Clinical trial NCT04014621: Augmenting Cerebral Blood Flow to Preserve the Penumbra Trial
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Ischemic Stroke
Keywords: acute ischemic stroke
randomized clinical trial
anterior circulation
penumbra
Lead sponsor: BrainsGate
Sponsor class: INDUSTRY
First posted: 2019-07-10
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Volume of core expansion
timeFrame: Day 1
Secondary outcomes:
measure: Difference in infarct volume between baseline CTP core volume and follow up NCCT infarct volume.
timeFrame: Day 1
measure: Difference in infarct volume between baseline CTP core volume and Day-5 NCCT infarct volume
timeFrame: Day 5
measure: 3 months mRS
timeFrame: Day 90±7
measure: Increased blood flow in Common Carotid Doppler
timeFrame: Day 2-6
measure: Improvement in hand motor performance
timeFrame: Day 1
Other outcomes:
measure: Safety Data Between the Treatment and Control Arms - Serious Adverse Events
timeFrame: Day 90±7
measure: Safety Data Between the Treatment and Control Arms - Mortality
timeFrame: Day 90±7
measure: Safety Data Between the Treatment and Control Arms - Symptomatic Intracranial hemorrhage (sICH) SAEs
timeFrame: Day 5
measure: Safety Data Between the Treatment and Control Arms - Pain
timeFrame: Day 1 to 5
Locations:
city: Kutaisi
country: Georgia
facility: Academian Z.Tskhakaia West Georgia National Center of Interventional Medicine
city: Rustavi
country: Georgia
facility: Rustavi Central Hospital
city: Tbilisi
country: Georgia
facility: K. Eristavi National center of clinical and experimental surgery's hospital "New Life"
city: Tbilisi
country: Georgia
facility: LTD High Technology Medical Center University Clinic
Study officials:
affiliation: BrainsGate
name: Yoram Slolberg, Dr.
role: STUDY_DIRECTOR
References: