Implant for Augmentation of Cerebral Blood Flow Trial, Effectiveness and Safety in a 24 Hour Window (ImpACT-24A) (ImpACT-24A)

• ClinicalTrials.gov Identifier: NCT03767192
• Recruitment Status: Terminated
• First Posted: December 6, 2018
• Last Update Posted: January 28, 2019
• Sponsor: BrainsGate
• Information provided by (Responsible Party): BrainsGate

Study Description

Brief Summary:

The primary objective of the study is to assess the safety and effectiveness of SPG stimulation with the ISS in patients with an acute ischemic stroke in the anterior circulation initiated within 24 hours from stroke onset.

Condition or disease	Intervention/treatment	Phase
Acute Ischemic Stroke	Device: Active Stimulation; Device: Sham Stimulation	Not Applicable

Detailed Description:

This study was first registered as NCT00826059 on January 19, 2009 under the name ImpACT-24.

Background:

Recruitment to ImpACT-24 was halted, the protocol was amended and then the study was resumed. Later, it was decided to define the first part (before the halt) as a separate study - ImpACT-24A, and identify the continuation of the study as ImpACT-24B. ImpACT-24B continues to be registered as NCT00826059, and ImpACT-24A is registered in this new record.

Detailed Description:

A multi-center, multinational, randomized, double blind, sham control, adjunctive to Standard of Care, parallel arm study with ongoing DSMB review of accumulated safety data.

Screening:

Treatment should be initiated between 8 and 24 hours from stroke onset. All screened patients will be identified by patient number and will sign the informed consent prior to any study procedure initiation.

Period 1: Day 1-5

Day 1- Eligible subjects will be randomized in a 2:1 (ISS Stimulation: Sham Control) ratio:

Group 1: Implantation and ISS Stimulation during five consecutive days & Standard of Care Group 2: Implantation and Sham Stimulation during five consecutive days & Standard of Care The implantation will be performed by a trained physician. Stimulation/sham stimulation will be delivered Day 2-5 ISS / Sham Stimulation will be repeated during the following four consecutive days by trained personnel within 18-26 hours from preceding stimulation.

Day 5 / Day of Discharge. Following the last ISS /Sham Stimulation, explantation will be performed.

Subjects will continue with Standard of Care as needed and will be released from the hospital upon investigator's judgment.

Period 2: Day of Discharge - 90±7 days During this period both groups (ISS Stimulation and Sham Control) will be treated according to Standard of Care either at the hospital, rehabilitation center or at home.

Scheduled visits will be performed on day 30±7 and day 60 ±7, which will include safety and effectiveness assessments.

Final Visit Day 90±7 days: The final visit will be performed at the study site and will include safety and effectiveness evaluations.

Patients will be contacted by study personnel via telephone on Day 180±7 and on Day 360±7 in order to assess their quality of life status.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 327 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double Blind, Sham Control, Parallel Arm Trial to Assess Effectiveness and Safety of the Ischemic Stroke System ISS, as an Adjunct to Standard of Care in Subjects With Acute Ischemic Stroke
• Actual Study Start Date: January 2009
• Actual Primary Completion Date: January 2011
• Actual Study Completion Date: March 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: Active Stimulation; Device: The Ischemic Stroke System SPG stimulation and standard of care	Device: Active Stimulation; SPG stimulation and standard of care
Sham Comparator: Sham Stimulation; Device: Sham control Sham stimulation and standard of care	Device: Sham Stimulation; Sham SPG stimulation and standard of care

Outcome Measures

Primary Outcome Measures :

1. Sliding Dichotomy modified Rankin Scale (mRS) at 3 months [ Time Frame: 90 ±7 days ]

   Final global disability level on the modified Rankin scale (mRS) at 3 months better than expectation (sliding dichotomy analysis) ) assessed in the modified intention to treat (mITT) population defined as all randomized subjects receiving at least the minimal exposure of 1 treatment (ISS Stimulation or Sham Control) session out of the 5 planned sessions.

   mRS Scale:

   • 0 - No symptoms.
   • 1 - No significant disability. Able to carry out all usual activities, despite some symptoms.
   • 2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.
   • 3 - Moderate disability. Requires some help, but able to walk unassisted.
   • 4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.
   • 5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent.
   • 6 - Dead.
2. Number of participants with Serious Adverse Events [ Time Frame: 90 ±7 days ]
   Comparison between the active and sham stimulation groups of all serious adverse events (SAEs)
3. Number of participants with neurological deterioration [ Time Frame: 10 days ]
   Comparison between the active and sham stimulation groups of the rate of neurological deterioration, defined as an increase of 4 or more points on the NIHSS related to any neurological event within the first 10 days after stroke onset
4. Number of participants with implantation complications [ Time Frame: 90 ±7 days ]
   The rate of implantation complications as classified by the investigator
5. Number of participants with stimulation-related adverse events [ Time Frame: 90 ±7 days ]
   Comparison between the active and sham stimulation groups of stimulation-related adverse events as classified by the investigator
6. Mortality rate [ Time Frame: 90 ±7 days ]
   Comparison of mortality rates between the active and sham stimulation groups

Secondary Outcome Measures :

1. Sliding Dichotomous 90-day mRS for patients with Aphasia at baseline [ Time Frame: 90 ±7 days ]

   Sliding Dichotomous 90-day mRS for patients with Aphasia at baseline

   mRS Scale:

   • 0 - No symptoms.
   • 1 - No significant disability. Able to carry out all usual activities, despite some symptoms.
   • 2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.
   • 3 - Moderate disability. Requires some help, but able to walk unassisted.
   • 4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.
   • 5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent.
   • 6 - Dead.
2. Binary NIHSS at Day 90 [ Time Frame: 90 ±7 days ]

   Binary NIHSS (success for score ≤1 or for ≥ 9-point improvement versus baseline)

   The NIHSS (National Institute of Health Stroke Score) is a 42-point scale that quantifies neurological deficits in 11 categories. Ratings for each item are scored with 3 to 5 grades, with 0 as normal.

3. Stroke-related quality of life at 3 months: Stroke Impact Scale-16 [ Time Frame: 90 ±7 days ]

   Stroke-related quality of life at 3 months according to the Stroke Impact Scale-16 (SIS-16)

   The scale is based on a questionnaire with 16 items. Each answer ranges from 1 (poor) to 5 (good). A final single-item Recovery domain assesses the individual's perception of his/her recovery from stroke, where:

   0 = no recovery 100 = full recovery.

   Domain scores range from 0-100 and are calculated using the following equation:

   Domain score = [(Mean item score - 1) / (5-1) ] x 100

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Age: ≥ 18 years and ≤ 85 of both genders.
2. Clinical diagnosis of an acute ischemic stroke in the Carotid, Middle or Anterior Cerebral Artery territories
3. Baseline NIHSS ≥ 7 and ≤ 18
4. Ability to initiate treatment within 8- 24 hours from stroke onset.

Exclusion Criteria:

1. Intracranial hemorrhage or hemorrhagic transformation
2. Massive stroke
3. Acute ischemic stroke in the posterior circulation
4. Minor stroke
5. Treated with IV-tPA ,IA-tPA or neurothrombectomy devices for the current stroke
6. Previous stroke in the last 6 months or pre-existing disability
7. Patients with bleeding propensity or any condition in the oral cavity that prevents implantation
8. Known cerebral arteriovenous malformation, cerebral aneurysm.
9. Clinical suspicion of septic embolus.
10. Uncontrolled hypertension (systolic >185 mmHg and/or diastolic >110 mmHg)
11. Serious systemic infection.
12. Women known to be pregnant or having a positive or indeterminate pregnancy test.
13. Patients with other implanted neural stimulator/ electronic devices (pacemakers).
14. Life expectancy < 1 year from causes other than stroke.

Contacts and Locations

Locations

United States, Tennessee

Erlanger Stroke Center

Chattanooga, Tennessee, United States, 37404

Germany

Erlangen University Clinic

Erlangen, Germany

Essen University Clinic

Essen, Germany

Heidelberg University Clinic

Heidelberg, Germany

Leipzig University Clinic

Leipzig, Germany

Munster University Clinic

Münster, Germany

Spain

Hospital Vall d'Hebron

Barcelona, Spain

Hospital Universitari de Girona

Girona, Spain

Sponsors and Collaborators

BrainsGate

Investigators

• Study Director: Eyal Shay; BrainsGate

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Bornstein NM, Saver JL, Diener HC, Gorelick PB, Shuaib A, Solberg Y, Devlin T, Leung T, Molina CA; ImpACT-24A Investigators. Sphenopalatine Ganglion Stimulation to Augment Cerebral Blood Flow: A Randomized, Sham-Controlled Trial. Stroke. 2019 Aug;50(8):2108-2117. doi: 10.1161/STROKEAHA.118.024582. Epub 2019 May 23.

• Responsible Party: BrainsGate
• ClinicalTrials.gov Identifier: NCT03767192
• Other Study ID Numbers: CLP1000500-24A
• First Posted: December 6, 2018
• Last Update Posted: January 28, 2019
• Last Verified: December 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

Keywords provided by BrainsGate:

acute ischemic stroke; randomized clinical trial; effectiveness; safety

Additional relevant MeSH terms:

Stroke; Ischemic Stroke; Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes