Nifedipine Plus Magnesium Sulfate Versus Magnesium Sulfate for Very Early Preterm Tocolysifs (ASTOS1)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Threatened Preterm Labor
• Intervention / Treatment: Drug: Nifedipine 20 Mg; Drug: Magnesium sulfate

• Study Type: Interventional
• Enrollment (Estimated): 264
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Karim S Abdallah, MD; Phone Number: +201270595485; Email: karimsayed88@aun.edu.eg

Study Locations

• Egypt
  • Assiut, Egypt, 71111
    • Recruiting
    • Assiut University
    • Contact: Karim Abdallah, MD; Phone Number: +201000024188; Email: karimsayed88@aun.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A; Nifedipine + Magnesium sulfate	Drug: Nifedipine 20 Mg; 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.; Drug: Magnesium sulfate; 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.
Active Comparator: B; Magnesium Sulfate	Drug: Magnesium sulfate; 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.

What is the study measuring?

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
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
Delivery after 37 weeks of gestation.	number of women delivered after 37 weeks of gestation	after 37th week of delivery

Collaborators and Investigators

• Sponsor: Assiut University

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2022
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: April 8, 2022
• First Submitted That Met QC Criteria: April 19, 2022
• First Posted (Actual): April 25, 2022

Study Record Updates

• Last Update Posted (Actual): December 8, 2023
• Last Update Submitted That Met QC Criteria: December 3, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Premature Birth; Obstetric Labor, Premature; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Vasodilator Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Membrane Transport Modulators; Anticonvulsants; Calcium-Regulating Hormones and Agents; Reproductive Control Agents; Calcium Channel Blockers; Tocolytic Agents; Magnesium Sulfate; Nifedipine
• Other Study ID Numbers: ASsiut TOcolytic Study 1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No