Nifedipine Plus Magnesium Sulfate Versus Magnesium Sulfate for Very Early Preterm Tocolysifs

Study Overview
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Brief Summary
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Objective: This trial is designed to compare between the effectiveness of nifedipine plus magnesium sulfate (MgSO4) and MgSO4 alone for tocolysis in women with threatened preterm labor. Patient Population: The population will include pregnant women at gestational age between 28 and 31 weeks who are 18 years old or older and have signs of threatened preterm labor. Study Design: This is a single-center, prospective, randomized controlled clinical trial. A total of 264 women pregnant between 28 and 31 weeks having threatened preterm labor will be enrolled and randomized into two parallel treatment arms. Patients in the group A will receive nifedipine plus MgSO4, while patients in group B will MgSO4 only. Treatment: All patients will be randomized on the day of enrollment. Patients with threatened preterm labor will receive the respective tocolysis in each group. All patients will receive corticosteroids for lung maturity according to the local protocol. Primary outcome: Number of women not delivered within 48 hours of starting tocolytic therapy. Secondary outcomes: perinatal mortality, a composite of adverse neonatal outcomes, birth weight, days on ventilation support, length of admission in neonatal intensive care, prolongation of pregnancy more than 7 days, delivery after 37 weeks of gestation, number of days till delivery, maternal mortality, maternal infection, and harm to mother from intervention.

Official Title
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Nifedipine Plus Magnesium Sulfate Versus Magnesium Sulfate Alone for Tocolysis in Pregnant Women at 28 - 31 Weeks Gestation With Threatened Preterm Labor

Conditions
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Threatened Preterm Labor

Intervention / Treatment
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* Drug: Nifedipine 20 Mg
* Drug: Magnesium sulfate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women with threatened preterm labor defined as 3 or more uterine contractions in 30 minutes confirmed by cardiotocography. Gestational age from 28 week + 0 days to (inclusive) 31 weeks + 6 days. Women with singleton or multiple pregnancy. Women with preterm prelabor rupture of membranes (PROM) will be included if they have uterine contractions. Exclusion Criteria: Contraindications for the use of either drugs, such as cardiac disease, hypotension, myasthenia gravis, or renal impairment. Contraindications for tocolysis, such as intrauterine demise, intrauterine infection, fetal distress, placental separation, or severe pre-eclampsia. Cervical dilatation > 5 cm. Cervical length > 30 mm by trans-vaginal ultrasound. Cervical cerclage.

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>Nifedipine + Magnesium sulfate | Drug: Nifedipine 20 Mg<br>* The initial dose of nifedipine will be 2 × 10 mg nifedipine capsules orally in the first hour, followed by 20 mg slow-release nifedipine every 6 hours for the next 47 hours. In the first hour after starting nifedipine, blood pressure and heart rate will be measured every 15 minutes. If blood pressure remains within the normal limits, treatment will be continued.<br>Drug: Magnesium sulfate<br>* Women will also receive MgSo4 as a loading dose of MgSo4 will be given immediately after enrollment as 4 gm diluted in 200 mL of saline solution administered intravenous over a period of 20 minutes. Afterwards, the maintenance dose of MgSo4 will be administered intravenous in a dose of 1 gm/hour given as 6 gm diluted in 500 mL saline solution titrated with a rate of 100 mL per hour, then this dose is repeated every 6 hours for 48 hours. Respiratory rate and knee jerk will be assessed hourly for women in the MgSo4 group. Serum magnesium level will be measured if clinically indicated.<br>|
| Active Comparator: B<br>Magnesium Sulfate | Drug: Magnesium sulfate<br>* Women will also receive MgSo4 as a loading dose of MgSo4 will be given immediately after enrollment as 4 gm diluted in 200 mL of saline solution administered intravenous over a period of 20 minutes. Afterwards, the maintenance dose of MgSo4 will be administered intravenous in a dose of 1 gm/hour given as 6 gm diluted in 500 mL saline solution titrated with a rate of 100 mL per hour, then this dose is repeated every 6 hours for 48 hours. Respiratory rate and knee jerk will be assessed hourly for women in the MgSo4 group. Serum magnesium level will be measured if clinically indicated.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of women not delivered within 48 hours of starting tocolytic therapy. | postponing delivery for at least 48 hours to allow the time for corticosteroid administration for fatal lung maturity | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Perinatal mortality | Death of the offspring during treatment, labor or neonatal period | From starting treatment until 1 month of delivery | 
| A composite of adverse neonatal outcomes | convulsions, apnoea, asphyxia, proven meningitis, pneumothorax or sepsis | within 1 month of delivery | 
| days on ventilation support | number of days on mechanical ventilation | within 1 month of delivery | 
| length of admission in neonatal intensive care | Number of days in the NICU | within 1 month of delivery | 
| Prolongation of pregnancy more than 7 days | Number of women not delivering after at least 7 days from starting the intervention | 7 days after initiation of therapy | 
| Delivery after 37 weeks of gestation. | number of women delivered after 37 weeks of gestation | after 37th week of delivery | 
| Number of days till delivery |  | from starting the intervention until delivery | 
| Maternal mortality rate | Number of maternal deaths during pregnancy, labor or puerperium | from starting treatment until 1 month after delivery | 
| Maternal infection rate | Number of women having Chorioamnionitis, Puerperal sepsis, endometritis, or sepsis | from starting treatment until 1 month after delivery | 
| Harm to mother from interventions (side effects) | admission to intensive care, anaphylactic shock, dyspnoea, hypotension (leading to cardiotocography abnormalities), liver test abnormalities (elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT)), general side effects (nausea, vomiting, headache) and postpartum haemorrhage defined as >500 mL blood loss | from starting treatment until 1 month after delivery |