Prevention of Vasospasm in SAH Through CSF Treatment

NCT04490161 | Recruiting DMC

• 1 other identifier: 1193/2018
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The pathophysiological mechanisms of aneurysmal subarachnoid haemorrhage (aSAH) involve early brain injury (EBI) and delayed cerebral ischemia (DCI). Several mechanisms contribute to EBI pathogenesis, including cell death, inflammatory response, oxidative stress, excitotoxicity, microcirculatory dysfunction, microthrombosis and cortical spreading depolarization. All are suggested to be linked due to common pathogenic pathways and direct interaction. Despite advances in research of diagnostics and treatment strategies, brain injury remains the major cause of death and disability in SAH patients. There is no sufficient treatment of SAH and its devastating consequences known so far. Developing and improving diagnostic methods to monitor SAH patients and to evaluate efficacy of treatment strategies are essential in SAH research. These include neuroimaging, biomarkers, and other parameters such as invasive multimodal neuromonitoring and intraoperative electrophysiological monitoring. Cerebral vasospasm (CV) - mostly responsible for DCI - can be depicted on angiograms. Altogether, tremendous efforts have been taken to conquer the occurrence and sustainability of CV. The mortality of patients suffering aSAH rises up to 50% if the patients' condition is critical (Hunt\&Hess (HH) Grade 5, WFNS Grade 5, modified Fisher Grade 4). Reports of beneficial outcome in patients with pre-existing CSF shunting have been published. The hypothesis of early CSF reapplication to the bloodstream, in order to prevent CV seems to be positively approved by the mentioned reports. Nevertheless, no data could be found on the mechanisms of action in this phenomenon. To confirm the presence of interaction of the mechanisms of EBI and evaluate the application of cerebrospinal fluid (CSF), a pilot clinical trial was planned. Due to the lack of validated animal models for aSAH it is necessary to perform the trial first-in-human. A pilot (proof of concept) trial - is done through inclusion of 10 patients with severe aSAH (≥HH4). According to clinical guidelines, these patients receive external ventricular drainages in order to drain CSF and lower intracranial pressure. An interim analysis of data will be performed after inclusion and treatment of 5 patients. Blood-/CSF-sampling for further analysis will be collected before, during and after treatment according to the study protocol.

Conditions

Subarachnoid Hemorrhage; Subarachnoid Hemorrhage, Aneurysmal; Vasospasm, Cerebral; Aneurysmal Subarachnoid Hemorrhage

Keywords

EVD; Aneurysm; SAH; Subarachnoid hemorrhage; cerebral vasospasm; cerebrospinal fluid

Outcome Measures

Primary Outcomes (1)

• Incidence of severe radiographic vasospasm

  measured upon digital subtraction angiography

  8 (+/- 1) day post SAH

Secondary Outcomes (2)

• Infectious complications

  7 days

• Incidence of vasospasm-related morbidity / mortality

  within 21 days post-aneurysm securing

Study Arms (2)

Interventional

EXPERIMENTAL

Subjects will receive reinstallation of CSF intravenously.

Other: intravenous reinstallation of cerebrospinal fluid

Observational

NO INTERVENTION

Subjects will not receive study intervention; CSF will be sampled and analyzed in comparison to the Interventional arm,

Interventions

intravenous reinstallation of cerebrospinal fluid OTHER

10ml of CSF will be taken under sterile conditions from the external ventricular drain and immediately administered intravenously.

Interventional

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: \>18, \<90
• SAH HH 3 - 5
• Cerebral saccular Aneurysm
• Digital subtraction angiography prior to aneurysm repair
• Aneurysm repair within 72h
• Modified Fisher Grade 3+4
• Presence of aneurysm needing treatment (clipping or coiling)
• Treatment within 24 hours of symptom onset
• External ventricular drain (clinical need)

You may not qualify if:

• Non-aneurysmal SAH
• SAH HH\<3
• Extensive intraventricular haemorrhage (unable to obtain CSF without massive aspiration of clotted blood)
• Contraindication for digital subtraction angiography
• Aneurysm repair \>72h after rupture
• Signs of radiographic vasospasm upon diagnosis
• Presence of systemic or CSF infection
• Contraindication for oral Nimodipin
• Pregnancy

Sponsors & Collaborators

• Medical University Innsbruck: lead

Study Sites (1)

Medical University of Innsbruck

Innsbruck, Tyrol, 6020, Austria

RECRUITING

Related Publications (9)

• de Rooij NK, Linn FH, van der Plas JA, Algra A, Rinkel GJ. Incidence of subarachnoid haemorrhage: a systematic review with emphasis on region, age, gender and time trends. J Neurol Neurosurg Psychiatry. 2007 Dec;78(12):1365-72. doi: 10.1136/jnnp.2007.117655. Epub 2007 Apr 30.

  PMID: 17470467 BACKGROUND

• Nieuwkamp DJ, Setz LE, Algra A, Linn FH, de Rooij NK, Rinkel GJ. Changes in case fatality of aneurysmal subarachnoid haemorrhage over time, according to age, sex, and region: a meta-analysis. Lancet Neurol. 2009 Jul;8(7):635-42. doi: 10.1016/S1474-4422(09)70126-7. Epub 2009 Jun 6.

  PMID: 19501022 BACKGROUND

• Kreiter KT, Copeland D, Bernardini GL, Bates JE, Peery S, Claassen J, Du YE, Stern Y, Connolly ES, Mayer SA. Predictors of cognitive dysfunction after subarachnoid hemorrhage. Stroke. 2002 Jan;33(1):200-8. doi: 10.1161/hs0102.101080.

  PMID: 11779911 BACKGROUND

• Connolly ES Jr, Rabinstein AA, Carhuapoma JR, Derdeyn CP, Dion J, Higashida RT, Hoh BL, Kirkness CJ, Naidech AM, Ogilvy CS, Patel AB, Thompson BG, Vespa P; American Heart Association Stroke Council; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; Council on Cardiovascular Surgery and Anesthesia; Council on Clinical Cardiology. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/american Stroke Association. Stroke. 2012 Jun;43(6):1711-37. doi: 10.1161/STR.0b013e3182587839. Epub 2012 May 3.

  PMID: 22556195 BACKGROUND

• Langham J, Reeves BC, Lindsay KW, van der Meulen JH, Kirkpatrick PJ, Gholkar AR, Molyneux AJ, Shaw DM, Copley L, Browne JP; Steering Group for National Study of Subarachnoid Haemorrhage. Variation in outcome after subarachnoid hemorrhage: a study of neurosurgical units in UK and Ireland. Stroke. 2009 Jan;40(1):111-8. doi: 10.1161/STROKEAHA.108.517805. Epub 2008 Nov 13.

  PMID: 19008474 BACKGROUND

• Pickard JD, Murray GD, Illingworth R, Shaw MD, Teasdale GM, Foy PM, Humphrey PR, Lang DA, Nelson R, Richards P, et al. Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial. BMJ. 1989 Mar 11;298(6674):636-42. doi: 10.1136/bmj.298.6674.636.

  PMID: 2496789 BACKGROUND

• Dorhout Mees SM, Rinkel GJ, Feigin VL, Algra A, van den Bergh WM, Vermeulen M, van Gijn J. Calcium antagonists for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev. 2007 Jul 18;2007(3):CD000277. doi: 10.1002/14651858.CD000277.pub3.

  PMID: 17636626 BACKGROUND

• Vergouwen MD; Participants in the International Multi-Disciplinary Consensus Conference on the Critical Care Management of Subarachnoid Hemorrhage. Vasospasm versus delayed cerebral ischemia as an outcome event in clinical trials and observational studies. Neurocrit Care. 2011 Sep;15(2):308-11. doi: 10.1007/s12028-011-9586-8.

  PMID: 21748502 BACKGROUND

• Vergouwen MD, Vermeulen M, van Gijn J, Rinkel GJ, Wijdicks EF, Muizelaar JP, Mendelow AD, Juvela S, Yonas H, Terbrugge KG, Macdonald RL, Diringer MN, Broderick JP, Dreier JP, Roos YB. Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group. Stroke. 2010 Oct;41(10):2391-5. doi: 10.1161/STROKEAHA.110.589275. Epub 2010 Aug 26.

  PMID: 20798370 BACKGROUND

MeSH Terms

Conditions

Subarachnoid Hemorrhage; Vasospasm, Intracranial; Aneurysm

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Christian F Freyschlag, MD

CONTACT

+4350504; christian.freyschlag@i-med.ac.at

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2020
• First Posted: July 28, 2020
• Study Start: January 1, 2020
• Primary Completion: February 1, 2025
• Study Completion: February 1, 2025
• Last Updated: November 27, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)