Augmenting Cerebral Blood Flow to Preserve the Penumbra Trial (ImpACT-P)

A Multicenter, Randomized, Double Blind, Sham Controlled Trial to Assess the Efficacy of the Ischemic Stroke System (ISS) in Preventing Progressive Reduction of Salvageable Brain Tissue Volume in Subjects With Acute Ischemic Stroke

The primary objective of the study is to demonstrate that SPG (Sphenopalatine Ganglion) stimulation started within 6 hours from stroke onset slows the expansion of the infarct core volume in acute ischemic stroke.

Study Overview

• Status: Unknown
• Conditions: Ischemic Stroke
• Intervention / Treatment: Device: SPG stimulation

Detailed Description

The goal of this study is to identify Acute Ischemic Stroke patients who have a potentially salvageable penumbra and to test if 6 hours of SPG (Sphenopalatine Ganglion) stimulation may "freeze" the volume of the penumbra and reduce the extent of tissue death.

Following a minimally-invasive implantation of the ISS injectable implant, patients will be randomized to either the Treated or Control arm in a 1:1 ratio. Randomization will be dynamic according to the patient's baseline covariates of core volume, total volume, Hypoperfusion Intensity Ratio (HIR), time to baseline imaging, age, NIHSS. Patients in the Treated arm will be treated with active SPG stimulation while patients in the Control arm will undergo sham treatment. After treatment/sham treatment, patients in both groups will undergo a follow up brain non-contrast CT, CT perfusion and CT angiography imaging, 6:45hrs±15min after baseline CTP initiation.

In the case the patient is cooperative, hand strength (pinch and grasp) evaluations should be assessed before and during the 1st treatment/ sham SPG stimulation session.

Following the assessment of the penumbra (after 6 hours) patients will be treated or sham treated for 5 additional consecutive sessions (4 hours each), the first starting within 18-24 hours from stroke onset and the others 18-26 hours from previous treatment initiation and will be followed for 90 days to assess their clinical outcome. In one session (preferably at day 2) Common Carotid Doppler examination is performed to evaluate blood flow dynamics before and during the treatment/sham session.

After the last treatment session, the implant is removed.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Michael Segev; Phone Number: 115 +972 4 637 7774; Email: michaels@brainsgate.com
• Study Contact Backup: Name: Noam Levy; Phone Number: 103 +972 4 637 7774; Email: noaml@brainsgate.com

Study Locations

• Georgia
  • Kutaisi, Georgia
    • Recruiting
    • Academian Z.Tskhakaia West Georgia National Center of Interventional Medicine
    • Contact: Tamar Janelidze, Dr.
  • Rustavi, Georgia
    • Not yet recruiting
    • Rustavi Central Hospital
    • Contact: Nino Kharaishvili, Dr.
  • Tbilisi, Georgia
    • Recruiting
    • K. Eristavi National center of clinical and experimental surgery's hospital "New Life"
    • Contact: Natia Zarkua, Dr.
  • Tbilisi, Georgia
    • Not yet recruiting
    • LTD High Technology Medical Center University Clinic
    • Contact: Giorgi Ingorokva, Prof.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 88 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signs & symptoms consistent with the diagnosis of large vessel occlusion in the anterior circulation
2. Age 18-90 years
3. Baseline NIHSS ≥ 10
4. Ability to initiate treatment within 6 hours from stroke onset. Stroke onset is defined as the time the patient was last seen well.
5. Large vessel total occlusion by CTA
6. Penumbra ≥ 50ml (Difference between Tmax6 volume and the ischemic core volume (CBF<38% volume)
7. Mismatch (Tmax6 volume/ischemic core volume (CBF<38% volume) ≥1.5
8. Core and HIR (Tmax10 / Tmax6) volumes: 1. HIR ≥ 0.5 or 2. 0.35 ≤ HIR < 0.5 and "core volume/time from onset to imaging" ≥ 7mililiter/hour
9. Signed informed consent from patient him/herself or legally authorized representative.

Exclusion Criteria:

1. Unable to undergo a contrast brain perfusion scan, including an allergy to contrast media
2. Opportunity for reperfusion therapy (IV thrombolysis or endovascular treatment)
3. Neuro-imaging evidence of any intracranial hemorrhage or hemorrhagic transformation of brain infarct or other significant abnormality (e.g. tumor, abscess, suspect for subarachnoid hemorrhage, arteriovenous malformation, cerebral aneurysm).
4. Significant mass effect with midline shift.
5. Infarct core volume >150 milliliter
6. Old non-lacunar infarct in the anterior circulation on the ipsilateral hemisphere.
7. Previous stroke in the last 6 months or previous stroke with existing sequelae or with mRS > 0 for any reason
8. Pre-existing Modified Rankin Score >1, even if not stroke-related.
9. Acute symptomatic arterial occlusions in more than one vascular territory confirmed on CTA/MRA (e.g., bilateral MCA occlusions, or an MCA and a basilar artery occlusion).
10. Seizures at stroke onset
11. Baseline blood glucose of <50mg/dL (2.78 mmol) or >400mg/dL (22.20 mmol)
12. Severe, sustained hypertension (Systolic BP >185 mmHg or Diastolic BP >110 mmHg)
13. Current participation in another investigational drug or device study
14. Presumed septic embolus; suspicion of bacterial endocarditis
15. Clinical signs and symptoms or evidence for a relevant lesion by neuro-imaging of an acute ischemic stroke in the posterior circulation (Vertebral, Basilar and/or Posterior Cerebral Artery territories), including but not limited to brain-stem findings and/or cerebellar findings and/or isolated homonymous hemianopia or cortical blindness.
16. Patients with bleeding propensity and/or one of the following: INR > 1.8, prolonged activated partial thromboplastin time (aPTT) ≥ 45 sec., platelets count < 75×10^9/L.
17. Serious systemic infection.
18. Women known to be pregnant or having a positive or indeterminate pregnancy test.
19. Patients with other implanted neural stimulator/ electronic devices (pacemakers).
20. History of SPG ablation ipsilateral to the stroke side.
21. Any condition in the oral cavity that prevents implantation of the INS.
22. Known sensitivity to any medications to be used during study.
23. Subjects who have a clinically significant or unstable medical or surgical condition that may preclude safe and complete study participation. Conditions may include: cardiovascular, vascular, pulmonary, hepatic, renal or neurological (other than acute ischemic stroke), or neoplastic diseases, as determined by medical history, physical examination, laboratory tests, or ECG.
24. Subjects who, in the judgment of the investigator, are likely to be non-compliant or uncooperative during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treated; Treated arm patients will be implanted and treated with one session of SPG stimulation for 6 hours and 5 additional consecutive sessions (4 hours each) of SPG stimulation, the first starting within 18-24 hours from stroke onset and the others 18-26 hours from previous treatment initiation.	Device: SPG stimulation; The BrainsGate Ischemic Stroke System (ISS) consists of an implantable neurostimulator designed to deliver electrical stimulation to the sphenopalatine ganglion (SPG) and/or nerves within the greater palatine canal and pterygopalatine fossa.
Sham Comparator: Control; Control arm patients will be implanted and receive 6 hours of sham stimulation and 5 additional consecutive sessions (4 hours each) of sham stimulation, the first starting within 18-24 hours from stroke onset and the others 18-26 hours from previous treatment initiation.	Device: SPG stimulation; The BrainsGate Ischemic Stroke System (ISS) consists of an implantable neurostimulator designed to deliver electrical stimulation to the sphenopalatine ganglion (SPG) and/or nerves within the greater palatine canal and pterygopalatine fossa.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Volume of core expansion	The primary outcome measure is the volume of core expansion (in milliliters) in 6:45h±15 min. Core expansion is the difference of two volumes: Core volume (CBF<38%) in follow up CTP (at 6:45h±15 min) and Core volume (CBF<38%) in baseline CTP. The difference in the mean core expansion between the Treated and Control groups will be assessed as a continuous variable with adjustment for baseline covariates (Core volume, Total volume, HIR, Time to baseline imaging). The two-sided significance level is 0.05. Handling of missing data in the primary analysis: Patients who die before the 6:45h±15 min follow-up imaging will be assigned a final core volume that equal the baseline total volume. Patients with non-interpretable follow-up imaging will be excluded from the analysis.	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in infarct volume between baseline CTP core volume and follow up NCCT infarct volume.	Difference in infarct volume (in milliliters) between baseline CTP core volume (CBF<38%) and follow up 6:45h±15 min NCCT infarct volume, adjusted using stratification parameters (Core volume, Total volume, HIR, Time to baseline imaging).	Day 1
Difference in infarct volume between baseline CTP core volume and Day-5 NCCT infarct volume	Difference in infarct volume (in milliliters) between baseline CTP core volume (CBF<38%) and Day-5 NCCT infarct volume, adjusted using stratification parameters (Core volume, Total volume, HIR, Time to baseline imaging).	Day 5
3 months mRS	mRS at 90-day: Utility weighted mRS; mRS Dichotomy 0-2; mRS Dichotomy 0-3	Day 90±7
Increased blood flow in Common Carotid Doppler	Increased blood flow in Common Carotid Doppler (if available).	Day 2-6
Improvement in hand motor performance	Improvement in hand motor performance (if available) using a hand dynamometer (Baseline Hydraulic Hand Dynamometers, Fabrication Enterprises Inc, White Plains NY, USA).	Day 1

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Data Between the Treatment and Control Arms - Serious Adverse Events	Incidence of Serious Adverse Events	Day 90±7
Safety Data Between the Treatment and Control Arms - Mortality	Incidence of Mortality	Day 90±7
Safety Data Between the Treatment and Control Arms - Symptomatic Intracranial hemorrhage (sICH) SAEs	Incidence of symptomatic intracranial hemorrhage (sICH) SAEs	Day 5
Safety Data Between the Treatment and Control Arms - Pain	Incidence of Pain adverse events during stimulation	Day 1 to 5

Collaborators and Investigators

• Sponsor: BrainsGate
• Investigators: Study Director: Yoram Slolberg, Dr., BrainsGate

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2019
• Primary Completion (Anticipated): January 1, 2021
• Study Completion (Anticipated): April 1, 2021

Study Registration Dates

• First Submitted: October 28, 2018
• First Submitted That Met QC Criteria: July 9, 2019
• First Posted (Actual): July 10, 2019

Study Record Updates

• Last Update Posted (Actual): October 30, 2019
• Last Update Submitted That Met QC Criteria: October 29, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: acute ischemic stroke; randomized clinical trial; anterior circulation; penumbra
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Ischemia
• Other Study ID Numbers: CLP0050615

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No