Labetalol Versus MgSO4 for the Prevention of Eclampsia Trial - Full Text View

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 II Phase III

MedlinePlus related topics:

High Blood Pressure Seizures

ChemIDplus related topics:

Labetalol Dilevalol Labetalol hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Open Label, Active Control, Parallel Assignment, Bio-equivalence Study

Official Title:	Labetalol Versus MgSO4 for the Prevention of Eclampsia Trial (LAMPET)

Further study details as provided by Utah HealthCare Institute:

Primary Outcome Measures:

Occurrence of eclamptic seizure(s) after enrollment in the study.

Secondary Outcome Measures:

Maternal: Blood pressure, pulse pressure and heart rate changes
Need for additional antihypertensive medication (defined by need to control BP > 160 mmHg systolic and/or 110 mmHg)
Subjective assessment of side effects by the patient
Objective assessment of new onset complications and/or side effects by the treating clinicians
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
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).
Fetal and Neonatal: Occurrence of newly diagnosed fetal distress during labor necessitating emergent delivery
Umbilical cord gases at delivery (if available in institution)
Apgar scores; and
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,
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.

Estimated Enrollment:	8000
Study Start Date:	May 2003
Estimated Study Completion Date:	December 2012
Estimated Primary Completion Date:	June 2012 (Final data collection date for primary outcome measure)

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

Contacts


Contact: Michael A Belfort, MD, PhD	801 743-4700	michael.belfort@HCAhealthcare.com

Contact: Janalee T Allred, RN, BSN	801-743-4709	janalee.thompson@HCAhealthcare.com

Locations


United States, Arizona
	St. Joseph's Regional Medical Center	Recruiting
	Phoenix, Arizona, United States, 85013
	Principal Investigator: James Balducci, MD

United States, California
	Loma Linda Medical Center	Recruiting
	Loma Linda, California, United States, 92354
	Principal Investigator: Bryan T. Oshiro, MD

United States, Kansas
	Overland Park Regional Medical Center	Recruiting
	Overland Park, Kansas, United States, 66215
	Principal Investigator: Tracey Cowles, MD
	Wesley Medical Center	Recruiting
	Wichita, Kansas, United States, 67214
	Principal Investigator: Margaret O'Hara, MD

United States, Louisiana
	Women's and Children's Hospital	Active, not recruiting
	Lafayette, Louisiana, United States, 70508

United States, Ohio
	The Toledo Hospital	Active, not recruiting
	Toledo, Ohio, United States, 43606

United States, Tennessee
	University of Tennessee	Recruiting
	Chattanooga, Tennessee, United States, 37403
	Principal Investigator: David C. Adair, MD
	University of Tennessee - Knoxville	Recruiting
	Knoxville, Tennessee, United States, 37996
	Principal Investigator: David C. Adair, MD

United States, Texas
	Medical City Hospital	Recruiting
	Dallas, Texas, United States, 75230
	Principal Investigator: Victor Vines, MD
	Woman's Hospital of Texas	Not yet recruiting
	Houston, Texas, United States, 77054
	Principal Investigator: Joanie Hare-Morris, MD

United States, Utah
	St. Mark's Hospital	Recruiting
	Salt Lake City, Utah, United States, 84124
	Principal Investigator: Michael A Belfort, MD, PhD
	University of Utah Medical Center	Recruiting
	Salt Lake City, Utah, United States, 84132
	Principal Investigator: Robert Silver, MD
	University of Utah Medical Center	Recruiting
	Salt Lake City, Utah, United States, 84132
	Contact: Jennifer Warren, MD 801-581-8425 jennifer.warren@hsc.utah.edu
	Principal Investigator: Robert Silver, MD

United States, Virginia
	Henrico Doctor's Hospital	Recruiting
	Richmond, Virginia, United States, 23294
	Principal Investigator: J.T. Christmas, MD

Germany
	Landstuhl Regional Medical Center	Recruiting
	Landstuhl, Germany
	Principal Investigator: Mark Sewell, MD

Sponsors and Collaborators

Utah HealthCare Institute

Investigators


Principal Investigator:	Michael A Belfort, MD, PhD	St. Mark's Hospital

More Information

Publications:

Belfort MA, Anthony J, Saade GR, Allen JC Jr; Nimodipine Study Group. A comparison of magnesium sulfate and nimodipine for the prevention of eclampsia. N Engl J Med. 2003 Jan 23;348(4):304-11.

Belfort MA. Is high cerebral perfusion pressure and cerebral flow predictive of impending seizures in preeclampsia? A case report. Hypertens Pregnancy. 2005;24(1):59-63.

Belfort MA, Tooke-Miller C, Allen JC Jr, Dizon-Townson D, Varner MA. Labetalol decreases cerebral perfusion pressure without negatively affecting cerebral blood flow in hypertensive gravidas. Hypertens Pregnancy. 2002;21(3):185-97.

Belfort MA, Tooke-Miller C, Varner M, Saade G, Grunewald C, Nisell H, Herd JA. Evaluation of a noninvasive transcranial Doppler and blood pressure-based method for the assessment of cerebral perfusion pressure in pregnant women. Hypertens Pregnancy. 2000;19(3):331-40. Erratum in: Hypertens Pregnancy 2001;20(1):139-40.

Riskin-Mashiah S, Belfort MA. Cerebrovascular hemodynamics in chronic hypertensive pregnant women who later develop superimposed preeclampsia. J Soc Gynecol Investig. 2005 Jan;12(1):28-32.

Belfort MA, Varner MW, Dizon-Townson DS, Grunewald C, Nisell H. Cerebral perfusion pressure, and not cerebral blood flow, may be the critical determinant of intracranial injury in preeclampsia: a new hypothesis. Am J Obstet Gynecol. 2002 Sep;187(3):626-34.

Belfort MA, Saade GR, Yared M, Grunewald C, Herd JA, Varner MA, Nisell H. Change in estimated cerebral perfusion pressure after treatment with nimodipine or magnesium sulfate in patients with preeclampsia. Am J Obstet Gynecol. 1999 Aug;181(2):402-7.

Responsible Party:	HCAPS ( Michael Belfort )
Study ID Numbers:	IND 63,966
First Received:	February 16, 2006
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00293735
Health Authority:	United States: Food and Drug Administration

Keywords provided by Utah HealthCare Institute:

Preeclampsia

Pregnancy

Hypertension

Eclampsia

HELLP Syndrome

Seizures

Prevention

Study placed in the following topic categories:

Labetalol

HELLP syndrome

HELLP Syndrome

Hypertension, Pregnancy-Induced

Pregnancy Complications

Eclampsia

Seizures

Vascular Diseases

Pregnancy toxemia /hypertension

Pre-Eclampsia

Preeclampsia

Hypertension

Additional relevant MeSH terms:

Neurotransmitter Agents

Sympatholytics

Adrenergic Agents

Molecular Mechanisms of Pharmacological Action

Physiological Effects of Drugs

Adrenergic alpha-Antagonists

Cardiovascular Agents

Antihypertensive Agents

Pharmacologic Actions

Autonomic Agents

Therapeutic Uses

Adrenergic beta-Antagonists

Cardiovascular Diseases

Adrenergic Antagonists

Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on September 05, 2008

Sponsored by:	Utah HealthCare Institute
Information provided by:	Utah HealthCare Institute
ClinicalTrials.gov Identifier:	NCT00293735