Labetalol Versus Magnesium Sulfate (MgSO4) for the Prevention of Eclampsia Trial
Status:
Withdrawn
Trial end date:
2017-01-01
Target enrollment:
Participant gender:
Summary
Eclampsia is a major cause of perinatal morbidity and mortality. The pathophysiology is not
known but magnetic resonance imaging (MRI) and Doppler data suggest that overperfusion of the
cerebral tissues is a major etiologic factor. Hypertensive encephalopathy from overperfusion,
and vascular damage from excessive arterial pressure (cerebral barotrauma) are believed to
lead to vasogenic and cytotoxic cerebral edema, with resultant neuronal anomalies, seizure
activity and cerebral bleeding if left unchecked. Doppler data have shown that cerebral
perfusion pressure (CPP) is abnormally increased in severe preeclampsia and that
autoregulation of the middle cerebral artery is affected by this condition leading to
increased CPP. Magnesium sulfate (MgSO4) is the most widely accepted eclampsia treatment and
prophylactic agent, and it has been used in the USA since the 1950's. Despite widespread use,
its mechanism of action is unknown. MgSO4 is given intravenously or intramuscularly and
requires specialized nursing training and monitoring to minimize toxicity from respiratory
and cardiac depression. Labetalol, a combined alpha and beta blocker, has been used for many
years to safely treat hypertension in preeclamptic women, and is now known to reduce CPP in
women with preeclampsia. In the United Kingdom labetalol was for many years used as the sole
agent in treating preeclampsia, and the rate of seizure was no different to that reported in
the USA with MgSO4. Since labetalol can be administered orally, is economical, has low
toxicity potential, does not require specialized training to administer or monitor, and
decreases CPP, it may be an ideal agent for controlling blood pressure (BP) and decreasing
the incidence of eclampsia in women with preeclampsia. The current study is a multicenter,
randomized, controlled trial to compare the anti-seizure effect of parenteral MgSO4 versus
oral labetalol in hypertensive pregnant women who are eligible for MgSO4 therapy. The primary
outcome measure is eclampsia, and the secondary outcome measures include blood pressure
control, and relevant antenatal, intrapartum, and postnatal maternal and fetal/neonatal
parameters including adverse effects and complications. Inclusion criteria are deliberately
broad in order to make the study clinically relevant. Hypertensive pregnant women, in whom
the decision for delivery has been made, will be enrolled after written, informed consent.
Patients will be randomized to receive MgSO4 therapy as given in their institution, versus
oral labetalol (200mg/q6 hours), from enrollment in the study until 24 hours post delivery.
There will be 4000 patients in each arm of the study and analysis will be by
intention-to-treat. The study is powered to show both therapeutic superiority as well as
clinical equivalence. This study has the potential to change the way preeclampsia is managed,
and will represent a major advance in terms of the availability and safety of prophylactic
therapy, especially in developing nations where MgSO4 is underutilized due to cost
constraints.