Clinical trial NCT00826059: Implant for Augmentation of Cerebral Blood Flow Trial, Effectiveness and Safety in a 24 Hour Window
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Ischemic Stroke
Keywords: acute ischemic stroke
randomized clinical trial
effectiveness
safety
Lead sponsor: BrainsGate
Sponsor class: INDUSTRY
First posted: 2009-01-21
Enrollment: 1078
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
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 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.

Detailed description: A multi-center, multinational, randomized, blinded, sham control, adjunctive to Standard of Care, parallel arm study and will include ongoing Data Safety and Monitoring Board (DSMB) review of accumulated safety data.

Screening:

Since the treatment should be initiated within 24 hours from stroke onset, the screening window is limited and all procedures should be performed within this window.Subjects with Acute Ischemic Stroke will be screened upon arrival to the hospital. Since the treatment should be initiated between 8 and 24 hours from stroke onset, the screening window is limited and all procedures should be performed as soon as possible. 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 to:

* Group 1: Implantation and ISS Stimulation during five consecutive days \& Standard of Care
* Group 2: Sham Implantation and Sham Stimulation during five consecutive days \& Standard of Care Subjects will be transferred to the implantation procedure facility and the implantation/sham implantation will be performed by a trained physician.

After implantation, active/sham stimulation will be administered in daily 4-hour sessions, beginning immediately following the placement procedure and continuing for 5 consecutive days.

Day 5 / Day of Discharge. Following the last ISS /Sham Stimulation, explantation will be performed and the patients will be evaluated for safety and effectiveness.

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 - 89±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.

Eligibility criteria: Inclusion Criteria:

1. Age: Between 40 years and 80 years for male and 85 for female subjects
2. Clinical diagnosis of an acute ischemic stroke in the Carotid, Middle or Anterior Cerebral Artery territories
3. Imaging findings demonstrating signs of ischemia in the anterior circulation, consistent with the clinical diagnosis
4. Baseline NIHSS ≥ 7 and ≤ 18 within 2 hours prior to implantation.
5. Ability to initiate treatment within 8- 24 hours from stroke onset
6. Signed informed consent from patient him/herself or legally authorized representative if applicable

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 (intravenous tissue Plasminogen Activator) ,IA-tPA (intra-arterial tissue Plasminogen Activator) 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. Clinical signs and symptoms or imaging evidence of bilateral stroke.
9. Treated with IV-tPA ,IA-tPA or neurothrombectomy devices for the current stroke.
10. Known cerebral arteriovenous malformation, cerebral aneurysm.
11. Clinical suspicion of septic embolus.
12. Uncontrolled hypertension (systolic \>185 mmHg and/or diastolic \>110 mmHg)
13. Serious systemic infection.
14. Women known to be pregnant or having a positive or indeterminate pregnancy test.
15. Patients with other implanted neural stimulator/ electronic devices (pacemakers).
16. Life expectancy \< 1 year from causes other than stroke.

Primary outcomes:
measure: Sliding Dichotomy modified Rankin Scale (mRS) at 3 months
timeFrame: 90 days±7 days
Secondary outcomes:
Other outcomes:
measure: Subgroup analysis
timeFrame: 90 days±7 days
measure: Additional clinical efficacy outcome: SIS-16
timeFrame: 90 days±7 days
measure: Additional clinical efficacy outcome: Dichotomy 0-2 mRS at 3 months
timeFrame: 90 days±7 days
measure: Additional clinical efficacy outcome: Dichotomy 0-3 mRS at 3 months
timeFrame: 90 days±7 days
measure: Safety outcome: Serious Adverse Event (SAE)
timeFrame: 90 days±7 days
measure: Safety outcome: Serious Adverse Event (SAE) - Implantation
timeFrame: 90 days±7 days
measure: Safety outcome: Serious Adverse Event (SAE) - Stimulation
timeFrame: 90 days±7 days
measure: Safety outcome: Neurological Deterioration
timeFrame: 10 days
measure: Safety outcome: Mortality
timeFrame: 90 days±7 days
Locations:
city: Sarasota
country: United States
facility: Intercoastal Medical Group
state: Florida
city: Winfield
country: United States
facility: Central DuPage Hospital
state: Illinois
city: Greensboro
country: United States
facility: Guilford Neurologic Associates
state: North Carolina
city: Toledo
country: United States
facility: University of Toledo Medical Center- Campus 1
state: Ohio
city: Toledo
country: United States
facility: University of Toledo Medical Center- Campus 2
state: Ohio
city: Columbia
country: United States
facility: Palmetto Health Richland
state: South Carolina
city: Chattanooga
country: United States
facility: Erlanger Stroke Center
state: Tennessee
city: Calgary
country: Canada
facility: Foothills Medical Centre/University of Calgary, Department of Clinical Neurosciences
city: Edmonton
country: Canada
facility: Department of Medicine, Stroke Program, University of Alberta Hospital
city: Poruba
country: Czechia
facility: University Hospital of Ostrava, Ostrava Poruba
city: Prague
country: Czechia
facility: General University Hospital
city: Vítkovice
country: Czechia
facility: Vitkovicka nemocnice a.s. Ostrava Vitkovice
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Kuopio
country: Finland
facility: Kuopio University Hospital
city: Brest
country: France
facility: Hospital de la Cavale Blanche
city: Nantes
country: France
facility: Hospital Nord Laennec
city: Nice
country: France
facility: Hospital Saint Roch
city: Paris
country: France
facility: Hopital Lariboisiere
city: Rennes
country: France
facility: Hospital Pontchaillou
city: Batumi
country: Georgia
facility: Unimed Adjara Batumi Referral Hospital
city: Kutaisi
country: Georgia
facility: Kutaisi Referral Hospital
city: Rustavi
country: Georgia
facility: Rustavi Central Hospital
city: Tbilisi
country: Georgia
facility: Emergency Neurology Clinic Neurology Ltd.
city: Tbilisi
country: Georgia
facility: First University Clinic
city: Tbilisi
country: Georgia
facility: High Technology Medical Center University Clinic LTD.
city: Zugdidi
country: Georgia
facility: Zugdidi Referral Hospital
city: Altenburg
country: Germany
facility: Altenburg Clinic of Neurology
city: Bad Neustadt An Der Saale
country: Germany
facility: Bad Neustadt Neurological Clinic
city: Berlin
country: Germany
facility: Center for Stroke Research at Charite University of Berlin
city: Erlangen
country: Germany
facility: Erlangen University Clinic
city: Essen
country: Germany
facility: Essen University Clinic
city: Heidelberg
country: Germany
facility: Heidelberg University Clinic
city: Leipzig
country: Germany
facility: Leipzig University Clinic
city: Munich
country: Germany
facility: Technical University Munich
city: Villingen-Schwenningen
country: Germany
facility: Schwarzwald-Baar Clinic
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Petah tikva
country: Israel
facility: Rabin Medical Center
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
city: Tel HaShomer
country: Israel
facility: The Chaim Sheba Medical Center
city: Perugia
country: Italy
facility: Hospital Sant'Andrea delle Fratte
city: Roma
country: Italy
facility: Policlinico Umberto I
city: Skopje
country: North Macedonia
facility: University Clinic for Neurology
city: Białystok
country: Poland
facility: Bialystok University Hospital
city: Końskie
country: Poland
facility: Konske Hospital
city: Kraków
country: Poland
facility: University Hospital in Krakow
city: Sandomierz
country: Poland
facility: Sandomierz Hospital
city: Toruń
country: Poland
facility: Torun Hospital
city: Warsaw
country: Poland
facility: Institute of Psychiatry and Neurology
city: Amadora
country: Portugal
facility: Hospital Fernando Fonseca
city: Porto
country: Portugal
facility: Hospital de Santo Antonio
city: Porto
country: Portugal
facility: Unidade de AVC Centro Hospitalar São João
city: Santa Maria
country: Portugal
facility: Centro Hospitalar de Douro e Vouga, EPE - Hospital de São Sebastião
city: Belgrade
country: Serbia
facility: Special Hospital for Cerebrovascular Disease Sveti Sava
city: Novi Sad
country: Serbia
facility: Clinical Centre of Vojvodina
city: Zemun
country: Serbia
facility: Clinical Hospital Center Zemun
city: Nová Ves
country: Slovakia
facility: Neurologické Oddelenie, Nemocnica s Poliklinikou Spišská
city: Trnava
country: Slovakia
facility: Neurologické Oddelenie FN Trnava, Fakultná Nemocnica
city: Albacete
country: Spain
facility: Hospitalario Universitario de Albacete
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu I Sant Pau
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Lleida
country: Spain
facility: Hospital Arnau de Vilanova
city: Madrid
country: Spain
facility: Hospital Gregorio Maranon
city: Madrid
country: Spain
facility: Ramon Y Cajal
city: Palma De Mallorca
country: Spain
facility: Hospital Universitario Son Dureta
city: Santiago De Compostela
country: Spain
facility: Complejo Hospitalarion Univiersitario de Santiago
city: Valladolid
country: Spain
facility: Valladolid - Hospital Clinico
city: Lviv
country: Ukraine
facility: Lviv National Medical University
Study officials:
affiliation: BrainsGate
name: Eyal Shay
role: STUDY_DIRECTOR
References:
citation: Bornstein NM, Saver JL, Diener HC, Gorelick PB, Shuaib A, Solberg Y, Thackeray L, Savic M, Janelidze T, Zarqua N, Yarnitsky D, Molina CA; ImpACT-24B investigators. An injectable implant to stimulate the sphenopalatine ganglion for treatment of acute ischaemic stroke up to 24 h from onset (ImpACT-24B): an international, randomised, double-blind, sham-controlled, pivotal trial. Lancet. 2019 Jul 20;394(10194):219-229. doi: 10.1016/S0140-6736(19)31192-4. Epub 2019 May 24.