EnTRIPS
Remote Ischemic Postconditioning in Endovascular Thrombectomy for Stroke: The EnTRIPS Randomized Clinical Trial
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%.
Design
Study Type: Multicenter randomized, controlled, outcome assessor–blinded, open-label trial
Randomization: 1
Blinding: Outcome assessor–blinded (open-label for patients and treating clinicians)
Enrollment Period: April 12, 2021 – March 26, 2025
Follow-up Duration: 6 months (primary endpoint at 90 days)
Centers: 8
Countries: China
Sample Size: 270
Analysis: Modified intention-to-treat (excluded 2 patients who withdrew consent; n=268) with per-protocol sensitivity analysis; treatment effects estimated by modified Poisson regression adjusted for age, prestroke mRS, admission NIHSS, TOAST classification, thrombectomy attempts, and mTICI score
Inclusion Criteria
- Adults with acute ischemic stroke due to large vessel occlusion (A1 segment of anterior cerebral artery, M1/M2 segments of middle cerebral artery, vertebral artery, or basilar artery)
- Presentation within 24 hours of symptom onset
- Underwent endovascular treatment (mechanical thrombectomy, balloon angioplasty, stent placement, or combination)
- Achieved successful recanalization (mTICI score ≥2b)
- Prestroke modified Rankin Scale score ≤1
- Baseline NIHSS score ≥6
- Written informed consent from participant or legally authorized representative
Exclusion Criteria
- Severe soft tissue injuries, fractures, thrombosis, or other peripheral vascular lesions of the upper extremities
- Active visceral hemorrhage
- Acute fundus (ocular) hemorrhage
- Cerebral aneurysm or arteriovenous malformation
- Other conditions unsuitable for bilateral upper-arm compression
Arms
| Field | RIPC + guideline-based therapy | Control |
|---|---|---|
| Intervention | Pneumatic RIPC device (IPC-906X): 5 cycles of bilateral upper-arm cuff inflation (5 min at 180 mm Hg) and deflation (3 min) per session (40 min), twice daily for 7 days, initiated within 6 h of EVT; unilateral if bilateral not feasible; discontinued for significant midline shift or symptomatic ICH | Guideline-based therapy alone (no RIPC or sham compression) |
| Duration | 7 days of RIPC; follow-up to 6 months | 7 days observation; follow-up to 6 months |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Functional independence, defined as modified Rankin Scale score 0–2 at 90 days (modified intention-to-treat) | Primary | 57.8% (78/135) | 60.9% (81/133) | Adjusted RR 1.07 | 0.46 |
| All-cause mortality at 90 days | Secondary | 9.6% (13/135) | 6.8% (9/133) | Adjusted RR 0.62 (95% CI 0.28–1.36) | 0.23 |
| Symptomatic intracranial hemorrhage | Secondary | 0.7% (1/135) | 3.8% (5/133) | Adjusted RR 6.14 (95% CI 0.66–57.38) | 0.11 |
| mRS 0 or 0–1 at 90 days, Barthel Index ≥90 at 90 days, NIHSS improvement ≥4 at 7 days/discharge | Secondary | Reported in Table 2 | Reported in Table 2 | No significant between-group differences (unadjusted or adjusted) | NS |
| Exploratory biomarker – serum GPC-1 change at 7 d | Secondary | Larger decrease | Smaller decrease | — | 0.04 |
| Exploratory biomarker – serum TNFRSF10A change at 7 d | Secondary | Larger increase | Smaller increase | — | 0.047 |
| RIPC-related AEs (any) | Adverse | 7.5% (10/133) RIPC vs 0% (0/135) control | |||
| Arm pain | Adverse | 2/133 (1.5%) RIPC vs 0 control | |||
| Redness or swelling | Adverse | 2/133 (1.5%) RIPC vs 0 control | |||
| Local skin petechiae on arms | Adverse | 6/133 (4.5%) RIPC vs 0 control | |||
| Symptomatic intracranial hemorrhage | Adverse | 3.8% RIPC vs 0.7% control (adjusted RR 6.14, P=0.11) | |||
| Death by 90 days | Adverse | 6.8% RIPC vs 9.6% control (adjusted RR 0.62, P=0.23) | |||
| Serious device-related events | Adverse | None reported | |||
Subgroup Analysis
Heterogeneity of treatment effect detected for stroke cause and time from onset to reperfusion. Non-LAA subgroup: 66.7% vs 50.0% (adjusted RR 1.22, 95% CI 1.05–1.81; P=0.02; interaction P=0.03). Onset-to-reperfusion >547 min (above median): 65.7% vs 49.3% (adjusted RR 1.34, 95% CI 1.01–1.77; P=0.04; interaction P=0.03). No significant interactions for age, sex, prestroke mRS, baseline NIHSS, or mTICI score. Similar signals in per-protocol analysis.
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.
Funding
Investigator-initiated trial (First Affiliated Hospital of Xi'an Jiaotong University); RIPC devices manufactured by Beijing Renqiao Institute of Neuroscience. Full funding disclosures in the published article.
Based on: EnTRIPS (Stroke, 2026)
Authors: Cheng Y, Chen W, Chang M, ..., et al; Luo G (corresponding).
Citation: Stroke. 2026; published online June 10, 2026. doi:10.1161/STROKEAHA.126.054857
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