Labetalol Versus Magnesium Sulfate (MgSO4) for the Prevention of Eclampsia Trial

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.

Conditions

• Preeclampsia
• Pregnancy Induced Hypertension
• Gestational Hypertension
• Chronic Hypertension
• Superimposed Preeclampsia

Interventions

DRUG

labetalol (seizure prevention)

20mg IV (can be increased to an escalating dose of maximum of 80 mg (20mg, 40 mg, 80 mg q 20min) Cumulative max of 240 mg. 20mg labetalol PO every 6 hours

DRUG

MgSO4 (seizure prevention)

4-6g bolus over 20 minutes; 1-2 grams/hr Discontinued 24 hours after delivery.

Sponsors & Collaborators

• Baylor College of Medicine

  lead OTHER

Principal Investigators

• Michael A Belfort, MD, PhD · Baylor College of Medicine

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

15 Years

Max Age

60 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2015-06-30

Primary Completion

2017-01-31

Completion

2017-01-31

Countries

• United States
• India

Study Locations