Magnesium Sulphate for Preterm Birth (MASP Study)

Sponsor

Hvidovre University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT01492608

Collaborator

(none)

560

Enrollment

Locations

Arms

91.9

Actual Duration (Months)

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

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.
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.
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 Design

Study Type:

Interventional

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 :

Dec 16, 2011

Actual Primary Completion Date :

Aug 12, 2019

Actual Study Completion Date :

Aug 12, 2019

Arms and Interventions

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

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

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

Other Names:

Magnesium sulfat

Outcome Measures

Primary Outcome Measures

Moderate or severe cerebral palsy [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

Perinatal death [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.
Composite outcome of outcome 1 and 2 (moderate-severe cerebral palsy and perinatal death) [At 18 months of age]
Frequency of the composite outcome in the two groups ((intervention and placebo group)
Blindness [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.
Apgar scores [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

Cranial ultrasound findings [Assessed up to 18 months of age]
Frequency of intraventricular hemorrhage and periventricular leukomalacia in the two groups ((intervention and placebo group).
Resuscitation in delivery room [First hour of life]
Mode of resuscitation in delivery room in the two groups (intervention and placebo group)
Neonatal convulsions [Assessed up to 18 months of age]
Clinically verified convulsions during first neonatal admission.
Use of respiratory support [Assessed up to 18 months of age]
Endotracheal ventilation or continuous positive airways pressure, or both during first neonatal admission.
Bronchopulmonary dysplasia (BPD) [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%
Hypotension [Assessed up to 18 months of age]
Need of volume therapy or vasopressors during first neonatal admission.
Length of neonatal hospitalization [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.
Retinopathy of prematurity [At 18 months of age]
Retinopathy of prematurity stage 1-5
Patent ductus arteriosus [At 18 months of age]
Ultrasound verified patent ductus arteriosus
Necrotizing enterocolitis [Assessed up to 18 months of age]
Defined according to Bell's critiria
Cerebral palsy [At 18 months of age]
Mild (GMFCS level I), moderate (II-III), severe (IV-V), any
Blood transfusion [Assessed up to 18 months of age]
Number of children receiving bood transfusion during first admission
Deafness [At 18 months of age]
One or both ears

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hanne Trap Wolf	Hvidovre	Danmark	Denmark	2650
2	Gynækologisk afdeling D	Odense	Fyn	Denmark	5000
3	Gynækologisk-Obstetrisk Afdeling	Aalborg	Jylland	Denmark	9100
4	Gynækologisk-obstetrisk afdeling Y	Aarhus	Jylland	Denmark	8200
5	Gynækologisk obstetrisk Afdeling	Esbjerg	Jylland	Denmark	6700
6	Gynækologisk-obstetrisk afd.	Kolding	Jylland	Denmark	6000
7	Gynækologisk obstetrisk afdeling	Randers	Jylland	Denmark	8930
8	Gynækologisk-obstetrisk afd.	Silkeborg	Jylland	Denmark	8600
9	Kvindeafdeling Y	Viborg	Jylland	Denmark	8800
10	Obstetrisk Klinik	Copenhagen	Sjælland	Denmark	2100
11	Gynækologisk Obstetrisk afdeling	Herlev	Sjælland	Denmark
12	Gynækologisk-Obstetrisk Afdeling	Hillerød	Sjælland	Denmark	3400
13	Gynækologisk Obstetrisk afdeling	Holbæk	Sjælland	Denmark	4300
14	Gynækologisk-obstetrisk afdeling	Næstved	Sjælland	Denmark	4700