POSITIVE Stroke Clinical Trial

Active, not recruiting

Phase N/A Results N/A

Trial Description

Primary Endpoint:
The primary objective is to show that AIS patients, ineligible for or refractory to treatment with IV-tPA, with appropriate image selection, treated with mechanical thrombectomy within 6-12 hours of symptom onset have less stroke related disability and improved good functional outcomes as compared to those treated with best MT with respect to endpoint defined as:
• 90-day global disability assessed via the modified Rankin score (mRS), analyzed using raw mRS scores. Statistical details can be found in section 7.2.
Secondary Endpoints:
- 90-day global disability in the 6-12 hr cohort assessed via the overall distribution of mRS
- Proportion of patients with good functional recovery for the 6-12 hr cohort as defined by mRS 0-2 at 90 days
- Mortality at 30 and 90 days
- Intracranial hemorrhage with neurological deterioration (NIHSS worsening >4) within 24 hours of randomization
- Procedure related serious adverse events (SAE's)
- Arterial revascularization measured by TICI 2b or 3 following device use

Detailed Description

Intravenous (IV) tissue plasminogen activator (tPA) administration has been shown to be safe and effective for treatment of AIS within 3 hours of symptom onset, and newer evidence has shown potential benefit out to 4.5 hours. Mechanical thrombectomy for AIS patients has been shown in clinical trials to be safe up to 8 hours after symptom onset. The rapid progression of thrombectomy devices over the last several years has resulted in faster recanalization times while maintaining a high degree of safety. This has resulted in improved patient outcomes, similar to prior randomized trial data showing improved outcomes over medical therapy or earlier devices. Data from the MERCI trial suggests that patients > 85 as well as those with a baseline NIHSS score > 30 are unlikely to benefit from thrombectomy. Patients with rapidly improving neurologic deficits likely will have an excellent recovery with conventional care, precluding the ability to detect a beneficial treatment effect of thrombectomy.
Pilot data incorporating physiologic imaging has shown that appropriate patients can be selected for thrombectomy. This selection methodology has shown the ability to maintain the same level of safety and efficacy as those patients treated in the highly selective environment of a clinical trial, despite presenting far beyond accepted time based standards. Vertebrobasilar occlusion patients are excluded to maintain a homogenous study population, particularly since no data currently is available addressing the comparability of imaging penumbral patterns in the anterior vs. posterior circulation. This has also been shown to be reproducible at multiple centers and with different imaging modalities. However, all prospective interventional stroke studies performed to date have been restricted by the 8-hour time window.

Conditions

Interventions

  • Endovascular Mechanical Thrombectomy Device
    Other Names: mechanical revascularization
    Intervention Desc: Endovascular intervention can be performed under either general anesthesia or conscious sedation based on best practices as determined by treating physician. Attempt should be made to expedite the transition from imaging to treatment in as rapid a fashion as possible. The subject should be prepared for the planned interventional procedure according to standard hospital procedures. Mechanical revascularization should be performed with the operators standard thrombectomy technique using aspiration or a stent retriever, separately or in combination.
    ARM 1: Kind: Experimental
    Label: Endovascular treatment
    Description: Endovascular intervention can be performed under either general anesthesia or conscious sedation based on best practices as determined by treating physician. Attempt should be made to expedite the transition from imaging to treatment in as rapid a fashion as possible. The subject should be prepared for the planned interventional procedure according to standard hospital procedures. Mechanical revascularization should be performed with the operators standard thrombectomy technique using aspiration or a stent retriever, separately or in combination.

Trial Design

  • Allocation: Randomized
  • Masking: Open Label
  • Purpose: Treatment
  • Endpoint: Safety/Efficacy Study
  • Intervention: Factorial Assignment

Outcomes

Type Measure Time Frame Safety Issue
Primary rates of good functional outcomes compared to best medical therapy (MT) - measured by Modified rankin score (mRS) 90 days No
Secondary • 90-day global disability in the 0-8 hr cohort assessed via the overall distribution of mRS 90 day No
Secondary • Proportion of patients with good functional recovery for the 0-12 hr cohort as defined by mRS 0-2 at 90 days 90 days No
Secondary • Mortality at 30 and 90 days 30 and 90 days Yes
Secondary • Proportion of patients with good functional recovery for the 0-8 hr cohort as defined by mRS 0-2 at 90 days 90 days No
Secondary • ICH with neurological deterioration (NIHSS worsening >4). 90 days Yes
Secondary • Procedure related SAE's 90 days Yes
Secondary • Arterial revascularization measured by TICI 2b or 3 following device use 90 days No
Secondary • 90-day global disability in the 6-12 hr cohort assessed via the overall distribution of mRS 90 day No
Secondary • Proportion of patients with good functional recovery for the 6-12 hr cohort as defined by mRS 0-2 at 90 days 90 days No

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