Clinical trial NCT01492608: Magnesium Sulphate for Preterm Birth (MASP Study)
Official title: Administration of Antenatal Magnesium Sulphate for Prevention of Cerebral Palsy and Death in Preterm Infants (MASP-STUDY)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cerebral Palsy
Keywords: magnesium sulphate
preterm birth
cerebral palsy
Lead sponsor: Hvidovre University Hospital
Sponsor class: OTHER
First posted: 2011-12-15
Enrollment: 560
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Eligibility 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

Primary outcomes:
measure: Moderate or severe cerebral palsy
timeFrame: At 18 months of age
Secondary outcomes:
measure: Perinatal death
timeFrame: From date of randomization until the date of death from any cause, assessed up to 18 months
measure: Composite outcome of outcome 1 and 2 (moderate-severe cerebral palsy and perinatal death)
timeFrame: At 18 months of age
measure: Blindness
timeFrame: At 18 months of age
measure: Apgar scores
timeFrame: At 1 minute and 5 minutes after birth
Other outcomes:
measure: Cranial ultrasound findings
timeFrame: Assessed up to 18 months of age
measure: Resuscitation in delivery room
timeFrame: First hour of life
measure: Neonatal convulsions
timeFrame: Assessed up to 18 months of age
measure: Use of respiratory support
timeFrame: Assessed up to 18 months of age
measure: Bronchopulmonary dysplasia (BPD)
timeFrame: Assessed up to 18 months of age
measure: Hypotension
timeFrame: Assessed up to 18 months of age
measure: Length of neonatal hospitalization
timeFrame: Assessed up to 18 months of age
measure: Retinopathy of prematurity
timeFrame: At 18 months of age
measure: Patent ductus arteriosus
timeFrame: At 18 months of age
measure: Necrotizing enterocolitis
timeFrame: Assessed up to 18 months of age
measure: Cerebral palsy
timeFrame: At 18 months of age
measure: Blood transfusion
timeFrame: Assessed up to 18 months of age
measure: Deafness
timeFrame: At 18 months of age
Locations:
city: Hvidovre
country: Denmark
facility: Hanne Trap Wolf
state: Danmark
city: Odense
country: Denmark
facility: Gynækologisk afdeling D
state: Fyn
city: Aalborg
country: Denmark
facility: Gynækologisk-Obstetrisk Afdeling
state: Jylland
city: Aarhus
country: Denmark
facility: Gynækologisk-obstetrisk afdeling Y
state: Jylland
city: Esbjerg
country: Denmark
facility: Gynækologisk obstetrisk Afdeling
state: Jylland
city: Kolding
country: Denmark
facility: Gynækologisk-obstetrisk afd.
state: Jylland
city: Randers
country: Denmark
facility: Gynækologisk obstetrisk afdeling
state: Jylland
city: Silkeborg
country: Denmark
facility: Gynækologisk-obstetrisk afd.
state: Jylland
city: Viborg
country: Denmark
facility: Kvindeafdeling Y
state: Jylland
city: Copenhagen
country: Denmark
facility: Obstetrisk Klinik
state: Sjælland
city: Herlev
country: Denmark
facility: Gynækologisk Obstetrisk afdeling
state: Sjælland
city: Hillerød
country: Denmark
facility: Gynækologisk-Obstetrisk Afdeling
state: Sjælland
city: Holbæk
country: Denmark
facility: Gynækologisk Obstetrisk afdeling
state: Sjælland
city: Næstved
country: Denmark
facility: Gynækologisk-obstetrisk afdeling
state: Sjælland
Study officials:
affiliation: Department of Gynecology and Obstetrics, Hvidovre Hospital, Denmark
name: Lene Huusom, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Huusom LD, Secher NJ, Pryds O, Whitfield K, Gluud C, Brok J. Antenatal magnesium sulphate may prevent cerebral palsy in preterm infants--but are we convinced? Evaluation of an apparently conclusive meta-analysis with trial sequential analysis. BJOG. 2011 Jan;118(1):1-5. doi: 10.1111/j.1471-0528.2010.02782.x. No abstract available.