Implant for Augmentation of Cerebral Blood Flow Trial, Effectiveness and Safety in a 24 Hour Window
- Conditions
- Ischemic Stroke
- Interventions
- Device: Sham Sphenopalatine Ganglion (SPG) StimulationDevice: Active Sphenopalatine Ganglion (SPG) Stimulation
- Registration Number
- NCT00826059
- Lead Sponsor
- BrainsGate
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1078
- Age: Between 40 years and 80 years for male and 85 for female subjects
- Clinical diagnosis of an acute ischemic stroke in the Carotid, Middle or Anterior Cerebral Artery territories
- Imaging findings demonstrating signs of ischemia in the anterior circulation, consistent with the clinical diagnosis
- Baseline NIHSS ≥ 7 and ≤ 18 within 2 hours prior to implantation.
- Ability to initiate treatment within 8- 24 hours from stroke onset
- Signed informed consent from patient him/herself or legally authorized representative if applicable
- Intracranial hemorrhage or hemorrhagic transformation
- Massive stroke
- Acute ischemic stroke in the posterior circulation
- Minor stroke
- Treated with IV-tPA (intravenous tissue Plasminogen Activator) ,IA-tPA (intra-arterial tissue Plasminogen Activator) or neurothrombectomy devices for the current stroke
- Previous stroke in the last 6 months or pre-existing disability
- Patients with bleeding propensity or any condition in the oral cavity that prevents implantation
- Clinical signs and symptoms or imaging evidence of bilateral stroke.
- Treated with IV-tPA ,IA-tPA or neurothrombectomy devices for the current stroke.
- Known cerebral arteriovenous malformation, cerebral aneurysm.
- Clinical suspicion of septic embolus.
- Uncontrolled hypertension (systolic >185 mmHg and/or diastolic >110 mmHg)
- Serious systemic infection.
- Women known to be pregnant or having a positive or indeterminate pregnancy test.
- Patients with other implanted neural stimulator/ electronic devices (pacemakers).
- Life expectancy < 1 year from causes other than stroke.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sham Stimulation Sham Sphenopalatine Ganglion (SPG) Stimulation Sham Implantation and Sham Stimulation during 5 consecutive days \& Standard of Care (SoC). Day 1: First Sham stimulation initiated within 24 hours from stroke onset, following Sham implantation procedure. All subjects will be treated according to SoC for treatment of Acute Ischemic Stroke. Day 2-4: Sham Stimulation sessions repeated daily. Each Sham Stimulation will be initiated within 18-26 hours from the preceding treatment. Day 5: Following completion of the last Sham Stimulation session, imaging performed for lesion assessment. Sham Implant removal will then be performed. Subsequently, patients will be evaluated for safety and effectiveness. Subjects will continue with SoC as needed and discharged from the hospital based on the judgment of the study investigator. Active Stimulation Active Sphenopalatine Ganglion (SPG) Stimulation Implantation/ISS Stimulation during 5 consecutive days \& Standard of Care (SoC). Day 1: First stimulation initiated within 24 hours from stroke onset, following implantation completion. All subjects will be treated according to SoC for treatment of Acute Ischemic Stroke. Day 2-4: ISS Stimulation treatment sessions repeated daily. Each treatment will be initiated within 18-26 hours from the preceding treatment. Day 5: Following completion of the last ISS Stimulation treatment session, imaging performed for assessing Injectable Neuro Stimulator (INS) positioning and/or lesion. Implant removal procedure will then be performed. Subsequently, patients will be evaluated for safety and effectiveness. Subjects will continue with SoC as needed and discharged from the hospital based on the judgment of the study investigator.
- Primary Outcome Measures
Name Time Method Sliding Dichotomy modified Rankin Scale (mRS) at 3 months 90 days±7 days The primary efficacy endpoint is improvement beyond expectations on the modified Rankin Scale at 3 months (sliding dichotomy), assessed in primary populations of:
1. modified intention to treat (mITT)
2. confirmed cortical involvement (CCI), defined as baseline NIHSS ≥ 10 and signs of cortical involvement in baseline imaging (at least one of the following ASPECT regions: M1-M6, Insular Cortex) Type I Error is controlled at an overall level of 0.05 (two-sided) using the Hochberg method.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (73)
Guilford Neurologic Associates
🇺🇸Greensboro, North Carolina, United States
Palmetto Health Richland
🇺🇸Columbia, South Carolina, United States
Erlanger Stroke Center
🇺🇸Chattanooga, Tennessee, United States
Sourasky Medical Center
🇮🇱Tel Aviv, Israel
University Hospital in Krakow
🇵🇱Kraków, Poland
Zugdidi Referral Hospital
🇬🇪Zugdidi, Georgia
The Chaim Sheba Medical Center
🇮🇱Tel HaShomer, Israel
Barzilai Medical Center
🇮🇱Ashkelon, Israel
Rabin Medical Center
🇮🇱Petah tikva, Israel
Policlinico Umberto I
🇮🇹Roma, Italy
Hospital Saint Roch
🇫🇷Nice, France
Unimed Adjara Batumi Referral Hospital
🇬🇪Batumi, Georgia
Hospital de la Cavale Blanche
🇫🇷Brest, France
Department of Medicine, Stroke Program, University of Alberta Hospital
🇨🇦Edmonton, Canada
Helsinki University Hospital
🇫🇮Helsinki, Finland
Aarhus University Hospital
🇩🇰Aarhus, Denmark
Foothills Medical Centre/University of Calgary, Department of Clinical Neurosciences
🇨🇦Calgary, Canada
Intercoastal Medical Group
🇺🇸Sarasota, Florida, United States
Kuopio University Hospital
🇫🇮Kuopio, Finland
Kutaisi Referral Hospital
🇬🇪Kutaisi, Georgia
University of Toledo Medical Center- Campus 1
🇺🇸Toledo, Ohio, United States
Rustavi Central Hospital
🇬🇪Rustavi, Georgia
Emergency Neurology Clinic Neurology Ltd.
🇬🇪Tbilisi, Georgia
High Technology Medical Center University Clinic LTD.
🇬🇪Tbilisi, Georgia
Leipzig University Clinic
🇩🇪Leipzig, Germany
Erlangen University Clinic
🇩🇪Erlangen, Germany
Center for Stroke Research at Charite University of Berlin
🇩🇪Berlin, Germany
Prince of Wales Hospital
🇭🇰Hong Kong, Hong Kong
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong
Konske Hospital
🇵🇱Końskie, Poland
Bialystok University Hospital
🇵🇱Białystok, Poland
Torun Hospital
🇵🇱Toruń, Poland
Clinical Hospital Center Zemun
🇷🇸Zemun, Serbia
Neurologické Oddelenie FN Trnava, Fakultná Nemocnica
🇸🇰Trnava, Slovakia
Sandomierz Hospital
🇵🇱Sandomierz, Poland
Hospital Universitari de Bellvitge
🇪🇸Barcelona, Spain
Institute of Psychiatry and Neurology
🇵🇱Warsaw, Poland
Special Hospital for Cerebrovascular Disease Sveti Sava
🇷🇸Belgrade, Serbia
Hospital Fernando Fonseca
🇵🇹Amadora, Portugal
Centro Hospitalar de Douro e Vouga, EPE - Hospital de São Sebastião
🇵🇹Santa Maria, Portugal
Clinical Centre of Vojvodina
🇷🇸Novi Sad, Serbia
Ramon Y Cajal
🇪🇸Madrid, Spain
Hospital Nord Laennec
🇫🇷Nantes, France
Hospital Pontchaillou
🇫🇷Rennes, France
Hopital Lariboisiere
🇫🇷Paris, France
Central DuPage Hospital
🇺🇸Winfield, Illinois, United States
University of Toledo Medical Center- Campus 2
🇺🇸Toledo, Ohio, United States
Vitkovicka nemocnice a.s. Ostrava Vitkovice
🇨🇿Vítkovice, Czechia
General University Hospital
🇨🇿Prague, Czechia
University Hospital of Ostrava, Ostrava Poruba
🇨🇿Poruba, Czechia
First University Clinic
🇬🇪Tbilisi, Georgia
Altenburg Clinic of Neurology
🇩🇪Altenburg, Germany
Bad Neustadt Neurological Clinic
🇩🇪Bad Neustadt An Der Saale, Germany
Essen University Clinic
🇩🇪Essen, Germany
Hadassah Medical Center
🇮🇱Jerusalem, Israel
Heidelberg University Clinic
🇩🇪Heidelberg, Germany
Technical University Munich
🇩🇪Munich, Germany
Schwarzwald-Baar Clinic
🇩🇪Villingen-Schwenningen, Germany
University Clinic for Neurology
🇲🇰Skopje, North Macedonia
Hospital Sant'Andrea delle Fratte
🇮🇹Perugia, Italy
Unidade de AVC Centro Hospitalar São João
🇵🇹Porto, Portugal
Hospital de Santo Antonio
🇵🇹Porto, Portugal
Hospitalario Universitario de Albacete
🇪🇸Albacete, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Neurologické Oddelenie, Nemocnica s Poliklinikou Spišská
🇸🇰Nová Ves, Slovakia
Hospital de la Santa Creu I Sant Pau
🇪🇸Barcelona, Spain
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Arnau de Vilanova
🇪🇸Lleida, Spain
Hospital Gregorio Maranon
🇪🇸Madrid, Spain
Valladolid - Hospital Clinico
🇪🇸Valladolid, Spain
Complejo Hospitalarion Univiersitario de Santiago
🇪🇸Santiago De Compostela, Spain
Hospital Universitario Son Dureta
🇪🇸Palma De Mallorca, Spain
Lviv National Medical University
🇺🇦Lviv, Ukraine