Prophylactic nimodipine treatment for cochlear and facial nerve preservation after vestibular schwannoma surgery: a randomized multicenter Phase III trial.
OBJECTIVE
A pilot study of prophylactic nimodipine and hydroxyethyl starch treatment showed a beneficial effect on facial and cochlear nerve preservation following vestibular schwannoma (VS) surgery. A prospective Phase III trial was undertaken to confirm these results.


METHODS
An open-label, 2-arm, randomized parallel group and multicenter Phase III trial with blinded expert review was performed and included 112 patients who underwent VS surgery between January 2010 and February 2013 at 7 departments of neurosurgery to investigate the efficacy and safety of the prophylaxis. The surgery was performed after the patients were randomly assigned to one of 2 groups using online randomization. The treatment group (n = 56) received parenteral nimodipine (1-2 mg/hr) and hydroxyethyl starch (hematocrit 30%-35%) from the day before surgery until the 7th postoperative day. The control group (n = 56) was not treated prophylactically.


RESULTS
Intent-to-treat analysis showed no statistically significant effects of the treatment on either preservation of facial nerve function (35 [67.3%] of 52 [treatment group] compared with 34 [72.3%] of 47 [control group]) (p = 0.745) or hearing preservation (11 [23.4%] of 47 [treatment group] compared with 15 [31.2%] of 48 [control group]) (p = 0.530) 12 months after surgery. Since tumor sizes were significantly larger in the treatment group than in the control group, logistic regression analysis was required. The risk for deterioration of facial nerve function was adjusted nearly the same in both groups (OR 1.07 [95% CI 0.34-3.43], p = 0.91). In contrast, the risk for postoperative hearing loss was adjusted 2 times lower in the treatment group compared with the control group (OR 0.49 [95% CI 0.18-1.30], p = 0.15). Apart from dose-dependent hypotension (p < 0.001), no clinically relevant adverse reactions were observed.


CONCLUSIONS
There were no statistically significant effects of the treatment. Despite the width of the confidence intervals, the odds ratios may suggest but do not prove a clinically relevant effect of the safe study medication on the preservation of cochlear nerve function after VS surgery. Further study is needed before prophylactic nimodipine can be recommended in VS surgery.
Departments of 1 Neurosurgery and.|Translational Centre for Regenerative Medicine, University of Leipzig;
Christian
C
Scheller
Institute of Medical Epidemiology, Biostatistics, and Informatics; and.
Andreas
A
Wienke
Department of Neurosurgery, University of Tübingen; 
Marcos
M
Tatagiba
Department of Neurosurgery, University of Tübingen; 
Alireza
A
Gharabaghi
Department of Neurosurgery, University of Tübingen; 
Kristofer F
KF
Ramina
Departments of 5 Neurosurgery.
Oliver
O
Ganslandt
Departments of 5 Neurosurgery.
Barbara
B
Bischoff
Otorhinolaryngology, Head and Neck Surgery, and.
Johannes
J
Zenk
Neuroradiology, University of Erlangen-Nuremberg;
Tobias
T
Engelhorn
Department of Neurosurgery, Würzburg University Hospital, Würzburg;
Cordula
C
Matthies
Department of Neurosurgery, Würzburg University Hospital, Würzburg;
Thomas
T
Westermaier
Department of Neurosurgery, Bezirkskrankenhaus Günzburg, University of Ulm;
Gregor
G
Antoniadis
Department of Neurosurgery, Bezirkskrankenhaus Günzburg, University of Ulm;
Maria Teresa
MT
Pedro
Department of Neurosurgery, University of Göttingen;
Veit
V
Rohde
Department of Neurosurgery, University of Göttingen;
Kajetan
K
von Eckardstein
Department of Neurosurgery, Evangelisches Krankenhaus, University of Oldenburg, Germany; and.
Thomas
T
Kretschmer
Neurology;
Malte
M
Kornhuber
Coordination Centre for Clinical Trials, University of Halle-Wittenberg, Halle (Saale);
Jörg
J
Steighardt
Coordination Centre for Clinical Trials, University of Halle-Wittenberg, Halle (Saale);
Michael
M
Richter
Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts.
Fred G
FG
Barker
Departments of 1 Neurosurgery and.
Christian
C
Strauss
D000328:Adult; D003056:Cochlear Nerve / Q000503:physiopathology; D020209:Cranial Nerve Injuries / Q000209:etiology / Q000517:prevention & control*; D005154:Facial Nerve / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009464:Neuroma, Acoustic / Q000601:surgery*; D009553:Nimodipine / Q000627:therapeutic use*; D011183:Postoperative Complications; D014665:Vasodilator Agents / Q000627:therapeutic use*
D014665:Vasodilator Agents; D009553:Nimodipine
HES = hydroxyethyl starch; VS = vestibular schwannoma; acoustic neuroma; neuroprotection; nimodipine; skull base; vestibular schwannoma