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| ID | Type | Description | Link |
|---|---|---|---|
| Projectnumber 2010-382 | Registry Identifier | The Danish Committee on Biomedical Research Ethics |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Magnesium sulphate | Active Comparator | 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 Comparator | Placebo and the active drug (Magnesium sulphate) will be administered identically (same loading and maintenance dose for the same period of time). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Magnesium sulphate | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Moderate or severe cerebral palsy | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Perinatal death | 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Cranial ultrasound findings | 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 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Lene Huusom, MD | Department of Gynecology and Obstetrics, Hvidovre Hospital, Denmark | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hanne Trap Wolf | Hvidovre | Danmark | 2650 | Denmark | ||
| Gynækologisk afdeling D |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21197681 | Background | 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. |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 31, 2018 | Jan 6, 2019 | SAP_000.pdf |
| ID | Term |
|---|---|
| D002547 | Cerebral Palsy |
| D047928 | Premature Birth |
| ID | Term |
|---|---|
| D001925 | Brain Damage, Chronic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D008278 | Magnesium Sulfate |
| ID | Term |
|---|---|
| D017616 | Magnesium Compounds |
| D007287 | Inorganic Chemicals |
| D013431 | Sulfates |
| D013464 | Sulfuric Acids |
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|
Frequency of the composite outcome in the two groups ((intervention and placebo group) |
| At 18 months of age |
| Blindness | 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 | 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 |
Mode of resuscitation in delivery room in the two groups (intervention and placebo group)
| First hour of life |
| Neonatal convulsions | Clinically verified convulsions during first neonatal admission. | Assessed up to 18 months of age |
| Use of respiratory support | Endotracheal ventilation or continuous positive airways pressure, or both during first neonatal admission. | Assessed up to 18 months of age |
| Bronchopulmonary dysplasia (BPD) | 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 | Need of volume therapy or vasopressors during first neonatal admission. | Assessed up to 18 months of age |
| Length of neonatal hospitalization | 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 | Retinopathy of prematurity stage 1-5 | At 18 months of age |
| Patent ductus arteriosus | Ultrasound verified patent ductus arteriosus | At 18 months of age |
| Necrotizing enterocolitis | Defined according to Bell's critiria | Assessed up to 18 months of age |
| Cerebral palsy | Mild (GMFCS level I), moderate (II-III), severe (IV-V), any | At 18 months of age |
| Blood transfusion | Number of children receiving bood transfusion during first admission | Assessed up to 18 months of age |
| Deafness | One or both ears | At 18 months of age |
| Odense |
| Fyn |
| 5000 |
| Denmark |
| Gynækologisk-Obstetrisk Afdeling | Aalborg | Jylland | 9100 | Denmark |
| Gynækologisk-obstetrisk afdeling Y | Aarhus | Jylland | 8200 | Denmark |
| Gynækologisk obstetrisk Afdeling | Esbjerg | Jylland | 6700 | Denmark |
| Gynækologisk-obstetrisk afd. | Kolding | Jylland | 6000 | Denmark |
| Gynækologisk obstetrisk afdeling | Randers | Jylland | 8930 | Denmark |
| Gynækologisk-obstetrisk afd. | Silkeborg | Jylland | 8600 | Denmark |
| Kvindeafdeling Y | Viborg | Jylland | 8800 | Denmark |
| Obstetrisk Klinik | Copenhagen | Region Sjælland | 2100 | Denmark |
| Gynækologisk Obstetrisk afdeling | Herlev | Region Sjælland | Denmark |
| Gynækologisk-Obstetrisk Afdeling | Hillerød | Region Sjælland | 3400 | Denmark |
| Gynækologisk Obstetrisk afdeling | Holbæk | Region Sjælland | 4300 | Denmark |
| Gynækologisk-obstetrisk afdeling | Næstved | Region Sjælland | 4700 | Denmark |
| D007752 | Obstetric Labor, Premature |
| D007744 | Obstetric Labor Complications |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D013456 |
| Sulfur Acids |
| D013457 | Sulfur Compounds |