI ≥2b); prestroke mRS ≤1; baseline NIHSS ≥6.
Study Design
Arms: Ultra-early RIPC + guideline-based therapy vs guideline-based therapy alone (open-label, outcome assessor–blinded).
Patients per Arm: 135 RIPC / 135 control (268 in modified intention-to-treat)
Outcome
• Mortality at 90 d: 6.8% vs 9.6%; adjusted RR 0.62 (0.28–1.36), P=0.23.
• Symptomatic ICH: 3.8% vs 0.7%; adjusted RR 6.14 (0.66–57.38), P=0.11.
• RIPC-related AEs: 7.5% (10/133); none in control.
• Interaction favored RIPC in non-LAA stroke (P interaction=0.03) and later reperfusion (P interaction=0.03).
Clinical Question
In adults with acute ischemic stroke from large vessel occlusion who undergo endovascular thrombectomy with successful recanalization, does ultra-early remote ischemic postconditioning (RIPC), initiated within 6 hours after EVT and continued twice daily for 7 days, improve functional independence (mRS 0–2) at 90 days compared with guideline-based therapy alone?
Bottom Line
Ultra-early RIPC after successful EVT was safe but did not significantly improve 90-day functional independence in patients with large vessel occlusion ischemic stroke (60.9% vs 57.8%; adjusted RR 1.07, 95% CI 0.89–1.30; P=0.46).
Major Points
- Multicenter, randomized, controlled, outcome assessor–blinded trial at 8 Chinese hospitals; 270 patients randomized 1:1 to RIPC + guideline therapy vs guideline therapy alone.
- All patients had large vessel occlusion AIS within 24 h of onset and achieved successful EVT recanalization (mTICI ≥2b) before randomization.
- RIPC delivered as 5 cycles of bilateral upper-arm cuff inflation (5 min at 180 mm Hg) and deflation (3 min), twice daily for 7 days, initiated within 6 h of EVT.
- Primary outcome (mRS 0–2 at 90 days) was neutral: 60.9% vs 57.8%; unadjusted RR 1.05 (0.86–1.29), P=0.60; adjusted RR 1.07 (0.89–1.30), P=0.46.
- No significant differences in secondary outcomes (mRS 0, mRS 0–1, Barthel ≥90 at 90 d, NIHSS improvement ≥4 at 7 d/discharge).
- Mortality numerically lower with RIPC (6.8% vs 9.6%; adjusted RR 0.62, 95% CI 0.28–1.36; P=0.23); symptomatic ICH numerically higher (3.8% vs 0.7%; adjusted RR 6.14, 95% CI 0.66–57.38; P=0.11) but neither significant.
- RIPC-related adverse events in 10/133 (7.5%): mostly minor skin petechiae (n=6), arm pain (n=2), redness/swelling (n=2); no serious device-related events.
- Prespecified subgroup interactions: benefit in non-LAA stroke (66.7% vs 50.0%; adjusted RR 1.22, 95% CI 1.05–1.81; P=0.02; interaction P=0.03) and longer onset-to-reperfusion time (>547 min: 65.7% vs 49.3%; adjusted RR 1.34, 1.01–1.77; P=0.04; interaction P=0.03).
- Exploratory biomarker analysis: RIPC group had a smaller decrease in serum GPC-1 (P=0.04) and smaller increase in TNFRSF10A (P=0.047) at 7 days.
- Trial likely underpowered: sample size assumed a 38% relative (≈18% absolute) increase in mRS 0–2, but observed absolute increase was only 3.1%.
Study Design
- Study Type
- Multicenter randomized, controlled, outcome assessor–blinded, open-label trial
- Randomization
- Yes
- Blinding
- Outcome assessor–blinded (open-label for patients and treating clinicians)
- Sample Size
- 270
- Follow-up
- 6 months (primary endpoint at 90 days)
- Centers
- 8
- Countries
- China
Primary Outcome
Definition: Functional independence, defined as modified Rankin Scale score 0–2 at 90 days (modified intention-to-treat)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 57.8% (78/135) | 60.9% (81/133) | Adjusted RR 1.07 (0.89–1.30) | 0.46 |
Limitations & Criticisms
- Open-label design with only outcome assessors blinded; no sham compression used (justified because sham does not induce hemodynamic changes) but risk of performance bias remains.
- Sample size (n=270) likely underpowered — based on assumed 18% absolute increase in mRS 0–2, but observed absolute difference was only 3.1%; CIs did not exclude a clinically meaningful benefit.
- Single-country trial (8 Chinese hospitals) limits external generalizability; race and ethnicity data were not collected.
- Enrollment mixed anterior and posterior circulation strokes, introducing clinical and prognostic heterogeneity.
- Numerical excess of symptomatic intracranial hemorrhage in the RIPC arm (3.8% vs 0.7%) although not statistically significant — warrants monitoring in larger trials.
- Post-randomization dropout and 12.8% protocol non-completion in the RIPC arm (14 patients with incomplete RIPC) may bias effect estimates, although mITT and per-protocol results were consistent.
- Subgroup findings (non-LAA benefit; longer onset-to-reperfusion benefit) are hypothesis-generating and inconsistent with earlier RICAMIS subgroup showing LAA benefit.
Citation
Stroke. 2026; published online June 10, 2026. doi:10.1161/STROKEAHA.126.054857