RAPID SAVE
(2026)Objective
Determine the safety and optimal dose of rapid local ischemic postconditioning (RL-IPostC) delivered via a balloon-guiding catheter immediately after successful mechanical thrombectomy in acute anterior-circulation large-vessel occlusion stroke.
Study Summary
• At 3/3 min × 4, 2 of 5 patients had dose-limiting toxicity from large infarct growth (posterior probability toxicity >15% ≈ 0.95), triggering the predefined stopping rule and eliminating that dose and higher.
• In the 2/2 min group, 14/20 (70%) achieved infarct growth <10 mL at 72 hours, median infarct growth 7.8 mL (IQR 4–25); functional independence (mRS 0–2) at 90 days in 15/20 (75%); no deaths, no symptomatic hemorrhage, no malignant infarction.
Intervention
Rapid local ischemic postconditioning (RL-IPostC) via balloon-guiding catheter at ipsilateral C1–intracranial ICA within 5 minutes of mTICI 2b/3 recanalization, alternating inflation/deflation to interrupt antegrade flow.
Inclusion Criteria
Age ≥18 with acute anterior-circulation ischemic stroke and ICA or M1/M2 occlusion; CTP ischemic core <70 mL, mismatch ratio >1.8, mismatch volume >15 mL; prestroke mRS 0–1 and baseline NIHSS ≥6; femoral puncture within 24 h of onset; thromboembolic etiology; successful thrombectomy reperfusion (mTICI 2b/3) with CTP-to-reperfusion time ≤2 h.
Study Design
Arms: Single-arm adaptive Bayesian (BOIN12) dose-finding trial across 6 prespecified RL-IPostC regimens; no concurrent control.
Patients per Arm: N=25 total (dose 2/2 min × 4: n=20; dose 3/3 min × 4: n=5)
Outcome
• 3/3 min × 4 dose eliminated: toxicity 2/5 (40%), infarct growth <10 mL in 3/5 (60%), median infarct growth 1.7 mL.
• 90-day mRS 0–2: 15/20 (75%) in 2/2 group and 5/5 (100%) in 3/3 group; no deaths, no symptomatic intracerebral hemorrhage, no malignant MCA infarction; hemorrhagic transformation 6/20 vs 1/5 (all asymptomatic).
Clinical Question
In adults with anterior-circulation large-vessel occlusion who achieve mTICI 2b/3 reperfusion, is rapid local ischemic postconditioning (RL-IPostC) delivered by a balloon-guiding catheter safe, and what inflation/deflation regimen provides the best efficacy–toxicity trade-off?
Bottom Line
Rapid local ischemic postconditioning initiated within 5 minutes of successful thrombectomy is feasible; four cycles of 2-minute inflation/2-minute deflation met prespecified safety (toxicity <15%) and efficacy (<10 mL infarct growth at 72 h in ≥60%) thresholds and was selected as the optimal regimen for a future definitive trial, whereas 3/3-minute cycles crossed the toxicity boundary.
Major Points
- Adaptive Bayesian phase I/II BOIN12 design selected 4 cycles of 2 min inflation / 2 min deflation as the optimal RL-IPostC regimen.
- In the 2/2 min group (n=20), 1 dose-limiting toxicity (5%) occurred and 14 patients (70%) had infarct growth <10 mL at 72 h; posterior probability true toxicity >15% was ≈0.16.
- In the 3/3 min group (n=5), 2 dose-limiting toxicities (40%) from large infarct growth (98 mL and 83 mL) triggered the predefined toxicity boundary (posterior probability toxicity >15% ≈0.95), eliminating this dose and all higher levels.
- No malignant MCA infarction, no symptomatic intracerebral hemorrhage, and no deaths were observed in either cohort through 90 days.
- Functional independence (mRS 0–2) at 90 days was reached by 15/20 (75%) in the 2/2 min group and 5/5 (100%) in the 3/3 min group.
- Findings are hypothesis-generating: single-arm, small sample, imaging-based exploratory efficacy; a randomized controlled trial is needed.
Study Design
- Study Type
- Adaptive phase I/II single-arm dose-finding trial (BOIN12 Bayesian Optimal Interval design)
- Randomization
- No
- Blinding
- Open-label intervention; outcome assessors (imaging core lab radiologists and clinical mRS assessors) were blinded to dose
- Sample Size
- 25
- Follow-up
- 90 days (imaging efficacy end point at 72 hours; safety within 7 days)
- Centers
- 6
- Countries
- China
Primary Outcome
Definition: Safety — dose-limiting toxicity within 7 days (malignant MCA infarction, intervention-related complications requiring treatment, or other serious adverse events causally linked to RL-IPostC); toxicity threshold 15%
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| n/a (single-arm dose-finding) | 2/2 min × 4: 1/20 (5%) DLT (infarct growth 154 mL, asymptomatic); 3/3 min × 4: 2/5 (40%) DLTs (infarct growth 98 mL and 83 mL) | - (Posterior probability true toxicity >15%: ≈0.16 (2/2 min) and ≈0.95 (3/3 min)) | n/a |
Limitations & Criticisms
- Single-arm, phase I dose-finding trial with only 25 patients — findings are exploratory and hypothesis-generating.
- Absence of a concurrent control group; median infarct growth cannot serve as a generalizable efficacy end point across cohorts.
- Efficacy end point (infarct growth <10 mL) is imaging-based, not clinical, and used a somewhat arbitrary 10-mL threshold.
- Excluded patients with intracranial atherosclerotic disease and tandem lesions, limiting external validity to a subset of the LVO population.
- Only 2 of the 6 prespecified dose levels were actually explored (dose levels 3 and 4); very low- and high-frequency regimens were untested.
- Six-center trial conducted entirely in China; generalizability to other populations is uncertain.
- No a priori power calculation for functional outcomes; 90-day mRS results are descriptive.
- Dose range was selected empirically because preliminary data were limited.
Citation
Stroke. 2026;57(7). doi:10.1161/STROKEAHA.126.055708 (originally published 11 May 2026)