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

This study has suspended participant recruitment.
(Change of coordinating center to new institution.)
Sponsor:
Information provided by (Responsible Party):
Michael Belfort, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT00293735
First received: February 16, 2006
Last updated: January 29, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Preeclampsia
Pregnancy Induced Hypertension
Gestational Hypertension
Chronic Hypertension
Superimposed Preeclampsia
Drug: labetalol (seizure prevention)
Drug: MgSO4 (seizure prevention)
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Labetalol Versus MgSO4 for the Prevention of Eclampsia Trial (LAMPET)

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • Occurrence of eclamptic seizure(s) after enrollment in the study. [ Time Frame: 24 Hours Postpartum ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Maternal: Blood pressure, pulse pressure and heart rate changes [ Time Frame: 24 hours postpartum ] [ Designated as safety issue: Yes ]
  • Need for additional antihypertensive medication (defined by need to control BP > 160 mmHg systolic and/or 110 mmHg) [ Time Frame: 24 hours postpartum ] [ Designated as safety issue: Yes ]
  • Subjective assessment of side effects by the patient [ Time Frame: 24 hours postpartum ] [ Designated as safety issue: Yes ]
  • Objective assessment of new onset complications and/or side effects by the treating clinicians [ Time Frame: 24 hours postpartum ] [ Designated as safety issue: Yes ]
  • Labor and delivery parameters including; induction to delivery interval, rate of cervical dilatation, oxytocin dosages, length of labor, delivery route, blood loss at delivery, and postpartum course; and [ Time Frame: 24 hours postpartum ] [ Designated as safety issue: Yes ]
  • Type of anesthesia administered (none, local infiltration for delivery only, epidural for labor, epidural for delivery, spinal for delivery, combined/spinal epidural for labor and delivery, general anesthesia for delivery). [ Time Frame: 24 hours postpartum ] [ Designated as safety issue: Yes ]
  • Fetal and Neonatal: Occurrence of newly diagnosed fetal distress during labor necessitating emergent delivery [ Time Frame: 24 hour postpartum ] [ Designated as safety issue: Yes ]
  • Umbilical cord gases at delivery (if available in institution) [ Time Frame: 30 minutes after delivery ] [ Designated as safety issue: Yes ]
  • Apgar scores; and [ Time Frame: 1min and 5 minutes after delivery ] [ Designated as safety issue: Yes ]
  • Neonatal outcome as defined by NICU admission, hospital survival to discharge, length of hospital survival, days in NICU, need for blood transfusion, need for pressor agents, need for mechanical ventilation, neonatal cardiac dysrhythmias, [ Time Frame: Discharge from hospital ] [ Designated as safety issue: Yes ]
  • neonatal cardiac failure, necrotizing enterocolitis, sudden infant death, neonatal sepsis, neonatal hypoglycemia, and there will be an other block for recording any other identified complications not mentioned. [ Time Frame: discharge from hospital ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 8000
Study Start Date: June 2015
Estimated Study Completion Date: December 2020
Estimated Primary Completion Date: June 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1. Labetolol 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

Active Comparator: 2. Magnesium Sulfate Drug: MgSO4 (seizure prevention)
4-6g bolus over 20 minutes; 1-2 grams/hr Discontinued 24 hours after delivery.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   15 Years to 60 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Any patient with preeclampsia (BP > 140 systolic and/or > 90 mmHg diastolic with 1+ or more proteinuria [or a 24 hour specimen with > 300 mg/day]), chronic hypertension (or superimposed preeclampsia), or gestational hypertension deemed to be at risk for eclamptic convulsions and who would routinely be treated in the participating institution with some form of anti-seizure prophylaxis during labor and delivery.

Exclusion Criteria:

  • Any patient for whom informed consent cannot be obtained.
  • Any patient who has received an antihypertensive medication within 6 hours prior to enrollment will not be eligible but those who have received antihypertensive medications other than beta-blockers or magnesium sulfate may still be enrolled as long as they have not been given a dose within the 6 hours prior to enrollment. If a patient has received MgSO4 or a short acting beta-blocker or calcium channel blocker more than 12 hours prior to enrollment or if they have received a long acting beta-blocker more than 24 hours before enrollment she may still be considered eligible. This stipulation will allow increased recruitment of patients especially those with chronic hypertension and those transferred from outlying institutions. We expect these patients to be a minority of the enrollment.
  • A history of bronchial asthma, emphysema, heart block, angina, cardiomyopathy or myocardial infarction.
  • Any history or signs of congestive cardiac failure, or arrhythmia with a ventricular rate of less than 60 bpm.
  • Patients with severe mental or physical disorders which, in the opinion of the investigators, might affect responsiveness to therapy or any other aspect of the study.
  • Patients who are allergic to drugs with a chemical structure similar to labetalol or magnesium sulfate.
  • Patients given magnesium sulfate, labetalol or short acting beta blockers or calcium channel blockers less than 12 hours prior to enrollment in the study.
  • Evidence of fetal distress or fetal anomalies.
  • Inability to secure intravenous access.
  • Patient's primary physician declines to enroll patient in study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00293735

Locations
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77003
India
Institute of Maternal and Child Health Medicine
Kerala, India, 673008
Sponsors and Collaborators
Baylor College of Medicine
Investigators
Principal Investigator: Michael A Belfort, MD, PhD Baylor College of Medicine
  More Information

Publications:

Responsible Party: Michael Belfort, Chairman and Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT00293735     History of Changes
Other Study ID Numbers: H-28505
Study First Received: February 16, 2006
Last Updated: January 29, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Baylor College of Medicine:
Preeclampsia
Pregnancy
Hypertension
Eclampsia
HELLP Syndrome
Seizures
Prevention

Additional relevant MeSH terms:
Hypertension
Hypertension, Pregnancy-Induced
Pregnancy Complications
Eclampsia
Pre-Eclampsia
Vascular Diseases
Cardiovascular Diseases
Labetalol
Magnesium Sulfate
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic beta-Antagonists
Analgesics
Sensory System Agents
Central Nervous System Agents
Anesthetics
Central Nervous System Depressants
Anti-Arrhythmia Agents

ClinicalTrials.gov processed this record on April 16, 2014