Research Article: Implant for Augmentation of Cerebral Blood Flow Trial-1 (ImpACT-1). A single-arm feasibility study evaluating the safety and potential benefit of the Ischemic Stroke System for treatment of acute ischemic stroke

Date Published: July 3, 2019

Publisher: Public Library of Science

Author(s): Dheeraj Khurana, Subhash Kaul, Dietmar Schneider, Attila Csanyi, Ilona Adam, Nasli R. Ichaporia, Bernd Griewing, Laszlo Csiba, Attila Valikovics, Vinod Puri, Hans Christoph Diener, Stefan Schwab, Andreas Hetzel, Natan Bornstein, Terence J. Quinn.

http://doi.org/10.1371/journal.pone.0217472

Abstract

The Ischemic Stroke System is a novel device designed to deliver stimulation to the sphenopalatine ganglion(SPG).The SPG sends parasympathetic innervations to the anterior cerebral circulation. In rat stroke models, SPG stimulation results in increased cerebral blood flow, reduced infarct volume, protects the blood brain barrier, and improved neurological outcome. We present here the results of a prospective, multinational, single-arm, feasibility study designed to assess the safety, tolerability, and potential benefit of SPG stimulation inpatients with acute ischemic stroke(AIS).

Patients with anterior AIS, baseline NIHSS 7–20 and ability to initiate treatment within 24h from stroke onset, were implanted and treated with the SPG stimulation. Patients were followed up for 90 days. Effect was assessed by comparing the patient outcome to a matched population from the NINDS rt-PA trial placebo patients.

Ninety-eight patients were enrolled (mean age 57years, mean baseline NIHSS 12 and mean treatment time from stroke onset 19h). The observed mortality rate(12.2%), serious adverse events (SAE)incidence(23.5%) and nature of SAE were within the expected range for the population. The modified intention to treat cohort consisted of 84 patients who were compared to matched patients from the NINDS placebo arm. Patients treated with SPG stimulation had an average mRS lower by 0.76 than the historical controls(CMH test p = 0.001).

The implantation procedure and the SPG stimulation, initiated within 24hr from stroke onset, are feasible, safe, and tolerable. The results call for a follow-up randomized trial (funded by BrainsGate; clinicaltrials.gov number, NCT03733236).

Partial Text

In patients with acute ischemic stroke (AIS), reperfusion is associated with better neurological outcomes and anterograde reperfusion is the goal of current therapeutic strategies. Two direct reperfusion therapies have shown benefit in randomized trials and are recommended in guidelines for the management of eligible patients with AIS[1], but both have limitations. Intravenous (IV) thrombolysis use is limited by contraindications to lytic exposure in many patients, increased rates of hemorrhagic transformation compared to untreated patients, and low recanalization rates (30% of visualized artery occlusions)[2]. Endovascular thrombectomy (EVT) is constrained by being limited to large vessel occlusions accessible by thrombectomy devices, availability only at advanced thrombectomy-capable stroke centers, and risks of intracranial hemorrhage and infarcts in new territories[3–4].Therefore, there is a need for a therapy that is safe and efficacious in an extended time window, can be administered in frontline hospitals, does not require advanced imaging for patient selection, and is not associated with hemorrhagic transformation.

A total of 98patients were enrolled in ImpACT-1(Table 2).The mean age was 56.8 year; 52.0%(51/98) had left hemispheric strokes; 34.7%(34/98) were female;76.5%(75/98) were Asian Indians and 23.5% (23/98) were European Caucasians; the mean baseline NIHSS score was 12.2; the mean time from stroke onset(TFSO) was 18.6 hours. Six patients (6.1%) were not treated (Fig 2),five of whom(5.1%) due to device implantation difficulties in agitated patients. In one case (1.0%), the treatment was not initiated due to device malfunction. This small population was comprised of relatively young patients with no significant differences in stroke severity (mean baseline NIHSS 12.0).

This feasibility study evaluated for the first time the use of a novel implantable device (the Ischemic Stroke System) for the treatment of AIS in the anterior circulation upto 24 hours after stroke onset. Results demonstrate safe and tolerable implantation procedure and treatment, and a safety profile comparable with previous studies (12.2%mortality;23.5%SAEs). Despite the known limitations of comparisons with historical controls, this comparison demonstrated a possible signal of potential benefit that warrants further investigation in randomized trials.

ImpACT-1 evaluated a novel device for the treatment of AIS in the anterior circulation upto 24 hours from stroke onset. In this single arm study, we confirmed feasibility of the intervention and did not identify significant safety concern that precludes further study. In comparison to historical controls functional outcomes were better in people treated with the Ischemic Stroke System. This will be formally assessed in the multinational, randomized, double blind, sham controlled pivotal study (IMPACT 24). Source of Funding: The trial was supported by BrainsGate,Ltd.

 

Source:

http://doi.org/10.1371/journal.pone.0217472

 

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