A Phase 3 interventional study of Levetiracetam and magnesium sulfate in Severe Preeclampsia and Eclampsia Preeclampsia, sponsored by Nebraska Methodist Health System. Not yet recruiting at 1 site in United States. Open to female participants aged 19 Years and older. Per ClinicalTrials.gov, last updated 2025-10-24.
Sponsored by Nebraska Methodist Health System · Phase 3, Interventional, and Prevention
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.
Levetiracetam Compared to Magnesium Sulfate for Prevention of Eclamptic Seizure: A Randomized Controlled Trial Study Protocol
Objectives
Study Design
Study Population
Inclusion Criteria:
Exclusion Criteria:
Intervention/Comparator
Outcome Measures
Primary Outcome:
o Incidence of eclamptic seizures from enrollment to discharge from delivery hospitalization.
Secondary Outcomes:
Sample Size and Power Calculation
Randomization Technique
Enrollment
Adverse Event Reporting
Ethical Considerations and Informed Consent
Study Justification and Protocol Clarifications Modern anti-epileptic drugs have not been evaluated in their ability to prevent eclamptic seizures. The last studies comparing magnesium sulfate were performed against Nimodipine, a calcium channel blocker, over 20 years ago and phenytoin around 30 years ago. Magnesium sulfate is the current gold standard for seizure prophylaxis in women with hypertensive disease of pregnancy. It is a high risk medication that requires careful management and titration due to the risk for toxicity, respiratory depression, cardiac arrhythmia and death. Despite the high risk nature of a magnesium drip there has not been recent effort to identify safer medications for the prevention of eclamptic seizures. The study authors advocate for the study of Levetiracetam commercially known as Keppra®.
Levetiracetam is FDA approved for tonic-clonic seizures and is already used during pregnancy with an excellent safety profile in women with epilepsy (see appendix A). Use in this trial would be short term (likely 36-96 hours) and in late preterm or term pregnancies. This poses no risk for fetal malformation or birth defects as organogenesis is completed by 12 weeks and the study will enroll patients after 32 weeks gestation. As noted, levetiracetam has demonstrated safety in pregnancy in women with epilepsy and is safe in women who are breastfeeding. It has few significant complications specific to the medication itself and the short-term nature of the use in this study further mitigates those risks. Immediate release levetiracetam reaches maximum concentration in the blood in approximately 1 hour. Magnesium sulfate reaches a peak in 30 minutes when a bolus is given with levels falling by 60 minutes to roughly 2x physiologic levels, but typically below the 2mmol/L that is academically thought to be therapeutic. There is no currently established therapeutic dose based on scientific data. It is not recommended to routinely check magnesium levels during infusion unless there is concern for toxicity or renal impairment.
Inclusion/Exclusion - the reasoning behind our various criteria are related to state law, drug metabolism and to prevent confounders. Patients under 32 weeks gestation are excluded as they should receive magnesium sulfate for fetal neuroprotection and this exposure would confound the exposure groups, 19 y/o is the age of consent in Nebraska and renal impairment is important as both magnesium sulfate and levetiracetam are renally cleared. Since magnesium is rapidly cleared from the body we are choosing to include patients with less than 2 hours of exposure to magnesium or who have not received magnesium in the last 48 hours as we feel this does not clinically confound results due to short duration of exposure or complete clearance of the medication after prior exposure.
Dosing for magnesium is based on medically standardized protocol and Levetiracetam dosing is based on adult dosing in non-pregnant individuals with tonic-clonic seizures.
916 studies on the registry are indexed under Pre-Eclampsia; 243 are open to participants now.
This study's planned enrollment of 1,240 is above the median of 110 across 480 interventional studies indexed under Pre-Eclampsia.
Browse Pre-Eclampsia studies →Nebraska Methodist Health System is the lead sponsor of 5 studies on the registry; 3 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
This experimental arm will receive oral levetiracetam 3 times daily after an initial loading oral dose.
Drug: Levetiracetam
This arm will receive standard treatment- a loading dose of magnesium sulfate followed by a continuous infusion that is the current standard of care (4 gram bolus followed by 2grams per hour continuous infusion).
Drug: magnesium sulfate
1g oral loading dose followed by 300mg q 8 hours beginning 8 hours after loading dose.
Also known as: Keppra
4gram bolus followed by 2g per hour continuous infusion
Eclamptic Seizure
Seizure based on clinical diagnosis by managing physician. It will be considered and eclamptic seizure for purposes of the study if it occurs following enrollment in the study.
Time frame: From enrollment until then end of monitoring at 6 weeks postpartum.
Plan to share: Yes — Deidentified IPD will be shared on a case-by-case basis.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form
Time frame: IPD will be shared beginning 1 year after publication.
Access criteria: Deidentified IPD will be shared on a case by case basis with principal investigators by contacting the PI for this study.
Start is estimated for Jan 2026; primary completion for Dec 2033, 95 months later.
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Studies of the drug tested here: Levetiracetam
Nebraska Methodist Health System