Evaluation of Transcutaneous Trigeminal Nerve Stimulation for Prevention of Cerebral Vasospasm After Subarachnoid Haemorrhage (TRIVASOSTIM)

Evaluation of the Efficacy of Transcutaneous Trigeminal Nerve Stimulation for Prevention of Cerebral Vasospasm and Its Consequences After Subarachnoid Haemorrhage Due to Ruptured Aneurysm: a Multicentre, Randomized, Double-blind Study

Subarachnoid haemorrhage (SAH) secondary to ruptured aneurysm represents 5 to 15% of all cases of stroke. The mortality rate of SAH is 40% and the risk of serious neurological sequelae among survivors is 10 to 20%.The causes of morbidity and mortality are mainly related to the initial damage induced by SAH and delayed cerebral ischaemia (DCI), which is generally secondary to cerebral vasospasm.

Cerebral vasospasm is one of the main factors of poor prognosis after SAH, as it is associated with a 1.5- to 3-fold increase in the mortality rate during the 2 weeks following SAH in these patients.

Despite a significant improvement in the time to management of this disease and the fact that the ruptured aneurysm is very often rapidly excluded by surgical or endovascular intervention, patients who survive the initial SAH remain at risk of severe complications over the following 2 weeks.

Vascular stenosis of an arterial segment, called cerebral vasospasm, is observed in more than 70 to 95% of cases on digital subtraction angiography between the 7th and 14th days after ruptured aneurysm. This angiographic vasospasm can be responsible for cerebral infarction in 52 to 81% of cases.

Despite 50 years of research, no clearly demonstrated effective treatment for vasospasm is currently available.

This is a multicentre, randomized, comparative study, including 364 patients during the acute phase following ruptured aneurysm, in whom management is very often limited to control of complications, after exclusion of the aneurysm.

The objective of this study is to validate the efficacy of transcutaneous trigeminal nerve stimulation for the prevention of vasospasm and limitation of the consequences of delayed cerebral ischaemia after SAH.

This is an innovative project, as it comprises intervention in these patients prior to the development of complications and could limit the development of these complications. The prevention tool, based on external facial nerve stimulation, is a totally innovative, reversible and noninvasive technique. Use of nerve stimulation in this indication has never been previously reported and could radically modify the intensive care management of this disease over the years to come.

Study Overview

• Status: Completed
• Conditions: Subarachnoid Haemorrhage (SAH)
• Intervention / Treatment: Device: Transcutaneous Electrical Nerve Stimulation (TENS)

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Poitiers, France, 86021
    • BATAILLE

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 years and ≤ 75 years.
• Admission within 48 h after onset of SAH.
• Ruptured cerebral aneurysm confirmed on CT angiography or cerebral angiography.
• Patient classified as grade I-IV according to the WFNS (World Federation of Neurological Surgeons) classification.
• Covered by French national health insurance.
• Absence of active cancer.

Exclusion Criteria:

• Age < 18 years and > 75 years.
• Absence of signature of the informed consent form by the patient or a close relative.
• Person subject to reinforced protection Clinical state on admission classified as WFNS grade V (excessively high mortality rate).
• Intracerebral or intraventricular haemorrhage without subarachnoid involvement.
• Major complication during the aneurysm exclusion procedure.
• SAH with no demonstrated aneurysm.
• Presence of non-ruptured cerebral aneurysm.
• Contraindication to placement of a transcutaneous device.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: active Transcutaneous Electrical Nerve Stimulation; Arm A, treated by active stimulation of the trigeminovascular system after placement of the TENS device.	Device: Transcutaneous Electrical Nerve Stimulation (TENS); All patients will undergo placement of a facial transcutaneous electrical nervous stimulation (TENS) device, but device activation will be randomized [active stimulation vs non-active (placebo) stimulation], for an initial period of 10 days.
Sham Comparator: sham Transcutaneous Electrical Nerve Stimulation; Arm B, treated by non-active (sham) stimulation after placement of the TENS device. This absence of stimulation corresponds to the standard of care currently received by patients hospitalized for SAH due to ruptured aneurysm.	Device: Transcutaneous Electrical Nerve Stimulation (TENS); All patients will undergo placement of a facial transcutaneous electrical nervous stimulation (TENS) device, but device activation will be randomized [active stimulation vs non-active (placebo) stimulation], for an initial period of 10 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Development of cerebral Infarction on MRI (FLAIR sequence)	At 3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Functional disability (modified Rankin scale and GOS).	At 6 months
Evaluation of quality of life (EQ-5D)	At 6 months
An anomaly of perfusion detected on perfusion CT-scan	At day 6
Evaluation of MTT (Mean Transit Time)	At day 6

Collaborators and Investigators

• Sponsor: Poitiers University Hospital
• Investigators: Principal Investigator: Benoit BATAILLE, Poitiers university hospital

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): February 1, 2019
• Study Completion (Actual): May 1, 2019

Study Registration Dates

• First Submitted: June 18, 2015
• First Submitted That Met QC Criteria: June 23, 2015
• First Posted (Estimate): June 26, 2015

Study Record Updates

• Last Update Posted (Actual): November 8, 2019
• Last Update Submitted That Met QC Criteria: November 7, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Subarachnoid Hemorrhage; Vasospasm, Intracranial
• Other Study ID Numbers: TRIVASOSTIM