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

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ClinicalTrials.gov Identifier: NCT01492608
Recruitment Status : Completed
First Posted : December 15, 2011
Last Update Posted : August 14, 2019
Sponsor:
Information provided by (Responsible Party):
Lene Huusom, Hvidovre University Hospital

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Cerebral Palsy Drug: Magnesium sulphate Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 560 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Administration of Antenatal Magnesium Sulphate for Prevention of Cerebral Palsy and Death in Preterm Infants (MASP-STUDY)
Actual Study Start Date : December 16, 2011
Actual Primary Completion Date : August 12, 2019
Actual Study Completion Date : August 12, 2019

Resource links provided by the National Library of Medicine


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 Name: 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 Name: Magnesium sulfat




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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)

  3. 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.

  4. 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.


Other Outcome Measures:
  1. 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).

  2. Resuscitation in delivery room [ Time Frame: First hour of life ]
    Mode of resuscitation in delivery room in the two groups (intervention and placebo group)

  3. Neonatal convulsions [ Time Frame: Assessed up to 18 months of age ]
    Clinically verified convulsions during first neonatal admission.

  4. 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.

  5. 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%


  6. Hypotension [ Time Frame: Assessed up to 18 months of age ]
    Need of volume therapy or vasopressors during first neonatal admission.

  7. 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.

  8. Retinopathy of prematurity [ Time Frame: At 18 months of age ]
    Retinopathy of prematurity stage 1-5

  9. Patent ductus arteriosus [ Time Frame: At 18 months of age ]
    Ultrasound verified patent ductus arteriosus

  10. Necrotizing enterocolitis [ Time Frame: Assessed up to 18 months of age ]
    Defined according to Bell's critiria

  11. Cerebral palsy [ Time Frame: At 18 months of age ]
    Mild (GMFCS level I), moderate (II-III), severe (IV-V), any

  12. Blood transfusion [ Time Frame: Assessed up to 18 months of age ]
    Number of children receiving bood transfusion during first admission

  13. Deafness [ Time Frame: At 18 months of age ]
    One or both ears



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01492608


Locations
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Denmark
Hanne Trap Wolf
Hvidovre, Danmark, Denmark, 2650
Gynækologisk afdeling D
Odense, Fyn, Denmark, 5000
Gynækologisk-Obstetrisk Afdeling
Aalborg, Jylland, Denmark, 9100
Gynækologisk-obstetrisk afdeling Y
Aarhus, Jylland, Denmark, 8200
Gynækologisk obstetrisk Afdeling
Esbjerg, Jylland, Denmark, 6700
Gynækologisk-obstetrisk afd.
Kolding, Jylland, Denmark, 6000
Gynækologisk obstetrisk afdeling
Randers, Jylland, Denmark, 8930
Gynækologisk-obstetrisk afd.
Silkeborg, Jylland, Denmark, 8600
Kvindeafdeling Y
Viborg, Jylland, Denmark, 8800
Obstetrisk Klinik
Copenhagen, Sjælland, Denmark, 2100
Gynækologisk Obstetrisk afdeling
Herlev, Sjælland, Denmark
Gynækologisk-Obstetrisk Afdeling
Hillerød, Sjælland, Denmark, 3400
Gynækologisk Obstetrisk afdeling
Holbæk, Sjælland, Denmark, 4300
Gynækologisk-obstetrisk afdeling
Næstved, Sjælland, Denmark, 4700
Sponsors and Collaborators
Hvidovre University Hospital
Investigators
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Principal Investigator: Lene Huusom, MD Department of Gynecology and Obstetrics, Hvidovre Hospital, Denmark
  Study Documents (Full-Text)

Documents provided by Lene Huusom, Hvidovre University Hospital:
Statistical Analysis Plan  [PDF] January 31, 2018


Publications:
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Responsible Party: Lene Huusom, Medical Doctor, Hvidovre University Hospital
ClinicalTrials.gov Identifier: NCT01492608     History of Changes
Other Study ID Numbers: EudraCT number 2011-000735-80
Projectnumber 2010-382 ( Registry Identifier: The Danish Committee on Biomedical Research Ethics )
First Posted: December 15, 2011    Key Record Dates
Last Update Posted: August 14, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Lene Huusom, Hvidovre University Hospital:
magnesium sulphate
preterm birth
cerebral palsy
Additional relevant MeSH terms:
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Cerebral Palsy
Nervous System Diseases
Brain Damage, Chronic
Brain Diseases
Central Nervous System Diseases
Magnesium Sulfate
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics
Central Nervous System Depressants
Anti-Arrhythmia Agents
Anticonvulsants
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Tocolytic Agents
Reproductive Control Agents