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CompletedNCT00014989BEAMUpdated Jul 12, 2019

Beneficial Effects of Antenatal Magnesium Sulfate (BEAM Trial)

A Phase 3 interventional study of magnesium sulfate in Cerebral Palsy, Intraventricular Hemorrhage and Periventricular Leukomalacia, sponsored by The George Washington University Biostatistics Center. Completed at 17 sites in United States. Open to female participants. Per ClinicalTrials.gov, last updated 2019-07-12.

Sponsored by The George Washington University Biostatistics Center · Phase 3, Interventional, and Prevention

Phase
Phase 3
Study type
Interventional
Enrollment
2,136
Allocation
Randomized
Sex
Female
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Study 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.

Read the 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.

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Conditions studied

  • Cerebral Palsy
  • Intraventricular Hemorrhage
  • Periventricular Leukomalacia
  • Pulmonary Edema
  • Abruptio Placentae

Keywords

  • Preterm delivery
  • Cerebral palsy
  • Magnesium sulfate
03

Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
Female
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Single group
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
2,136 participants (actual)

Interventions

  • Drugmagnesium sulfate
05

What researchers measure

Primary outcomes

  1. Composite outcome of death or moderate to severe cerebral palsy

Secondary outcomes

  1. Maternal

  2. Chorioamnionitis

  3. Endometritis

  4. Other infectious morbidity

  5. Pulmonary edema

  6. Placental abruption

  7. Neonatal

  8. Stillbirth and neonatal death

  9. Intraventricular hemorrhage

  10. Neonatal infectious morbidity

  11. Neonatal noninfectious morbidity

  12. Birth weight

  13. Days in NICU

06

Study locations

17 sites
  • University of Alabama
    Birmingham, Alabama 35233, United States
  • Dept of OB/GYN, University of Miami
    Miami, Florida 33136, United States
  • Northwestern University
    Chicago, Illinois 60611, United States
  • Dept of OB/GYN, Hutzel Hospital
    Detroit, Michigan 48201, United States
  • St. Luke's - Roosevelt Hospital
    New York, New York 10019, United States
  • University of North Carolina
    Chapel Hill, North Carolina 27599, United States
  • Forsyth Memorial Hospital, Wake Forest University School of Medicine
    Winston-Salem, North Carolina 27103, United States
  • The University Hospital, University of Cincinnati
    Cincinnati, Ohio 45267-0794, United States
  • Case Western University
    Cleveland, Ohio 44109, United States
  • Dept of OB/GYN, Ohio State University
    Columbus, Ohio 43210, United States
  • MCP Hahnemann University
    Philadelphia, Pennsylvania 19102, United States
  • Dept of OB/GYN Magee Womens Hospital
    Pittsburgh, Pennsylvania 15213, United States
  • Women and Infants Hospital
    Providence, Rhode Island 02905-2499, United States
  • Dept of OB/GYN, Southwestern Medical Center, University of Texas
    Dallas, Texas 75235-9032, United States
  • University of Texas Medical Branch - Galveston
    Galveston, Texas 77555, United States
  • University of Texas - Houston
    Houston, Texas 77030, United States
  • University of Utah Medical Center
    Salt Lake City, Utah 84132, United States
07

References and documents

Publications

  • 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. PubMed 7838646 ↗
  • 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. PubMed 8946900 ↗
  • 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. PubMed 8423946 ↗
  • 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. PubMed 7761206 ↗
  • 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. Erratum In: Pediatrics 2001 Aug;108(2):238. PubMed 7838643 ↗
  • 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. PubMed 18753646 ↗
  • 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. PubMed 19622997 ↗
  • 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. PubMed 31143877 ↗
  • 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. PubMed 26254839 ↗
  • 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. PubMed 20027029 ↗

Individual participant data

Plan to share: Yes — The data will be shared after completion and publication of the main analyses in accordance with NIH policy. The dataset can be obtained by email at mfmudatasets@bsc.gwu.edu.

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Registry details

Key details

Study ID
NCT00014989
Lead sponsor
The George Washington University Biostatistics Center
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Responsible party
Sponsor
First posted
Apr 18, 2001
Start date
Dec 1997
Primary completion
Feb 2007
Completion
Jun 2007
Last update
Jul 12, 2019

Study contacts

Dwight Rouse, MD
principal investigator · University of Alabama at Birmingham
Menachem Miodovnik
study director · Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jul 2019. You cannot join it, but the record below documents what was studied.

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