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Labetalol Versus MgSO4 for the Prevention of Eclampsia Trial
This study is currently recruiting participants.
Verified by Utah HealthCare Institute, February 2009
First Received: February 16, 2006   Last Updated: February 17, 2009   History of Changes
Sponsored by: Utah HealthCare Institute
Information provided by: Utah HealthCare Institute
ClinicalTrials.gov Identifier: NCT00293735
  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

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)

Resource links provided by NLM:


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)
Arms Assigned Interventions
1. Labetolol: Active Comparator Drug: labetalol (seizure prevention)
2. Magnesium Sulfate: Sham Comparator Drug: MgSO4 (seizure prevention)

  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: Shalece Shalece, RN, MPH 801-743-4709 shalece.kofford@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, 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
Study First Received: February 16, 2006
Last Updated: February 17, 2009
ClinicalTrials.gov Identifier: NCT00293735     History of Changes
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:
Neurotransmitter Agents
Pregnancy Complications
Eclampsia
Adrenergic Agents
Seizures
Vascular Diseases
Pre-Eclampsia
Adrenergic alpha-Antagonists
Cardiovascular Agents
Antihypertensive Agents
Preeclampsia
Labetalol
HELLP Syndrome
Hypertension, Pregnancy-Induced
Adrenergic beta-Antagonists
Adrenergic Antagonists
Peripheral Nervous System Agents
Hypertension

Additional relevant MeSH terms:
Sympatholytics
Neurotransmitter Agents
Pregnancy Complications
Eclampsia
Adrenergic Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Vascular Diseases
Pre-Eclampsia
Adrenergic alpha-Antagonists
Cardiovascular Agents
Antihypertensive Agents
Pharmacologic Actions
Labetalol
Hypertension, Pregnancy-Induced
Autonomic Agents
Therapeutic Uses
Adrenergic beta-Antagonists
Cardiovascular Diseases
Adrenergic Antagonists
Peripheral Nervous System Agents
Hypertension

ClinicalTrials.gov processed this record on July 06, 2009