Clinical trial NCT00014989: Beneficial Effects of Antenatal Magnesium Sulfate (BEAM Trial)
Official title: Randomized Clinical Trial of the Beneficial Effects of Antenatal Magnesium Sulfate (BEAM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cerebral Palsy
Intraventricular Hemorrhage
Periventricular Leukomalacia
Pulmonary Edema
Abruptio Placentae
Keywords: Preterm delivery
Cerebral palsy
Magnesium sulfate
Lead sponsor: The George Washington University Biostatistics Center
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2001-04-18
Enrollment: 2136
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: As many more premature infants survive, the numbers of these infants with health problems increases. The rate of cerebral palsy (CP) in extremely premature infants is approximately 20%. Magnesium sulfate, the most commonly used drug in the US to stop premature labor, may prevent CP. This trial tests whether magnesium sulfate given to a woman in labor with a premature fetus (24 to 31 weeks out of 40) will reduce the rate of death or moderate to severe CP in the children at 2 years. The children receive ultrasounds of their brains as infants and attend three follow-up visits over two years to assess their health and development.

Detailed description: The prevalence of cerebral palsy is increasing as the survival rate of extremely premature infants is improving. Studies have suggested an apparent association between maternal magnesium sulfate administration and a reduced risk of cerebral palsy. Other studies have suggested a possible association between magnesium sulfate and a reduction in neonatal cranial ultrasound abnormalities which may be markers for subsequent development of cerebral palsy.

This multicenter trial tests whether prophylactic magnesium sulfate given to women, for whom preterm delivery is imminent, reduces the risk of death or moderate to severe cerebral palsy in their children. Women presenting from 24.0 to 31.6 weeks gestation with advanced preterm labor or premature rupture of the membranes (pPROM) and no recent exposure to magnesium sulfate are randomized to receive either intravenous magnesium sulfate or masked study drug placebo. The study drug is administered as a 6 gram loading dose followed by a 2 gram/hour infusion (or equivalent rate for placebo). If after 12 hours, delivery has not occurred and is not anticipated, the infusion is stopped. No other parenteral tocolytics other than the IV medication may be used. Retreatment with study medication is given any time labor recurs or delivery is anticipated until gestational age is \> 34.0 wks. Standard clinical management and therapy is to be maintained for all study patients. Patients are assessed for signs of intolerance to the study medications and maternal data are collected up to hospital discharge. A sample of venous blood is collected and neonatal cranial ultrasounds are performed. Up to three follow-up visits are scheduled over two years where certified examiners, masked to study group assignment, collect physical and neurological data, including a modified Gross Motor Function Classification Scale. The Bayley Scales of Infant Development is also administered. Cranial ultrasounds are reviewed centrally.

The primary outcome is a composite outcome of death or moderate to severe cerebral palsy. Secondary outcomes include maternal infectious morbidity, pulmonary edema and placental abruption, neonatal stillbirth and death, intraventricular hemorrhage, periventricular leukomalacia, neonatal infectious and noninfectious morbidity.

Eligibility criteria: Inclusion Criteria:

* Pregnant with diagnosis of preterm labor
* Membrane rupture or delivery definitely planned within 24 hours
* Gestational age \> 24.0 and \< 31.6 wks, viable fetus

Exclusion Criteria:

* Prior IV magnesium sulfate therapy within 12 hours of screening
* Delivery expected \<2 hrs
* Cervical dilation \> 8 cm
* More than 2 fetuses
* Known major fetal anomalies
* Hypertension or preeclampsia
* Maternal medical complications contraindicating magnesium sulfate treatment
* Participation in any intervention study which influences infant neurological outcome
* Previous participation in this trial

Primary outcomes:
measure: Composite outcome of death or moderate to severe cerebral palsy
Secondary outcomes:
measure: Maternal
measure: Chorioamnionitis
measure: Endometritis
measure: Other infectious morbidity
measure: Pulmonary edema
measure: Placental abruption
measure: Neonatal
measure: Stillbirth and neonatal death
measure: Intraventricular hemorrhage
measure: Neonatal infectious morbidity
measure: Neonatal noninfectious morbidity
measure: Birth weight
measure: Days in NICU
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Miami
country: United States
facility: Dept of OB/GYN, University of Miami
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Detroit
country: United States
facility: Dept of OB/GYN, Hutzel Hospital
state: Michigan
city: New York
country: United States
facility: St. Luke's - Roosevelt Hospital
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Winston-Salem
country: United States
facility: Forsyth Memorial Hospital, Wake Forest University School of Medicine
state: North Carolina
city: Cincinnati
country: United States
facility: The University Hospital, University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Case Western University
state: Ohio
city: Columbus
country: United States
facility: Dept of OB/GYN, Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: MCP Hahnemann University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Dept of OB/GYN Magee Womens Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Women and Infants Hospital
state: Rhode Island
city: Dallas
country: United States
facility: Dept of OB/GYN, Southwestern Medical Center, University of Texas
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical Branch - Galveston
state: Texas
city: Houston
country: United States
facility: University of Texas - Houston
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Medical Center
state: Utah
Study officials:
affiliation: University of Alabama at Birmingham
name: Dwight Rouse, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: Menachem Miodovnik
role: STUDY_DIRECTOR
References:
citation: Nelson KB, Grether JK. Can magnesium sulfate reduce the risk of cerebral palsy in very low birthweight infants? Pediatrics. 1995 Feb;95(2):263-9.
citation: Schendel DE, Berg CJ, Yeargin-Allsopp M, Boyle CA, Decoufle P. Prenatal magnesium sulfate exposure and the risk for cerebral palsy or mental retardation among very low-birth-weight children aged 3 to 5 years. JAMA. 1996 Dec 11;276(22):1805-10.
citation: Hallak M, Berry SM, Madincea F, Romero R, Evans MI, Cotton DB. Fetal serum and amniotic fluid magnesium concentrations with maternal treatment. Obstet Gynecol. 1993 Feb;81(2):185-8.
citation: Aziz K, Vickar DB, Sauve RS, Etches PC, Pain KS, Robertson CM. Province-based study of neurologic disability of children weighing 500 through 1249 grams at birth in relation to neonatal cerebral ultrasound findings. Pediatrics. 1995 Jun;95(6):837-44.
citation: Pinto-Martin JA, Riolo S, Cnaan A, Holzman C, Susser MW, Paneth N. Cranial ultrasound prediction of disabling and nondisabling cerebral palsy at age two in a low birth weight population. Pediatrics. 1995 Feb;95(2):249-54.
citation: Rouse DJ, Hirtz DG, Thom E, Varner MW, Spong CY, Mercer BM, Iams JD, Wapner RJ, Sorokin Y, Alexander JM, Harper M, Thorp JM Jr, Ramin SM, Malone FD, Carpenter M, Miodovnik M, Moawad A, O'Sullivan MJ, Peaceman AM, Hankins GD, Langer O, Caritis SN, Roberts JM; Eunice Kennedy Shriver NICHD Maternal-Fetal Medicine Units Network. A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy. N Engl J Med. 2008 Aug 28;359(9):895-905. doi: 10.1056/NEJMoa0801187.
citation: Costantine MM, Weiner SJ; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units Network (MFMU). Effects of antenatal exposure to magnesium sulfate on neuroprotection and mortality in preterm infants: a meta-analysis. Obstet Gynecol. 2009 Aug;114(2 Pt 1):354-364. doi: 10.1097/AOG.0b013e3181ae98c2.
citation: Buhimschi CS, Jablonski KA, Rouse DJ, Varner MW, Reddy UM, Mercer BM, Leveno KJ, Wapner RJ, Sorokin Y, Thorp JM Jr, Ramin SM, Malone FD, Carpenter MW, O'Sullivan MJ, Peaceman AM, Saade GR, Dudley D, Caritis SN, Buhimschi IA; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Cord Blood Haptoglobin, Cerebral Palsy and Death in Infants of Women at Risk for Preterm Birth: A Secondary Analysis of a Randomised Controlled Trial. EClinicalMedicine. 2019 Mar 22;9:11-18. doi: 10.1016/j.eclinm.2019.03.009. eCollection 2019 Mar.
citation: Hirtz DG, Weiner SJ, Bulas D, DiPietro M, Seibert J, Rouse DJ, Mercer BM, Varner MW, Reddy UM, Iams JD, Wapner RJ, Sorokin Y, Thorp JM Jr, Ramin SM, Malone FD, Carpenter MW, O'Sullivan MJ, Peaceman AM, Hankins GD, Dudley D, Caritis SN; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Antenatal Magnesium and Cerebral Palsy in Preterm Infants. J Pediatr. 2015 Oct;167(4):834-839.e3. doi: 10.1016/j.jpeds.2015.06.067. Epub 2015 Aug 5.
citation: Twickler DM, McIntire DD, Alexander JM, Leveno KJ. Effects of magnesium sulfate on preterm fetal cerebral blood flow using Doppler analysis: a randomized controlled trial. Obstet Gynecol. 2010 Jan;115(1):21-25. doi: 10.1097/AOG.0b013e3181c4f7c1.