Different Schemes of Magnesium Sulfate for Preeclampsia

Study Overview
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Brief Summary
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Eclampsia is an obstetric emergency capable of prophylaxis. To prevent and control seizures, there is no doubt that the magnesium sulfate (MgSO4) is the ideal drug. However, there are still questions regarding its use and dose. The scheme and the optimal time of administration remain to be elucidated. The objective of this trial is to compare the effectiveness and safety of intravenous magnesium sulfate in the maintenance phase 1g / h versus 2 g / h to prevent eclampsia in pregnant and postpartum women with severe preeclampsia (pure or superimposed).

Detailed Description
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Hypertensive disorders are frequent during the course of pregnancy-puerperal cycle and an important cause of maternal morbidity and mortality, fetal and perinatal. The high frequency of maternal death can be explained by the presence of numerous complications such as eclampsia. Eclampsia is an obstetric emergency capable of prophylaxis. To prevent and control seizures, there is no doubt that the magnesium sulfate (MgSO4) is the ideal drug. However, there are still questions regarding its use and dose. The scheme and the optimal time of administration remain to be elucidated. Currently, allows the use of either 1 g / h to 2 g / h of magnesium sulphate during the maintenance phase to prevent eclamptic convulsions. However, there is no report in the literature of randomized controlled trials comparing different doses of magnesium sulfate in the maintenance phase to prevent eclampsia. The objective of this study is to compare the effectiveness and safety of intravenous magnesium sulfate in the maintenance phase 1g / h versus 2 g / h to prevent eclampsia in pregnant and postpartum women with severe preeclampsia (pure or superimposed).There will be a trial randomized and triple blind in the Integrative Medicine Institute Prof. Fernando Figueira (IMIP) from March 2015 to April 2017, and will be included 2000 women randomized into two groups: MgSO4 maintenance dose of 1 g / h or 2 g / h. Patients who had eclampsia before loading dose, with use of other medications or illicit drugs that may interfere with maternal hemodynamics or with contraindications to the use of magnesium sulfate will be excluded. The primary endpoint will be the incidence of eclampsia. Other complications such as oliguria, bleeding, recurrence of seizures, disseminated intravascular coagulation, maternal death, presence of side effects related to the use of MgSO, neonatal outcome and other variables will be considered secondary outcomes. Randomization for preventive treatment of eclamptic seizures with MgSO4 1g / h or MgSO4 2g / h will be held according to a table of sequential numbers from one to 2000, using the letters A and B and not knowing its meaning. The analysis will be performed with the groups identified as A or B, breaking the secrecy only after the results obtained and prepared the tables, or by resolution of the External Monitoring Committee.

Official Title
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Effectiveness and Safety of 1g/Hour vs. 2g/Hour of Magnesium Sulfate Maintenance Dose for Eclampsia Prevention: Randomized Clinical Trial

Conditions
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Preeclampsia

Intervention / Treatment
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* Drug: Magnesium sulfate 50% - 1g/h
* Drug: Magnesium sulfate 50% - 2g/h


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Severe Preeclampsia (pure and superimposed) Exclusion Criteria: Eclampsia before administration of the loading dose of MgSO4 ; Use of other medications or illicit drugs that may interfere with maternal hemodynamics; Contraindications to the use of magnesium sulfate: known hypersensitivity to the drug, oliguria with urine output below 25 ml per hour or anuria (urine output absent) and myasthenia gravis. Use of mechanical ventilation

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Magnesium sulfate 50% - 1g/h<br>After loading dose of 6g of magnesium sulfate, patients will receive the maintenance dose of 1g/hour of intravenous magnesium sulfate, for 24 hours | Drug: Magnesium sulfate 50% - 1g/h<br>* Patients will receive after the loading dose os magnesium sulfate, the maintenance dose of 1g/hour of intravenous of magnesium sulfate for 24 hours after loading dose<br>* Other names: Mg SO4;|
| Experimental: Magnesium sulfate 50% - 2g/h<br>After loading dose of 6g of magnesium sulfate, patients will receive the maintenance dose of 2g/hour of intravenous magnesium sulfate, for 24 hours | Drug: Magnesium sulfate 50% - 2g/h<br>* Patients will receive after the loading dose os magnesium sulfate, the maintenance dose of 1g/hour of intravenous of magnesium sulfate for 24 hours after loading dose<br>* Other names: MgSO4;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ECLAMPSIA | Seizures that occur after the loading dose, during magnesium sulfate, until 24 hours after the delivery of the baby | From end of loading dose, until 24 hours after delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Placental abruption | Occurence of placental abruption | From end of loading dose, until delivery of the child | 
| postpartum hemorrhage | Occurence of postpartum hemorrhage, diagnosed clinically by the attending phisician | From end of loading dose, until 48 hours after delivery | 
| COMPLICATIONS | Occurence of a retained placenta | From end of loading dose, until 3 hours after delivery | 
| thromboembolic complications | Diagnosis of thromboembolic complications bay doppler compression ultrasound or CT | From end of loading dose, until 15 days after delivery | 
| liver failure | Occurence of liver failure according to laboratorial exams | From end of loading dose, until 15 days after delivery | 
| OLIGURIA | Oliguria diagnosed as the presence of urine output under 0.5 (mililiters per kilogram) mL/kg for six hours, | From end of loading dose, until 15 days after delivery | 
| RENAL FAILURE | Occurence of renal failure diagnosed as the presence of oliguria for more than 24 hours or elevation serum creatinine (3X ) | From end of loading dose, until 15 days after delivery | 
| Disseminated intravascular coagulation (DIC) | Presence of disseminated intravascular coagulation | From end of loading dose, until 15 days after delivery | 
| acute pulmonary edema | Presence of clinically diagnosis of acute pulmonary edema | From end of loading dose, until 15 days after delivery | 
| Maternal death | Maternal death occuring for direct obstetric causes | From end of loading dose, until 42 days after delivery | 
| Composite maternal morbidity | Presence of one of the investigated complications | From end of loading dose, until 42 days after delivery | 
| RECURRENCE | Recurrence of seizures after loading dose of magnesium sulfate | From end of loading dose, until 24 hours after delivery | 
| additional anticonvulsant | Need for additional anticonvulsant after the use of magnesium sulfate | From end of loading dose, until 24 hours after delivery | 
| SIDE EFFECTS | Presence of side effects of magnesium sulfate use | From end of loading dose, until 24 hours after delivery | 
| DISCONTINUATION OF MAGNESIUM SULFATE | Occurence of discontinuation of treatment due to side effects | From end of loading dose, until 24 hours after delivery | 
| GLUCONATE USE | Need for the use of calcium gluconate | From end of loading dose, until 24 hours after delivery | 
| MAGNESIUM LEVELS | Serum magnesium levels evaluated at the beginning of maintenance dose and after 30. minutes, every 2 hours for six hours and after every six hours until 24 hous after loading dose. This outcome will be evaluated in the first 62 patients | From end of loading dose, until 24 hours after delivery | 
| Hypertensive crises | Presence of hypertensive crises and need for antihypertensive drugs and need to continue therapy for more than 24 hours. | From end of loading dose, until 24 hours after delivery |