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

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

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.

Study Overview

• Status: Terminated
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Device: Active Stimulation; Device: Sham Stimulation

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 Type: Interventional
• Enrollment (Actual): 327
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Erlangen, Germany
    • Erlangen University Clinic
  • Essen, Germany
    • Essen University Clinic
  • Heidelberg, Germany
    • Heidelberg University Clinic
  • Leipzig, Germany
    • Leipzig University Clinic
  • Münster, Germany
    • Munster University Clinic
• Spain
  • Barcelona, Spain
    • Hospital Vall d'Hebron
  • Girona, Spain
    • Hospital Universitari de Girona
• United States
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Erlanger Stroke Center

Participation Criteria

Eligibility Criteria

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

Description

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.

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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sliding Dichotomy modified Rankin Scale (mRS) at 3 months	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.	90 ±7 days
Number of participants with Serious Adverse Events	Comparison between the active and sham stimulation groups of all serious adverse events (SAEs)	90 ±7 days
Number of participants with neurological deterioration	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	10 days
Number of participants with implantation complications	The rate of implantation complications as classified by the investigator	90 ±7 days
Number of participants with stimulation-related adverse events	Comparison between the active and sham stimulation groups of stimulation-related adverse events as classified by the investigator	90 ±7 days
Mortality rate	Comparison of mortality rates between the active and sham stimulation groups	90 ±7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sliding Dichotomous 90-day mRS for patients with Aphasia at baseline	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.	90 ±7 days
Binary NIHSS at Day 90	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.	90 ±7 days
Stroke-related quality of life at 3 months: Stroke Impact Scale-16	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	90 ±7 days

Collaborators and Investigators

• Sponsor: BrainsGate

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2009
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: December 5, 2018
• First Submitted That Met QC Criteria: December 5, 2018
• First Posted (Actual): December 6, 2018

Study Record Updates

• Last Update Posted (Actual): January 28, 2019
• Last Update Submitted That Met QC Criteria: January 25, 2019
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: safety; effectiveness; acute ischemic stroke; randomized clinical trial
• 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: CLP1000500-24A

Drug and device information, study documents

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