Magnesium Sulphate for Preterm Birth (MASP Study)

NCT ID: NCT01492608

Last Updated: 2019-08-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 560 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-12-16
• Study Completion Date: 2019-08-12

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.

Conditions

Cerebral Palsy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Magnesium sulphate

Intervention Type: DRUG

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.

Natriumchlorid

Placebo and the active drug (Magnesium sulphate) will be administered identically (same loading and maintenance dose for the same period of time).

Group Type: PLACEBO_COMPARATOR

Magnesium sulphate

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Magnesium sulfat

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Hvidovre University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Lene Huusom

Medical Doctor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lene Huusom, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Gynecology and Obstetrics, Hvidovre Hospital, Denmark

Locations

Hanne Trap Wolf

Hvidovre, Danmark, Denmark

Gynækologisk afdeling D

Odense, Fyn, Denmark

Gynækologisk-Obstetrisk Afdeling

Aalborg, Jylland, Denmark

Gynækologisk-obstetrisk afdeling Y

Aarhus, Jylland, Denmark

Gynækologisk obstetrisk Afdeling

Esbjerg, Jylland, Denmark

Gynækologisk-obstetrisk afd.

Kolding, Jylland, Denmark

Gynækologisk obstetrisk afdeling

Randers, Jylland, Denmark

Gynækologisk-obstetrisk afd.

Silkeborg, Jylland, Denmark

Kvindeafdeling Y

Viborg, Jylland, Denmark

Obstetrisk Klinik

Copenhagen, Region Sjælland, Denmark

Gynækologisk Obstetrisk afdeling

Herlev, Region Sjælland, Denmark

Gynækologisk-Obstetrisk Afdeling

Hillerød, Region Sjælland, Denmark

Gynækologisk Obstetrisk afdeling

Holbæk, Region Sjælland, Denmark

Gynækologisk-obstetrisk afdeling

Næstved, Region Sjælland, Denmark

Countries

Denmark

References

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.

Reference Type: BACKGROUND

PMID: 21197681 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

Projectnumber 2010-382

Identifier Type: REGISTRY

Identifier Source: secondary_id

EudraCT number 2011-000735-80

Identifier Type: -

Identifier Source: org_study_id