Tocolytic Therapy for Preterm Labor in Multiple Gestation

To compare the tocolytic efficacy oxytocin receptor antagonist (Atosiban) with that of calcium channel blockers (Nifedipine) among women with multiple gestation who present with threatened preterm labor.

Study Overview

• Status: Unknown
• Conditions: Labor Preterm Multiple
• Intervention / Treatment: Drug: Atosiban; Drug: Nifedipine

Detailed Description

Preterm birth remains the principal cause of early neonatal death. Infants born preterm (before 37 weeks' gestation) often suffer significant immediate morbidity and need lengthy stays in neonatal intensive care units. Moreover, there is a significant risk of long-term neurological morbidity in a proportion of the survivors. Patients with a multiple gestation are at significant risk for preterm labor and delivery as approximately 60% of all those pregnancies will be delivered preterm.

A number of oxytocin receptor antagonists have been developed, and of these, three, atosiban, barusiban and retosiban have been investigated in humans as tocolytic agents. To date, only atosiban is in use outside of clinical trials. Atosiban is an oxytocin receptor antagonist which was specifically developed for the treatment of preterm labor. Early reports of the use of Atosiban for tocolysis showed promise both in vitro and in animal studies, and preliminary studies in pregnant and non-pregnant humans suggested a very low incidence of maternal side effects .

• Study Type: Interventional
• Enrollment (Anticipated): 140
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Twin pregnancy
2. Gestational age between 24+0 and 32+6 weeks
3. Intact amniotic membranes
4. Threatened preterm labor
5. Age 18-50.

Exclusion Criteria:

1. Rupture of membranes
2. Vaginal bleeding resulting from placenta previa or placental abruption
3. Fever above 38°C
4. Severe preeclampsia
5. Maternal cardiovascular or liver diseases
6. Systolic blood pressure less than 90 mm Hg
7. Known uterine malformation
8. Intrauterine growth restriction below the fifth percentile
9. Non-reassuring fetal status
10. Antepartum diagnosis of major fetal malformations
11. Fetal death
12. Previous tocolytic therapy or Betamethasone treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Atosiban; Women with twin pregnancy with preterm labor between 24 weeks 0 days and 32 weeks 6 days of gestation will be included and randomly assigned to the Atosiban group.	Drug: Atosiban; After random allocation to a treatment group, women will receive Atosiban as follows: Atosiban was given as a single loading intravenous dose, 6.75 mg in 0.9% sodium chloride solution, followed by an intravenous infusion of 300 micrograms/min in 0.9% sodium chloride solution for the first 3 hours and then 100 micrograms/min for another 45 hours. The choice of the dose regimen for Atosiban was consistent with the recommendations of the product labeling.
EXPERIMENTAL: Nifedipine; Women with twin pregnancy with preterm labor between 24 weeks 0 days and 32 weeks 6 days of gestation will be included and randomly assigned to the Nifedipine group.	Drug: Nifedipine; After random allocation to a treatment group, women will receive Nifedipine as follows: Nifedipine was given as a loading dose of 20 mg orally followed by another two doses of 20 mg, 20-30 minutes apart as needed. Maintenance was started after 6 hours with 20-40 mg four times a day for a total of 48 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Duration of labor	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infant morbidity	Defined as the number of infant morbidity up to 28 days from birth.	28 days
Chronic lung disease	Defined as the number of participants with need for supplemental oxygen at 28 days of life	28 days

Collaborators and Investigators

• Sponsor: Tel-Aviv Sourasky Medical Center

Publications and helpful links

General Publications

• Wilson A, Hodgetts-Morton VA, Marson EJ, Markland AD, Larkai E, Papadopoulou A, Coomarasamy A, Tobias A, Chou D, Oladapo OT, Price MJ, Morris K, Gallos ID. Tocolytics for delaying preterm birth: a network meta-analysis (0924). Cochrane Database Syst Rev. 2022 Aug 10;8(8):CD014978. doi: 10.1002/14651858.CD014978.pub2.

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (ANTICIPATED): March 1, 2018
• Study Completion (ANTICIPATED): March 1, 2018

Study Registration Dates

• First Submitted: March 22, 2016
• First Submitted That Met QC Criteria: March 28, 2016
• First Posted (ESTIMATE): April 1, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): April 1, 2016
• Last Update Submitted That Met QC Criteria: March 28, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Premature Birth; Obstetric Labor, Premature; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Membrane Transport Modulators; Hormone Antagonists; Calcium-Regulating Hormones and Agents; Reproductive Control Agents; Calcium Channel Blockers; Tocolytic Agents; Nifedipine; Atosiban
• Other Study ID Numbers: 755-15-TLV

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO