Magnesium Sulphate for Preterm Birth (MASP Study) (MASP)

August 13, 2019 updated by: Lene Huusom, Hvidovre University Hospital

Administration of Antenatal Magnesium Sulphate for Prevention of Cerebral Palsy and Death in Preterm Infants (MASP-STUDY)

The purpose of the study is to assess whether magnesium sulphate for women at risk of preterm birth can protect their children against cerebral palsy. The results from this randomised controlled trial will be added to the previous meta-analysis to obtain firm evidence for magnesium sulphate as a neuroprotector, and determine whether it should be used as standard therapy for women in preterm birth.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Cerebral palsy consists of chronic and non-progressive clinical syndromes that are characterized by motor and postural dysfunction. In affected infants, voluntary movements become difficult and limited, and although clinical expression may change with time, this disability is accompanied with major personal and socioeconomic burdens. Preterm infants have increased risk of cerebral palsy, which is inversely correlated with gestational age at birth.

Previous studies have indicated that magnesium sulphate may be neuroprotective for the preterm infant, when the drug is given to women prior to preterm birth.

However, this benefit of antenatal magnesium sulphate was recently questioned by Trial Sequential Analysis (TSA), a statistical method that adjusts for risk of random error on published meta-analyses. TSA demonstrates that additional data are needed before accepting magnesium sulphate as evidence based therapy for women in preterm labour. Therefore we will close the gap by performing a new randomised clinical trial (RCT), which aims to assess whether magnesium sulphate for women prior to preterm birth can protect their children against cerebral palsy.

The RCT will not individually have the power to detect a significant difference between magnesium and placebo. Instead, when the trial is completed, the results will be added to the previous meta-analysis to obtain firm evidence for magnesium sulphate as a neuroprotector, and determine whether it should be used as standard therapy for women in preterm birth.

From Denmark 560 eligible women, who are at risk of preterm birth at 24 to 32 weeks of gestation, will be randomised to receive either intravenous magnesium sulphate or placebo. Randomisation will be performed blinded by computer generated random numbers.

The children are followed up by medical records and by Ages and Stages Questionnaire (ASQ) in the age of 18 month or older. To screen for cerebral palsy, the domains gross motor skills and fine motor skills are together with the total score the most suitable measures.

  1. If the medical record is without any information on cerebral palsy and/or delayed motor development or if there is no medical record to be found and there is an ASQ score above the 20% percentile (in the domains of gross motor function, fine motor function or total score), the child is classified as not having cerebral palsy.
  2. If the child in the ASQ scores under the 20% percentile in the domains of gross motor function, fine motor function and/or total score and there is no diagnosis of cerebral palsy in the medical record, the parents are contacted. The parents are contacted as well, if there is no medical record to be found. If the parents explain that the child is developing normally and is not seen by doctors or physiotherapists, the child is classified as not having cerebral palsy. If the parents state that the child is not developing normally, the child is invited to further examination by a pediatric neurologist.
  3. If the child is diagnosed with cerebral palsy or delayed motor development, the medical journal is reviewed by a pediatric neurologist to verify the diagnosis. If there is any doubt about the correctness of the diagnosis, the child is invited to further examination by a pediatric neurologist.

Study Type

Interventional

Enrollment (Actual)

560

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
    • Danmark
      • Hvidovre, Danmark, Denmark, 2650
        • Hanne Trap Wolf
    • Fyn
      • Odense, Fyn, Denmark, 5000
        • Gynækologisk afdeling D
    • Jylland
      • Aalborg, Jylland, Denmark, 9100
        • Gynækologisk-obstetrisk afdeling
      • Aarhus, Jylland, Denmark, 8200
        • Gynækologisk-obstetrisk afdeling Y
      • Esbjerg, Jylland, Denmark, 6700
        • Gynækologisk obstetrisk afdeling
      • Kolding, Jylland, Denmark, 6000
        • Gynækologisk-obstetrisk afd.
      • Randers, Jylland, Denmark, 8930
        • Gynækologisk obstetrisk afdeling
      • Silkeborg, Jylland, Denmark, 8600
        • Gynækologisk-obstetrisk afd.
      • Viborg, Jylland, Denmark, 8800
        • Kvindeafdeling Y
    • Sjælland
      • Copenhagen, Sjælland, Denmark, 2100
        • Obstetrisk Klinik
      • Herlev, Sjælland, Denmark
        • Gynækologisk obstetrisk afdeling
      • Hillerød, Sjælland, Denmark, 3400
        • Gynækologisk-obstetrisk afdeling
      • Holbæk, Sjælland, Denmark, 4300
        • Gynækologisk obstetrisk afdeling
      • Næstved, Sjælland, Denmark, 4700
        • Gynækologisk-obstetrisk afdeling

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Gestational age 24+0-31+6 weeks
  • Singletons or twins
  • Preterm rupture of membranes at 24+0-31+6 weeks with contractions and expected birth within 2-24 hours
  • Preterm contractions and expected birth within 2-24 hours
  • Anticipated delivery within 2-24 hours of other reasons (due to for example fetal growth restriction)
  • Age 18 years at inclusion

Exclusion Criteria:

  • Major fetal abnormalities or fetal death. (Major fetal abnormalities are chromosome abnormalities, myelomeningocele and cerebral abnormalities that gives neurological handicaps)
  • Maternal contraindication to magnesium sulphate (for example pulmonary disorders, kidney diseases with creatinin > 100, myasthenia gravis, atrioventricular block, treatment with aminoglycosides)
  • Magnesium sulphate given for other reasons (for example for prevention of eclampsia)
  • Patients who do not speak and understand Danish
  • Allergies towards magnesium sulphate

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Magnesium sulphate
Magnesium sulphate will be given as a loading dose of 5 g infused for 20-30 minutes, followed by a maintenance dose of 1 g per hour. Placebo will be given in identical appearing doses. The maintenance infusion will be continued until delivery appears, or for 24 hours if delivery does not occur or no longer is considered imminent. The infusion will be resumed when delivery is considered imminent again. Another loading dose of 5 g will be given if at least 6 hours has passed after infusion was stopped. The doses that are used in this project are similar to those used for prevention of eclampsia among women with severe preeclampsia.
Drug: Magnesium sulphate
Magnesium sulphate will be given as a loading dose of 5 g infused for 20-30 minutes, followed by a maintenance dose of 1 g per hour. Placebo will be given in identical appearing doses. The maintenance infusion will be continued until delivery appears, or for 24 hours if delivery does not occur or no longer is considered imminent. The infusion will be resumed when delivery is considered imminent again. Another loading dose of 5 g will be given if at least 6 hours has passed after infusion was stopped. The doses that are used in this project are similar to those used for prevention of eclampsia among women with severe preeclampsia.
Other Names:
  • Magnesium sulfat
Placebo Comparator: Natriumchlorid
Placebo and the active drug (Magnesium sulphate) will be administered identically (same loading and maintenance dose for the same period of time).
Drug: Magnesium sulphate
Magnesium sulphate will be given as a loading dose of 5 g infused for 20-30 minutes, followed by a maintenance dose of 1 g per hour. Placebo will be given in identical appearing doses. The maintenance infusion will be continued until delivery appears, or for 24 hours if delivery does not occur or no longer is considered imminent. The infusion will be resumed when delivery is considered imminent again. Another loading dose of 5 g will be given if at least 6 hours has passed after infusion was stopped. The doses that are used in this project are similar to those used for prevention of eclampsia among women with severe preeclampsia.
Other Names:
  • Magnesium sulfat

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Moderate or severe cerebral palsy
Time Frame: At 18 months of age
The difference in the number of children with moderate or severe cerebral palsy at 18 months of age, whose mothers had magnesium sulphate before birth compared to the group of children whose mothers received placebo before birth.
At 18 months of age

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Perinatal death
Time Frame: From date of randomization until the date of death from any cause, assessed up to 18 months
The difference in the number of children with perinatal death, whose mothers had magnesium sulphate before birth compared to the group of children whose mothers received placebo before birth.
From date of randomization until the date of death from any cause, assessed up to 18 months
Composite outcome of outcome 1 and 2 (moderate-severe cerebral palsy and perinatal death)
Time Frame: At 18 months of age
Frequency of the composite outcome in the two groups ((intervention and placebo group)
At 18 months of age
Blindness
Time Frame: At 18 months of age
The difference in the number of children with blindness at 18 months of age, whose mothers had magnesium sulphate before birth compared to the group of children whose mothers received placebo before birth.
At 18 months of age
Apgar scores
Time Frame: At 1 minute and 5 minutes after birth
The difference in apgar scores in the group of children, whose mothers had magnesium sulphate before birth compared to the group of children whose mothers received placebo before birth.
At 1 minute and 5 minutes after birth

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cranial ultrasound findings
Time Frame: Assessed up to 18 months of age
Frequency of intraventricular hemorrhage and periventricular leukomalacia in the two groups ((intervention and placebo group).
Assessed up to 18 months of age
Resuscitation in delivery room
Time Frame: First hour of life
Mode of resuscitation in delivery room in the two groups (intervention and placebo group)
First hour of life
Neonatal convulsions
Time Frame: Assessed up to 18 months of age
Clinically verified convulsions during first neonatal admission.
Assessed up to 18 months of age
Use of respiratory support
Time Frame: Assessed up to 18 months of age
Endotracheal ventilation or continuous positive airways pressure, or both during first neonatal admission.
Assessed up to 18 months of age
Bronchopulmonary dysplasia (BPD)
Time Frame: Assessed up to 18 months of age

Mild BPD: Need for continuous, supplemental oxygen at ≥ 28 days but not at 36-week postmenstrual age.

Moderate BPD: Need for continuous, supplemental oxygen at 28 days, in addition to supplemental oxygen at ≤30% at 36-week postmenstrual age.

Severe BPD: Need for continuous, supplemental oxygen at 28 days and, at 36-week postmenstrual age, the need for mechanical ventilation and/or oxygen >30%
Assessed up to 18 months of age
Hypotension
Time Frame: Assessed up to 18 months of age
Need of volume therapy or vasopressors during first neonatal admission.
Assessed up to 18 months of age
Length of neonatal hospitalization
Time Frame: Assessed up to 18 months of age
Length of the neonatal hospitalization measured in days. From time of birth to discharge after first neonatal admisson or until death.
Assessed up to 18 months of age
Retinopathy of prematurity
Time Frame: At 18 months of age
Retinopathy of prematurity stage 1-5
At 18 months of age
Patent ductus arteriosus
Time Frame: At 18 months of age
Ultrasound verified patent ductus arteriosus
At 18 months of age
Necrotizing enterocolitis
Time Frame: Assessed up to 18 months of age
Defined according to Bell's critiria
Assessed up to 18 months of age
Cerebral palsy
Time Frame: At 18 months of age
Mild (GMFCS level I), moderate (II-III), severe (IV-V), any
At 18 months of age
Blood transfusion
Time Frame: Assessed up to 18 months of age
Number of children receiving bood transfusion during first admission
Assessed up to 18 months of age
Deafness
Time Frame: At 18 months of age
One or both ears
At 18 months of age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hvidovre University Hospital

Investigators

  • Principal Investigator: Lene Huusom, MD, Department of Gynecology and Obstetrics, Hvidovre Hospital, Denmark

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 16, 2011

Primary Completion (Actual)

August 12, 2019

Study Completion (Actual)

August 12, 2019

Study Registration Dates

First Submitted

December 11, 2011

First Submitted That Met QC Criteria

December 14, 2011

First Posted (Estimate)

December 15, 2011

Study Record Updates

Last Update Posted (Actual)

August 14, 2019

Last Update Submitted That Met QC Criteria

August 13, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EudraCT number 2011-000735-80
  • Projectnumber 2010-382 (Registry Identifier: The Danish Committee on Biomedical Research Ethics)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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