RIC-VS: Remote Ischemic Preconditioning in Vestibular Schwannoma Surgery

Sponsor

University Hospital Tuebingen (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05567341

Collaborator

(none)

120

Enrollment

Location

Arms

Anticipated Duration (Months)

4.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Vestibular schwannomas are primarily benign (WHO grade I) tumors originating from the Schwann cells of the vestibular nerve and are among the most common tumors of the skull base. Common treatment options are surgical tumor resection or targeted radiation therapy. The special challenge of surgical treatment is the functional preservation of the cranial nerves, especially the cochlear and facial nerves. Perioperative ischemia of the cochlea and cochlear nerve is postulated as the underlying mechanism of postoperative hearing loss. Ischemic preconditioning is a non-invasive procedure that triggers the release of vasoactive cytokines and mediators by repeated short-term induction of limb ischemia. Improved perfusion of critically perfused end organs as well as a reduction of cerebral infarct volumes has already been shown in other pathologies. In the planned study, possible neuroprotective effects of remote ischemic preconditioning on postoperative hearing as well as facial nerve function in patients with vestibular schwannomas will be examined.

Condition or Disease	Intervention/Treatment	Phase
Vestibular Schwannoma	Procedure: Remote ischemic preconditioning Procedure: Sham-control	N/A

Detailed Description

Purpose: Does remote ischemic preconditioning improve hearing and/or facial nerve palsy after resection of vestibular schwannomas?

Study Design: Prospective, randomized, double-blind, single-center.

Case number: The study should include 120 patients (60 treatment arm, 60 control arm). Case number calculation (mean effect sizes, chi-square test, alpha error = 0.05, beta error = 20%) results in a necessary total patient number of 100 with 50 patients per group. Including the expected dropout rate (approx. 20%), the required total number of study participants is set at 120 patients. With approximately 55 patients/year in whom anatomic preservation of the cochlear nerve is possible intraoperatively, the total study duration is estimated to be approximately 2-2.5 years.

Study procedure: Day 1

Preoperative pure tone audiometry including speech discrimination and preoperative AEP measurement
preoperative assessment of facial nerve function according to House and Brackmann and photo documentation
Preoperative blood sample (Hg, WBC, platelet count, creatinine, sodium, potassium, CRP, PCT, IL-6, INR, Quick, aPTT, d-dimer)
Evaluation of inclusion and exclusion criteria, informed consent

Day 2

Randomization
At skin incision RIC procedure or sham control.
RIC arm: 5 minutes inflation of a blood pressure cuff to 200mmHg on the right arm, then 5 minutes rest, the procedure will be performed 4 times in total.
Control arm: 5 minutes inflation of a blood pressure cuff to 0mmHg on the right arm, then 5 minutes rest, the procedure will be performed 4 times in total.
Performance of tumor resection under electrophysiological monitoring.
blood sample (Hg, WBC, platelet count, creatinine, sodium, potassium, CRP, PCT, IL-6, INR, Quick, aPTT, d-dimer)

Day 3

blood sample (Hg, WBC, platelet count, creatinine, sodium, potassium, CRP, PCT, IL-6, INR, Quick, aPTT, d-dimer)
Clinical assessment of facial nerve function
Evaluation of complications

Before discharge

Clinical assessment of facial nerve function and photo documentation
Evaluation of complications occurring in the course of the procedure
Postoperative AEP measurement and pure tone audiometry incl. speech discrimination

Outpatient follow-up after 3 months

Evaluation of postoperative pure tone audiometry incl. speech discrimination
Clinical assessment of facial nerve function and photo documentation

Objective:

Primary outcome: patients undergoing RIC will show better hearing 3 months postoperatively than the sham control group.

Secondary outcome hypothesis: patients undergoing RIC will show better postoperative facial nerve function than the sham control group before discharge and 3 months postoperatively.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

group 1: intervention, remote ischemic preconditioning for 4x5 minutes at the beginning of the surgery group 2: sham-control (4x5 min without compression of the extremity)group 1: intervention, remote ischemic preconditioning for 4x5 minutes at the beginning of the surgery group 2: sham-control (4x5 min without compression of the extremity)

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

only the study nurse who performs the intervention is aware of the study arm

Primary Purpose:

Prevention

Official Title:

Remote Ischemic Preconditioning in Vestibular Schwannoma Surgery and Its Neuroprotective Effect on the Cochlear and Facial Nerve Function

Anticipated Study Start Date :

Oct 1, 2022

Anticipated Primary Completion Date :

Jan 1, 2025

Anticipated Study Completion Date :

Jan 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RIC On the right upper extremity a blood pressure cuff is inflated to 200mmHg for 4x5min at the beginning of the surgery	Procedure: Remote ischemic preconditioning A blood pressure cuff is inflated to 200 mmHg for 4x5 min (5 min rest between cycles) at the right upper extremity when the vestibular schwannoma surgery is started
Sham Comparator: Control On the right upper extremity a blood pressure cuff is inflated to 0mmHg for 4x5min at the beginning of the surgery	Procedure: Sham-control A blood pressure cuff is inflated to 0 mmHg for 4x5 min (5 min rest between cycles) at the right upper extremity when the vestibular schwannoma surgery is started

Arm

Intervention/Treatment

Experimental: RIC

On the right upper extremity a blood pressure cuff is inflated to 200mmHg for 4x5min at the beginning of the surgery

Procedure: Remote ischemic preconditioning

A blood pressure cuff is inflated to 200 mmHg for 4x5 min (5 min rest between cycles) at the right upper extremity when the vestibular schwannoma surgery is started

Sham Comparator: Control

On the right upper extremity a blood pressure cuff is inflated to 0mmHg for 4x5min at the beginning of the surgery

Procedure: Sham-control

A blood pressure cuff is inflated to 0 mmHg for 4x5 min (5 min rest between cycles) at the right upper extremity when the vestibular schwannoma surgery is started

Outcome Measures

Primary Outcome Measures

postoperative hearing [3 months (± 6 weeks) after surgery]
hearing on pure tone audiometry according to AAO-HNS/Gardner-Robertson

Secondary Outcome Measures

postoperative facial nerve function [up to 8 days after surgery]
facial nerve function according to House and Brackmann
postoperative facial nerve function [3 months (± 6 weeks) after surgery]
facial nerve function according to House and Brackmann

Other Outcome Measures

postoperative hearing [up to 8 days after surgery]
hearing on pure tone audiometry according to AAO-HNS/Gardner-Robertson
laboratory findings [within 4 hours after surgery]
White blood count
laboratory findings [within 4 hours after surgery]
C-reactive protein
laboratory findings [within 4 hours after surgery]
Procalcitonin
laboratory findings [within 4 hours after surgery]
Interleukin 6
laboratory findings [within 4 hours after surgery]
D-Dimer
laboratory findings [within 4 hours after surgery]
platelet count
laboratory findings [within 4 hours after surgery]
International normalized ratio (INR)
laboratory findings [within 4 hours after surgery]
activated partial thromboplastin time (aPTT)
laboratory findings [postoperatively, 1 day after surgery]
White blood count
laboratory findings [postoperatively, 1 day after surgery]
C-reactive protein
laboratory findings [postoperatively, 1 day after surgery]
Procalcitonin
laboratory findings [postoperatively, 1 day after surgery]
Interleukin 6
laboratory findings [postoperatively, 1 day after surgery]
D-Dimer
laboratory findings [postoperatively, 1 day after surgery]
platelet count
laboratory findings [postoperatively, 1 day after surgery]
International normalized ratio (INR)
laboratory findings [postoperatively, 1 day after surgery]
activated partial thromboplastin time (aPTT)
postoperative AEP [up to 8 days after surgery]
Auditory evoked potentials after surgery
postoperative vertigo [up to 8 days after surgery]
Vertigo according to dizziness handicap inventory (=DHI, score 0-100, higher scores are associated with a higher burden of dizziness)
postoperative vertigo [3 months (± 6 weeks) after surgery]
Vertigo according to dizziness handicap inventory (=DHI, score 0-100, higher scores are associated with a higher burden of dizziness)
extent of schwannoma resection [3 months (± 6 weeks) after surgery]
extent of schwannoma resection on the postoperative MRI

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 years
total or gross-total resection of a vestibular schwannoma is planned
Functional hearing is still present on the affected side preoperatively (AEP evocable and Gardner-Robertson grade I, II, or III).
Preoperatively, facial function is unimpaired or mildly impaired (House and Brackmann grade I or II).

Exclusion Criteria:

Symptomatic peripheral artery disease.
Active or previous thrombosis in the extremity where the RIC procedure is to be performed.
Neurofibromatosis type 2
Only planned decompression of the internal auditory canal without relevant tumor resection
Pregnant or breastfeeding females
Previous radiotherapy of the vestibular schwannoma that will be resected

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital Tuebingen	Tuebingen		Germany	72076

Sponsors and Collaborators

University Hospital Tuebingen

Investigators

Principal Investigator: Contantin Roder, Prof., MD, Department of Neurosurgery Tuebingen
Principal Investigator: Helene V Hurth, MD, Department of Neurosurgery Tuebingen