Background The PerfusiOn imaging Selection of Ischemic sTroke patIents for endoVascular thErapy (POSITIVE) trial was designed to evaluate functional outcome in patients with emergent large vessel occlusion (ELVO) presenting within 0–12 hours with pre-specified bifurcated arms of early and late window presentation, who were selected for endovascular thrombectomy with non-vendor specific commercially available perfusion imaging software. Recent trials demonstrating the benefit of thrombectomy up to 16–24 hours following ELVO removed equipoise to randomize late window ELVO patients and therefore the trial was halted.
Methods Up to 200 patients were to be enrolled in this FDA-cleared, prospective, randomized, multicenter international trial to compare thrombectomy and best medical management in patients with ELVO ineligible for or refractory to treatment with IV tissue plasminogen activator (IV-tPA) selected with perfusion imaging and presenting within 0–12 hours of last seen normal. The primary outcome was 90-day clinical outcome as measured by the raw modified Rankin Scale (mRS) with scores 5 and 6 collapsed (mRS shift analysis).
Results The POSITIVE trial suspended enrollment with the release of results from the DAWN trial and was stopped after the release of the DEFUSE 3 trial results. Thirty-three patients were enrolled (21 for medical management and 12 for thrombectomy). Twelve of the 33 patients were enrolled in the 6–12 hour cohort. Despite the early cessation, the primary outcome demonstrated statistically significant superior clinical outcomes for patients treated with thrombectomy (P=0.0060). The overall proportion of patients achieving an mRS score of 0–2 was 75% in the thrombectomy cohort and 43% in the medical management cohort (OR 4.00, 95% CI 0.84 to 19.2).
Conclusion POSITIVE supports the already established practice of delayed thrombectomy for appropriately selected patients presenting within 0–12 hours selected by perfusion imaging from any vendor. The results of the POSITIVE trial are consistent with other thrombectomy trials. The statistically significant effect on functional improvement, despite the small number of patients, reinforces the robust benefits of thrombectomy.
Clinical trial registration NCT01852201
- CT perfusion
Data availability statement
Data are available upon reasonable request. Data for this study are available upon reasonable request.
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Correction notice This article has been corrected sinec it appeared Online First. Funding statement has updated to "This work was supported by Canon Medical Systems, Medtronic Neurovascular, Penumbra, and Stryker Neurovascular", from "This work was supported by Medtronic".
Contributors All authors made substantial contributions to the study and were involved in the drafting and revising of this manuscript.
Funding This work was supported by Canon Medical Systems, Medtronic Neurovascular, Penumbra, and Stryker Neurovascular.
Competing interests JM is a consultant for Endostream, Viseon, Imperative Care, RIST, Synchron, Viz.ai, Perflow, CVAid, and Cerebrotech, and a shareholder in Rebound, BlinkTBI, Endostream, Viseon, Imperative Care, Serenity, Cardinal Consulting, Q'Apel, NTI, RIST, Synchron, Viz.ai, and Cerebrotech. AHS has two NIH grants as well as financial interest in Adona Medical, Amnis Therapeutics, BlinkTBI, Buffalo Technology Partners, Cardinal Consultants, Cerebrotech Medical Systems, Cognition Medical, Endostream Medical, Imperative Care, International Medical Distribution Partners, Neurovascular Diagnostics, Q’Apel Medical, Radical Catheter Technologies, Rebound Therapeutics Corp, Rist Neurovascular, Sense Diagnostics, Serenity Medical, Silk Road Medical, Spinnaker Medical, StimMed, Synchron, Three Rivers Medical, Vastrax, ICIS, and Viseon; consultant for Amnis Therapeutics, Boston Scientific, Canon Medical Systems USA, Cerebrotech Medical Systems, Cerenovus, Corindus, Endostream Medical, Imperative Care, Integra, Medtronic, MicroVention, Minnetronix Neuro, Northwest University – DSMB Chair for HEAT Trial, Penumbra, Q’Apel Medical, Rapid Medical, Rebound Therapeutics Corp, Serenity Medical, Silk Road Medical, StimMed, Stryker, Three Rivers Medical, VasSol, and W L Gore & Associates; PI or on the Steering Committee for Cerenovus LARGE Trial and ARISE II Trial, Medtronic SWIFT PRIME and SWIFT DIRECT Trials, MicroVention FRED Trial and CONFIDENCE Study, MUSC POSITIVE Trial, Penumbra 3D Separator Trial, COMPASS Trial, and the INVEST Trial. DF has consulting agreements with Medtronic, Cerenovous, Microvention, Stryker, Balt USA, Marblehead, RAPID.AI, and RAPID Medical; research support from Cerenvous, Microvention, Penumbra, Stryker, Balt USA, and Siemens; stock holder in Vascular Simulations, Neurogami, and Marble Head; board member at Vascular Simulations; honorarium at Qapel Medical. MJA is a consultant for Stryker Neurovascular, Penumbra, and Device Proctor for Medtronic. ASA is a consultant for Balt, Johnson and Johnson, Medtronic, Microvention, Penumbra, Scientia, Siemens, Stryker; research support from Balt, Medtronic, Microvention, Penumbra, and Siemens; shareholder in Azimuth, Bendit, Cerebrotech, Endostream, Magneto, Marblehead, Neurogami, Serenity, Synchron, Triad Medical, and Vascular Simulations. BWB is a consultant for Penumbra, Stryker, Medtronic, Cerenovus, Route 92, Artio Medical, 880 Medical, and Rapid Medical; shareholder in Penumbra (stock divested), Route 92, Artio Medical, Rapid Medical, and Marblehead. MTF has grant funding from NIH, Medtronic, Microvention, Stryker, Penumbra, EndoPhys, and Genentech; serves as a consultant for Medtronic, Stryker, Balt USA, VIZ.AI, Genentech, Cerenovus, Corindus, and EndoPhys; consultant for Medtronic, Stryker, MicroVention, Cerenovous, Balt, Phenox, SAB at eLum, Three Rivers Medical, Shape Medical, MiVI; stock holder in RIsT, Inneuro Co, Deinde, eLum, Cerebrotech, Endostream, Three Rivers Medical, BendIT, Blink TBI, Serenity, Scientia. JL has consulting agreements with Penumbra and Stryker. ASP has research grants from Medtronic, Cerenovus, and Stryker; consultant for Microvention, CereVasc, Qpel, Scientica, Arsenal Medical, Merit; stockholder in NTI, Galaxy, and InNeuroCo. ATR has consulting agreements with Stryker Neurovascular, Cerenovus and Microvention. KW is a consultant for Medtronic, Microvention, Penumbra, and Cerenovus. AT is a consultant for Cardinal Consulting, Cerebrotech, Cerenovus, Corindus Robotics, Endostream Medical, Medtronic, Siemens, Imperative Care, Three Rivers Medical, Vastrax, Shape Memory, Serenity Medical, 880 Medical, and Q’Apel; stock holder in Cerebrotech, Endostream Medical, Imperative Care, Three Rivers Medical, Vastrax, Pipe Therapeutics, Q’Apel, Shape Memory, Synchron, Serenity Medical, Blink TBI, Echovate, RIST, Apama, VIZ AI, Early Bird Medicak, Radical Medical, Spinnaker Medical; co-founder of PipeTherapeutics, Neuro Technology Investors (NTI), National Education and Research Center (NEAR), Imperative Care; on the board of BlinkTBI and provides expert testimony for Corindus Vascular Robotics.
Provenance and peer review Not commissioned; externally peer reviewed.