Beneficial Effects of Antenatal Magnesium Sulfate (BEAM Trial)

NCT ID: NCT00014989

Last Updated: 2019-07-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

2136 participants

Study Classification

INTERVENTIONAL

Study Start Date

1997-12-31

Study Completion Date

2007-06-30

Brief Summary

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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

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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.

Conditions

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Cerebral Palsy Intraventricular Hemorrhage Periventricular Leukomalacia Pulmonary Edema Abruptio Placentae

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Interventions

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magnesium sulfate

Intervention Type DRUG

Eligibility Criteria

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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
Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

The George Washington University Biostatistics Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Dwight Rouse, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Menachem Miodovnik

Role: STUDY_DIRECTOR

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Locations

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University of Alabama

Birmingham, Alabama, United States

Site Status

Dept of OB/GYN, University of Miami

Miami, Florida, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Dept of OB/GYN, Hutzel Hospital

Detroit, Michigan, United States

Site Status

St. Luke's - Roosevelt Hospital

New York, New York, United States

Site Status

University of North Carolina

Chapel Hill, North Carolina, United States

Site Status

Forsyth Memorial Hospital, Wake Forest University School of Medicine

Winston-Salem, North Carolina, United States

Site Status

The University Hospital, University of Cincinnati

Cincinnati, Ohio, United States

Site Status

Case Western University

Cleveland, Ohio, United States

Site Status

Dept of OB/GYN, Ohio State University

Columbus, Ohio, United States

Site Status

MCP Hahnemann University

Philadelphia, Pennsylvania, United States

Site Status

Dept of OB/GYN Magee Womens Hospital

Pittsburgh, Pennsylvania, United States

Site Status

Women and Infants Hospital

Providence, Rhode Island, United States

Site Status

Dept of OB/GYN, Southwestern Medical Center, University of Texas

Dallas, Texas, United States

Site Status

University of Texas Medical Branch - Galveston

Galveston, Texas, United States

Site Status

University of Texas - Houston

Houston, Texas, United States

Site Status

University of Utah Medical Center

Salt Lake City, Utah, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 7838646 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8946900 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8423946 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7761206 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7838643 (View on PubMed)

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.

Reference Type RESULT
PMID: 18753646 (View on PubMed)

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.

Reference Type RESULT
PMID: 19622997 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31143877 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26254839 (View on PubMed)

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.

Reference Type DERIVED
PMID: 20027029 (View on PubMed)

Related Links

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http://www.bsc.gwu.edu/mfmu/

Click here for more information on the NICHD MFMU Research Network.

Other Identifiers

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U10HD021414

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD021410

Identifier Type: NIH

Identifier Source: secondary_id

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U10HD027905

Identifier Type: NIH

Identifier Source: secondary_id

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U10HD027917

Identifier Type: NIH

Identifier Source: secondary_id

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U10HD027860

Identifier Type: NIH

Identifier Source: secondary_id

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U10HD027915

Identifier Type: NIH

Identifier Source: secondary_id

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U10HD034116

Identifier Type: NIH

Identifier Source: secondary_id

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U10HD034208

Identifier Type: NIH

Identifier Source: secondary_id

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U10HD034136

Identifier Type: NIH

Identifier Source: secondary_id

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U10HD027869

Identifier Type: NIH

Identifier Source: secondary_id

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U10HD036801

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD027861

Identifier Type: NIH

Identifier Source: secondary_id

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U10HD034122

Identifier Type: NIH

Identifier Source: secondary_id

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U10HD034210

Identifier Type: NIH

Identifier Source: secondary_id

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U10HD040500

Identifier Type: NIH

Identifier Source: secondary_id

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U10HD040485

Identifier Type: NIH

Identifier Source: secondary_id

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U10HD053097

Identifier Type: NIH

Identifier Source: secondary_id

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U10HD040544

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD040545

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD040560

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD040512

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NICHD-0800

Identifier Type: -

Identifier Source: org_study_id

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