Implant for Augmentation of Cerebral Blood Flow Trial, Effectiveness and Safety in a 24 Hour Window

Ischemic Stroke Clinical Trial

— ImpACT-24B  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00826059
• Other study ID #: CLP1000500
• Status: Completed
• Phase: N/A
• Start date: June 2011
• Est. completion date: June 2018

Study information

• Verified date: March 2019
• Source: BrainsGate
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 1078
• Est. completion date: June 2018
• Est. primary completion date: June 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Ischemia
• Ischemic Stroke
• Stroke

Intervention

Device:
• Active Sphenopalatine Ganglion (SPG) Stimulation
SPG stimulation and standard of care. During all study periods, patients will receive Standard of Care in accordance to the general management of ischemic stroke and secondary prevention, following the guidelines of the American Heart Association/American Stroke Association and of the European Stroke Organization (ESO), including the use of antiplatelets, management of secondary stroke, dyslipidemia, hypertension, diabetes and counseling regarding smoking cessation. Off-label uses of drugs and devices should not occur during any of the study periods.
• Sham Sphenopalatine Ganglion (SPG) Stimulation
Sham SPG stimulation and standard of care. During all study periods, patients will receive Standard of Care in accordance to the general management of ischemic stroke and secondary prevention, following the guidelines of the American Heart Association/American Stroke Association and of the European Stroke Organization (ESO), including the use of antiplatelets, management of secondary stroke, dyslipidemia, hypertension, diabetes and counseling regarding smoking cessation. Off-label uses of drugs and devices should not occur during any of the study periods.

Locations

Country	Name	City	State
Canada	Foothills Medical Centre/University of Calgary, Department of Clinical Neurosciences	Calgary
Canada	Department of Medicine, Stroke Program, University of Alberta Hospital	Edmonton
Czechia	University Hospital of Ostrava, Ostrava Poruba	Poruba
Czechia	General University Hospital	Prague
Czechia	Vitkovicka nemocnice a.s. Ostrava Vitkovice	Vítkovice
Denmark	Aarhus University Hospital	Aarhus
Finland	Helsinki University Hospital	Helsinki
Finland	Kuopio University Hospital	Kuopio
France	Hospital de la Cavale Blanche	Brest
France	Hospital Nord Laennec	Nantes
France	Hospital Saint Roch	Nice
France	Hopital Lariboisiere	Paris
France	Hospital Pontchaillou	Rennes
Georgia	Unimed Adjara Batumi Referral Hospital	Batumi
Georgia	Kutaisi Referral Hospital	Kutaisi
Georgia	Rustavi Central Hospital	Rustavi
Georgia	Emergency Neurology Clinic Neurology Ltd.	Tbilisi
Georgia	First University Clinic	Tbilisi
Georgia	High Technology Medical Center University Clinic LTD.	Tbilisi
Georgia	Zugdidi Referral Hospital	Zugdidi
Germany	Altenburg Clinic of Neurology	Altenburg
Germany	Bad Neustadt Neurological Clinic	Bad Neustadt An Der Saale
Germany	Center for Stroke Research at Charite University of Berlin	Berlin
Germany	Erlangen University Clinic	Erlangen
Germany	Essen University Clinic	Essen
Germany	Heidelberg University Clinic	Heidelberg
Germany	Leipzig University Clinic	Leipzig
Germany	Technical University Munich	Munich
Germany	Schwarzwald-Baar Clinic	Villingen-Schwenningen
Hong Kong	Prince of Wales Hospital	Hong Kong
Hong Kong	Queen Mary Hospital	Hong Kong
Israel	Barzilai Medical Center	Ashkelon
Israel	Hadassah Medical Center	Jerusalem
Israel	Rabin Medical Center	Petah tikva
Israel	Sourasky Medical Center	Tel Aviv
Israel	The Chaim Sheba Medical Center	Tel HaShomer
Italy	Hospital Sant'Andrea delle Fratte	Perugia
Italy	Policlinico Umberto I	Roma
North Macedonia	University Clinic for Neurology	Skopje
Poland	Bialystok University Hospital	Bialystok
Poland	Konske Hospital	Konskie
Poland	University Hospital in Krakow	Kraków
Poland	Sandomierz Hospital	Sandomierz
Poland	Torun Hospital	Torun
Poland	Institute of Psychiatry and Neurology	Warsaw
Portugal	Hospital Fernando Fonseca	Amadora
Portugal	Hospital de Santo Antonio	Porto
Portugal	Unidade de AVC Centro Hospitalar São João	Porto
Portugal	Centro Hospitalar de Douro e Vouga, EPE - Hospital de São Sebastião	Santa Maria
Serbia	Special Hospital for Cerebrovascular Disease Sveti Sava	Belgrade
Serbia	Clinical Centre of Vojvodina	Novi Sad
Serbia	Clinical Hospital Center Zemun	Zemun
Slovakia	Neurologické Oddelenie, Nemocnica s Poliklinikou Spišská	Nová Ves
Slovakia	Neurologické Oddelenie FN Trnava, Fakultná Nemocnica	Trnava
Spain	Hospitalario Universitario de Albacete	Albacete
Spain	Hospital de la Santa Creu I Sant Pau	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitari de Bellvitge	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Arnau de Vilanova	Lleida
Spain	Hospital Gregorio Maranon	Madrid
Spain	Ramon Y Cajal	Madrid
Spain	Hospital Universitario Son Dureta	Palma De Mallorca
Spain	Complejo Hospitalarion Univiersitario de Santiago	Santiago De Compostela
Spain	Valladolid - Hospital Clinico	Valladolid
Ukraine	Lviv National Medical University	Lviv
United States	Erlanger Stroke Center	Chattanooga	Tennessee
United States	Palmetto Health Richland	Columbia	South Carolina
United States	Guilford Neurologic Associates	Greensboro	North Carolina
United States	Intercoastal Medical Group	Sarasota	Florida
United States	University of Toledo Medical Center- Campus 1	Toledo	Ohio
United States	University of Toledo Medical Center- Campus 2	Toledo	Ohio
United States	Central DuPage Hospital	Winfield	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
BrainsGate

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  Denmark,  Finland,  France,  Georgia,  Germany,  Hong Kong,  Israel,  Italy,  North Macedonia,  Poland,  Portugal,  Serbia,  Slovakia,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Subgroup analysis	Primary parameters subgroup analysis by: NIHSS strata, lesion size, time from stroke onset strata, gender, age strata, Diabetes (Y/N), Atrial Fibrillation AFIB (Y/N) and side	90 days±7 days
Other	Additional clinical efficacy outcome: SIS-16	Stroke-related quality of life at 3 months according to the Stroke Impact Scale-16 (SIS-16)	90 days±7 days
Other	Additional clinical efficacy outcome: Dichotomy 0-2 mRS at 3 months	Functional independence at 3 months (modified Rankin Scale 0-2)	90 days±7 days
Other	Additional clinical efficacy outcome: Dichotomy 0-3 mRS at 3 months	Up to moderate disability but ambulatory at 3 months (modified Rankin Scale 0-3)	90 days±7 days
Other	Safety outcome: Serious Adverse Event (SAE)	All Serious Adverse Events (SAEs)	90 days±7 days
Other	Safety outcome: Serious Adverse Event (SAE) - Implantation	SAEs related to implant placement or removal	90 days±7 days
Other	Safety outcome: Serious Adverse Event (SAE) - Stimulation	SAEs related to stimulation	90 days±7 days
Other	Safety outcome: Neurological Deterioration	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
Other	Safety outcome: Mortality	Mortality	90 days±7 days
Primary	Sliding Dichotomy modified Rankin Scale (mRS) at 3 months	The primary efficacy endpoint is improvement beyond expectations on the modified Rankin Scale at 3 months (sliding dichotomy), assessed in primary populations of: modified intention to treat (mITT); 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.	90 days±7 days