Levetiracetam Compared to Magnesium Sulfate for Prevention of Eclamptic Seizure

Summary

The goal of this study is to compare levetiracetam to magnesium sulfate for the prevention of eclamptic seizures in pregnant persons with severe preeclampsia that are 32 or more weeks pregnant. This is an equivalence study so our primary goal is to see no difference in the incidence of seizure in the two groups. Since side effects can be a significant problem with magnesium sulfate and these patients are at significant risk of life threatening complications, we also plan to evaluate several secondary outcomes in the mothers and the babies, including: severe allergic reaction, magnesium toxicity, ICU admission, hospital readmission, transfusion for any reason, pulmonary edema, cardiomyopathy, Posterior Reversible Encephalopathy Syndrome, eclamptic seizure, loss of vision, stroke, renal injury requiring dialysis, cardiac arrest, maternal death, unexpected stillbirth or neonatal death, NICU admission, Apgars and length of neonatal respiratory support.

Timeline

Start

2026-01-01

Primary completion

2033-12-31

Completion

2034-07

Publications

• Background Johannessen Landmark C, Patsalos PN. Drug interactions involving the new second- and third-generation antiepileptic drugs. Expert Rev Neurother. 2010 Jan;10(1):119-40. doi: 10.1586/ern.09.136.
• Background Loscher W, Schmidt D. New Horizons in the development of antiepileptic drugs: Innovative strategies. Epilepsy Res. 2006 Jun;69(3):183-272. doi: 10.1016/j.eplepsyres.2006.03.014.
• Background Perucca P, Gilliam FG. Adverse effects of antiepileptic drugs. Lancet Neurol. 2012 Sep;11(9):792-802. doi: 10.1016/S1474-4422(12)70153-9. Epub 2012 Jul 24.
• Background French JA, Kanner AM, Bautista J, Abou-Khalil B, Browne T, Harden CL, Theodore WH, Bazil C, Stern J, Schachter SC, Bergen D, Hirtz D, Montouris GD, Nespeca M, Gidal B, Marks WJ Jr, Turk WR, Fischer JH, Bourgeois B, Wilner A, Faught RE Jr, Sachdeo RC, Beydoun A, Glauser TA; American Academy of Neurology Therapeutics and Technology Assessment Subcommittee; American Academy of Neurology Quality Standards Subcommittee; American Epilepsy Society Quality Standards Subcommittee; American Epilepsy Society Therapeutics and Technology Assessment Subcommittee. Efficacy and tolerability of the new antiepileptic drugs, I: Treatment of new-onset epilepsy: report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy Society. Epilepsia. 2004 May;45(5):401-9. doi: 10.1111/j.0013-9580.2004.06204.x.
• Background Patsalos PN. Clinical pharmacokinetics of levetiracetam. Clin Pharmacokinet. 2004;43(11):707-24. doi: 10.2165/00003088-200443110-00002.
• Background Kanner AM, Ashman E, Gloss D, Harden C, Bourgeois B, Bautista JF, Abou-Khalil B, Burakgazi-Dalkilic E, Llanas Park E, Stern J, Hirtz D, Nespeca M, Gidal B, Faught E, French J. Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new-onset epilepsy: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2018 Jul 10;91(2):74-81. doi: 10.1212/WNL.0000000000005755. Epub 2018 Jun 13.
• Background Appleton RE, Rainford NE, Gamble C, Messahel S, Humphreys A, Hickey H, Woolfall K, Roper L, Noblet J, Lee E, Potter S, Tate P, Al Najjar N, Iyer A, Evans V, Lyttle MD. Levetiracetam as an alternative to phenytoin for second-line emergency treatment of children with convulsive status epilepticus: the EcLiPSE RCT. Health Technol Assess. 2020 Nov;24(58):1-96. doi: 10.3310/hta24580.
• Background Shorvon SD, Lowenthal A, Janz D, Bielen E, Loiseau P. Multicenter double-blind, randomized, placebo-controlled trial of levetiracetam as add-on therapy in patients with refractory partial seizures. European Levetiracetam Study Group. Epilepsia. 2000 Sep;41(9):1179-86. doi: 10.1111/j.1528-1157.2000.tb00323.x.
• Background Ben-Menachem E, Falter U. Efficacy and tolerability of levetiracetam 3000 mg/d in patients with refractory partial seizures: a multicenter, double-blind, responder-selected study evaluating monotherapy. European Levetiracetam Study Group. Epilepsia. 2000 Oct;41(10):1276-83. doi: 10.1111/j.1528-1157.2000.tb04605.x.
• Background Chamberlain JM, Kapur J, Shinnar S, Elm J, Holsti M, Babcock L, Rogers A, Barsan W, Cloyd J, Lowenstein D, Bleck TP, Conwit R, Meinzer C, Cock H, Fountain NB, Underwood E, Connor JT, Silbergleit R; Neurological Emergencies Treatment Trials; Pediatric Emergency Care Applied Research Network investigators. Efficacy of levetiracetam, fosphenytoin, and valproate for established status epilepticus by age group (ESETT): a double-blind, responsive-adaptive, randomised controlled trial. Lancet. 2020 Apr 11;395(10231):1217-1224. doi: 10.1016/S0140-6736(20)30611-5. Epub 2020 Mar 20.
• Background Hope OA, Harris KM. Management of epilepsy during pregnancy and lactation. BMJ. 2023 Sep 8;382:e074630. doi: 10.1136/bmj-2022-074630.
• Background Carosella CM, Johnson EL. Special Issues in Medical Management: Hormones and Pregnancy in Epilepsy. Semin Neurol. 2025 Apr;45(2):198-205. doi: 10.1055/a-2551-0688. Epub 2025 Apr 3.
• Background Tomson T, Battino D, Bonizzoni E, Craig J, Lindhout D, Perucca E, Sabers A, Thomas SV, Vajda F; EURAP Study Group. Comparative risk of major congenital malformations with eight different antiepileptic drugs: a prospective cohort study of the EURAP registry. Lancet Neurol. 2018 Jun;17(6):530-538. doi: 10.1016/S1474-4422(18)30107-8. Epub 2018 Apr 18.
• Background Meador KJ, Pennell PB, Harden CL, Gordon JC, Tomson T, Kaplan PW, Holmes GL, French JA, Hauser WA, Wells PG, Cramer JA; HOPE Work Group. Pregnancy registries in epilepsy: a consensus statement on health outcomes. Neurology. 2008 Sep 30;71(14):1109-17. doi: 10.1212/01.wnl.0000316199.92256.af. Epub 2008 Aug 13.
• Background Mawhinney E, Craig J, Morrow J, Russell A, Smithson WH, Parsons L, Morrison PJ, Liggan B, Irwin B, Delanty N, Hunt SJ. Levetiracetam in pregnancy: results from the UK and Ireland epilepsy and pregnancy registers. Neurology. 2013 Jan 22;80(4):400-5. doi: 10.1212/WNL.0b013e31827f0874. Epub 2013 Jan 9.
• Background Shallcross R, Bromley RL, Cheyne CP, Garcia-Finana M, Irwin B, Morrow J, Baker GA; Liverpool and Manchester Neurodevelopment Group; UK Epilepsy and Pregnancy Register. In utero exposure to levetiracetam vs valproate: development and language at 3 years of age. Neurology. 2014 Jan 21;82(3):213-21. doi: 10.1212/WNL.0000000000000030. Epub 2014 Jan 8.
• Background Shallcross R, Bromley RL, Irwin B, Bonnett LJ, Morrow J, Baker GA; Liverpool Manchester Neurodevelopment Group; UK Epilepsy and Pregnancy Register. Child development following in utero exposure: levetiracetam vs sodium valproate. Neurology. 2011 Jan 25;76(4):383-9. doi: 10.1212/WNL.0b013e3182088297.
• Background Chaudhry SA, Jong G, Koren G. The fetal safety of Levetiracetam: a systematic review. Reprod Toxicol. 2014 Jul;46:40-5. doi: 10.1016/j.reprotox.2014.02.004. Epub 2014 Mar 3.

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Indications