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| Name | Class |
|---|---|
| Netherlands Organisation for Scientific Research | OTHER_GOV |
| ElectroCore INC | INDUSTRY |
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The main objective of the study will be to investigate whether treatment with non-invasive vagus nerve stimulation (nVNS) on top of best medical practice in acute ischemic stroke patients results in less infarct growth in the penumbra and smaller infarct volumes compared with those of patients not treated with nVNS. The study will be a prospective randomized clinical trial with blinded outcome assessment (PROBE design). 150 patients will be randomized to nVNS with the gammaCore Sapphireâ„¢ device on top of best medical practice versus best medical practice alone (including intravenous thrombolysis and/or thrombectomy if indicated). If patients are randomized to nVNS, two stimulations of two minutes each will be applied in the neck every 15 minutes in the first 3 hours. Thereafter two stimulations will be applied every 8 hours over the next 5 days or until discharge, whichever occurs first. The stimulation side in the neck will be the radiological side of the stroke. The primary endpoint will be the final infarct volume on MRI scan on day 5 of patients treated with nVNS compared with those of patients not treated with VNS.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| non-invasive Vagus Nerve Stimulation | Active Comparator | non-invasive Vagus Nerve Stimulation on top of best medical practice |
|
| Standard Care | No Intervention | Best medical practice alone |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| non-invasive Vagus Nerve Stimulator | Device | Two stimulations of two minutes each will be applied in the neck every 15 minutes in the first 3 hours. Thereafter two stimulations will be applied every 8 hours over the next 5 days or until discharge, whichever occurs first. The stimulation side in the neck will be the radiological side of the stroke. |
| Measure | Description | Time Frame |
|---|---|---|
| Infarct volume | Final infarct volume on MRI scan | On day 5 |
| Measure | Description | Time Frame |
|---|---|---|
| Feasibility of nVNS | Reached if more than 75% of the nVNS treated patients complete treatment for five days or until discharge | On day 5 |
| Tolerability of nVNS | Reached if less than 10% of the patients treated with nVNS has to abort treatment due to side effects |
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Inclusion Criteria:
Exclusion Criteria:
A life expectancy of less than three months
mRS >2 prior to admission
Contra-indication for contrast CT
Contra-indications for VNS:
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| Name | Affiliation | Role |
|---|---|---|
| Marieke JH Wermer, MD PhD | Leiden University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Leiden University Medical Center | Leiden | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33106174 | Derived | van der Meij A, van Walderveen MAA, Kruyt ND, van Zwet EW, Liebler EJ, Ferrari MD, Wermer MJH. NOn-invasive Vagus nerve stimulation in acute Ischemic Stroke (NOVIS): a study protocol for a randomized clinical trial. Trials. 2020 Oct 26;21(1):878. doi: 10.1186/s13063-020-04794-1. |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | May 6, 2025 | May 6, 2025 | SAP_000.pdf |
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| ID | Term |
|---|---|
| D000083242 | Ischemic Stroke |
| D020520 | Brain Infarction |
| D002545 | Brain Ischemia |
| ID | Term |
|---|---|
| D020521 | Stroke |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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PROBE design
|
| On day 5 |
| NIHSS (National Institutes of Health Stroke Scale) on day 5 | The scale runs from 0-42 and quantifies stroke severity | On day 5 |
| Clinical outcome (modified Rankin Scale, mRS) on day 90 | The scale runs from 0-6 and quantifies disabilities: 0 - No symptoms
| On day 90 |
| Occurrence of seizures in the first 90 days | This will be asked to patients and their physician | On day of admission, day 5 and day 90 |
| Occurrence of headache in the first 90 days | A questionnaire will be taken adjusted from van Os et al., neurology 2016 | On day of admission, day 5 and day 90 |
| Occurrence of depression in the first 90 days | HADS (Hospital Anxiety and Depression Scale) questionnaire will be taken. The scale runs from 0-21 and defines the risk of having a depression | On day 90 |
| Quality of life after 90 days | EQ5D-5L questionnaire will be taken. This questionnaire defines a health index based on different questions | On day 90 |
| Cognitive status on day 90 | TICS questionnaire will be taken. This questionnaire can assess cognitive status. | On day 90 |
| Penumbra recovery | Proportion of patients in whom <50% of the penumbra turned into ischemic core on non-contrast CT | On day 3 |
| Blood-brain barrier measurement | Degree of blood-brain barrier leakage on day three measured with CTP | On day 3 |
| D009422 |
| Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D007238 | Infarction |
| D007511 | Ischemia |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009336 | Necrosis |