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. 2021 Apr 15;22(1):285.
doi: 10.1186/s13063-021-05208-6.

Stereotactic cisternal lavage in patients with aneurysmal subarachnoid hemorrhage with urokinase and nimodipine for the prevention of secondary brain injury (SPLASH): study protocol for a randomized controlled trial

Roland Roelz #  1 , Fabian Schubach #  2 , Volker A Coenen  3 , Carolin Jenkner  4 , Christian Scheiwe  1 , Jürgen Grauvogel  1 , Wolf-Dirk Niesen  5 , Horst Urbach  6 , Christian Taschner  6 , Jochen Seufert  7 , Jürgen Kätzler  8 , Jürgen Beck  1 , Peter C Reinacher  3   9
Affiliations

Stereotactic cisternal lavage in patients with aneurysmal subarachnoid hemorrhage with urokinase and nimodipine for the prevention of secondary brain injury (SPLASH): study protocol for a randomized controlled trial

Roland Roelz et al. Trials. .

Abstract

Background: Delayed cerebral infarction (DCI) is a major cause of death and poor neurological outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). Direct intrathecal therapies with fibrinolytic and spasmolytic drugs have appeared promising in clinical trials. However, access to the subarachnoid space for intrathecal drug administration is an unsolved problem so far, especially in patients with endovascular aneurysm securing. We investigate a therapy protocol based on stereotactic catheter ventriculocisternostomy (STX-VCS), a new approach to overcome this problem. The primary objective of this study is to assess whether cisternal lavage with urokinase, nimodipine, and Ringer's solution administered via a stereotactically implanted catheter into the basal cisterns (= investigational treatment (IT)) is safe and improves neurological outcome in patients with aSAH.

Methods: This is a randomized, controlled, parallel-group, open-label phase II trial. Fifty-four patients with severe aSAH (WFNS grade ≥ 3) will be enrolled at one academic tertiary care center in Southern Germany. Patients will be randomized at a ratio of 1:1 to receive either standard of care only or standard of care plus the IT. The primary endpoint is the proportion of subjects with a favorable outcome on the Modified Rankin Scale (defined as mRS 0-3) at 6 months after aSAH. Further clinical and surrogate outcome parameters are defined as secondary endpoints.

Discussion: New approaches for the prevention and therapy of secondary brain injury in patients with aSAH are urgently needed. We propose this RCT to assess the clinical safety and efficacy of a novel therapy protocol for intrathecal administration of urokinase, nimodipine, and Ringer's solution.

Trial registration: Deutsches Register Klinischer Studien (German Clinical Trials Register), DRKS00015645 . Registered on 8 May 2019.

Keywords: Aneurysmal subarachnoid hemorrhage (aSAH); Clinical trial; Delayed cerebral infarction (DCI); Intracisternal lavage; Intrathecal treatment; Nimodipine; Stereotactic ventriculocisternostomy (STX-VCS); Urokinase.

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Conflict of interest statement

Dr. Roelz and Dr. Reinacher report a research grant from Else Kröner-Fresenius-Stiftung for the conduct of the study. Dr. Reinacher reports personal fees from Fraunhofer-Gesellschaft (Munich, Germany), Boston Scientific (Marlborough, MA, USA), Brainlab (Munich, Germany), and Inomed (Emmendingen, Germany) outside the submitted work. The other authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Study design
Fig. 2
Fig. 2
Therapy protocol in group 2
Fig. 3
Fig. 3
Setup of investigational treatment administration. Arrows indicate the flow direction of the lavage solution
See this image and copyright information in PMC

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