Seizure Prophylaxis With Levetiracetam in Aneurysmal Subarachnoid Hemorrhage - Pilot Study

Subarachnoid Hemorrhage Clinical Trial

— SPLASH - Pilot  

Official title:

Pilot Study of Seizure Prophylaxis With Levetiracetam in Aneurysmal Subarachnoid Hemorrhage

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01935908
• Other study ID #: SPLASH-P1
• Status: Withdrawn
• Phase: Phase 4
• First received: April 21, 2013
• Last updated: October 30, 2017
• Start date: May 2013
• Est. completion date: May 2013

Study information

• Verified date: October 2017
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the feasibility of prospectively enrolling and randomizing patients with aneurysmal subarachnoid hemorrhage (aSAH) to receive levetiracetam or not to receive levetiracetam, and documenting in-hospital and follow-up clinical variables.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: May 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• = 18 years of age

• = 75 years of age

• Newly diagnosed aneurysmal subarachnoid hemorrhage

Exclusion Criteria:

• One or more antiepileptic medication is taken as a pre-admission medication

• Seizure occurrence in the field or in the emergency department, or anytime before consent could be obtained

• Inability to obtain informed consent from the patient, or from the patient's appropriate surrogate

Related Conditions & MeSH terms

• Hemorrhage
• Seizures
• Subarachnoid Hemorrhage

Intervention

Drug:
• levetiracetam

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (18)

Beeton AG, Upton PM, Shipton EA. The case for patient-controlled analgesia. Inter-patient variation in postoperative analgesic requirements. S Afr J Surg. 1992 Mar;30(1):5-6. — View Citation

Butzkueven H, Evans AH, Pitman A, Leopold C, Jolley DJ, Kaye AH, Kilpatrick CJ, Davis SM. Onset seizures independently predict poor outcome after subarachnoid hemorrhage. Neurology. 2000 Nov 14;55(9):1315-20. — View Citation

Choi KS, Chun HJ, Yi HJ, Ko Y, Kim YS, Kim JM. Seizures and Epilepsy following Aneurysmal Subarachnoid Hemorrhage : Incidence and Risk Factors. J Korean Neurosurg Soc. 2009 Aug;46(2):93-8. doi: 10.3340/jkns.2009.46.2.93. Epub 2009 Aug 31. — View Citation

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. — View Citation

Hart RG, Byer JA, Slaughter JR, Hewett JE, Easton JD. Occurrence and implications of seizures in subarachnoid hemorrhage due to ruptured intracranial aneurysms. Neurosurgery. 1981 Apr;8(4):417-21. — View Citation

Hovinga CA. Levetiracetam: a novel antiepileptic drug. Pharmacotherapy. 2001 Nov;21(11):1375-88. Review. — View Citation

Kvam DA, Loftus CM, Copeland B, Quest DO. Seizures during the immediate postoperative period. Neurosurgery. 1983 Jan;12(1):14-7. — View Citation

Lin CL, Dumont AS, Lieu AS, Yen CP, Hwang SL, Kwan AL, Kassell NF, Howng SL. Characterization of perioperative seizures and epilepsy following aneurysmal subarachnoid hemorrhage. J Neurosurg. 2003 Dec;99(6):978-85. — View Citation

Little AS, Kerrigan JF, McDougall CG, Zabramski JM, Albuquerque FC, Nakaji P, Spetzler RF. Nonconvulsive status epilepticus in patients suffering spontaneous subarachnoid hemorrhage. J Neurosurg. 2007 May;106(5):805-11. — View Citation

Mink S, Muroi C, Seule M, Bjeljac M, Keller E. Levetiracetam compared to valproic acid: plasma concentration levels, adverse effects and interactions in aneurysmal subarachnoid hemorrhage. Clin Neurol Neurosurg. 2011 Oct;113(8):644-8. doi: 10.1016/j.clineuro.2011.05.007. Epub 2011 Jun 23. — View Citation

Molyneux AJ, Kerr RS, Yu LM, Clarke M, Sneade M, Yarnold JA, Sandercock P; International Subarachnoid Aneurysm Trial (ISAT) Collaborative Group. International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion. Lancet. 2005 Sep 3-9;366(9488):809-17. — View Citation

Murphy-Human T, Welch E, Zipfel G, Diringer MN, Dhar R. Comparison of short-duration levetiracetam with extended-course phenytoin for seizure prophylaxis after subarachnoid hemorrhage. World Neurosurg. 2011 Feb;75(2):269-74. doi: 10.1016/j.wneu.2010.09.002. — View Citation

Rhoney DH, Tipps LB, Murry KR, Basham MC, Michael DB, Coplin WM. Anticonvulsant prophylaxis and timing of seizures after aneurysmal subarachnoid hemorrhage. Neurology. 2000 Jul 25;55(2):258-65. — View Citation

Rosengart AJ, Huo JD, Tolentino J, Novakovic RL, Frank JI, Goldenberg FD, Macdonald RL. Outcome in patients with subarachnoid hemorrhage treated with antiepileptic drugs. J Neurosurg. 2007 Aug;107(2):253-60. — View Citation

Shah D, Husain AM. Utility of levetiracetam in patients with subarachnoid hemorrhage. Seizure. 2009 Dec;18(10):676-9. doi: 10.1016/j.seizure.2009.09.003. Epub 2009 Oct 27. — View Citation

Sundaram MB, Chow F. Seizures associated with spontaneous subarachnoid hemorrhage. Can J Neurol Sci. 1986 Aug;13(3):229-31. — View Citation

Szaflarski JP, Sangha KS, Lindsell CJ, Shutter LA. Prospective, randomized, single-blinded comparative trial of intravenous levetiracetam versus phenytoin for seizure prophylaxis. Neurocrit Care. 2010 Apr;12(2):165-72. doi: 10.1007/s12028-009-9304-y. — View Citation

Usami K, Saito N. Prophylactic anticonvulsants after subarachnoid hemorrhage. World Neurosurg. 2011 Feb;75(2):214. doi: 10.1016/j.wneu.2010.09.035. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	modified Rankin Scale (mRS)	mRS - modified Rankin Scale (0-6): 0 - no symptoms; - no significant disability. Able to carry out all usual activities, despite some symptoms; - slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities; - moderate disability. Requires some help, but able to walk unassisted.; - moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.; - Severe disability. Requires constant nursing care and attention, bedridden, incontinent.; - dead	hospital discharge, 1-month, 3-months
Other	Glasgow Outcomes Scale-Extended (GOSE)	GOSE - Glasgow Outcomes Scale - Extended (1-8): - death; - vegetative state; - lower severe disability; - upper severe disability; - lower moderate disability; - upper moderate disability; - lower good recovery; - upper good recovery	hospital discharge, 1-month, 3-month
Primary	Randomization Yield	The primary outcome will be the number of patients randomized to either levetiracetam administration or no administration of levetiracetam divided by the total number of aneurysmal subarachnoid hemorrhage patients who present to the Vanderbilt University Emergency Department or are directly admitted to the Neuro Intensive Care Unit. (Unit of Measure: numeric fraction)	6 months
Secondary	Protocol Adherence Yield	The Protocol Adherence Yield is calculated by dividing the number of patients completing the study without incurring a protocol deviation by the total number of patients randomized. (Unit of Measure: numeric fraction)	9 months