Oxidative Stress in Women Treated With Atosiban for Impending Preterm Birth

Evaluation of Oxidative and Antioxidative Status of Pregnant Women Suffering From Threatened Preterm Birth During Tocolytic Treatment With Atosiban

Oxidative stress is recognized as a important factor in the pathogenesis premature birth. Preterm birth is defined as delivery before 37 completed weeks of gestation and it is the leading cause of neonatal morbidity and mortality. The investigators conducted this analysis to investigate the safety of administration of Atosiban - a reversible, competitive antagonist of the oxytocin receptor in the treatment of preterm labor and its impact on the level of oxidative stress after 48 hours of tocolytic treatment.

Study Overview

• Status: Completed
• Conditions: Premature Birth
• Intervention / Treatment: Drug: Atosiban

Detailed Description

Atosiban (1-(3-mercaptopropanoic acid)-2-(O-ethyl-D-tyrosine)-4-L-threonine-8-L-ornithine-oxytocin) is licensed for clinical use in women suffering from threatened premature birth and is widely used in clinical practice in Europe because of its low side effect profile. The impact of Atosiban on pregnancy outcomes in women has been investigated in recent years and the research has shown its ability to reduce intracytoplasmic calcium release and downregulate prostaglandin synthesis as oxytocin receptor antagonist. While a role of Atosiban in the modulation of myometrial contractility is well-described, its effect on many other functions is not so well known.

The serum and plasma samples take for the measurement of total oxidant status (TOS), total antioxidant status (TAS), level of 3-nitrotyrosine (3-NT), and carbonyl and thiol groups will be stored at -70°C in aliquots for subsequent biochemical analysis and processed within two months.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Poland
  • Łódź, Poland, 93-338
    • Department of Obstetrics, Perinatology and Gynecology, Polish Mother's Memorial Hospital-Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• pregnant women between 24-35 weeks' gestation receiving prenatal care due to the risk of premature birth
• intact membranes
• evidence of premature labor (regular, painful and persistent uterine contractions; cervical changes)

Exclusion Criteria:

• acute fetal distress
• other conditions requiring immediate delivery (eclampsia and severe pre-eclampsia, placenta previa, abruptio placenta)
• vaginal bleeding,
• premature rupture of membranes
• chorioamnionitis,
• fetal congenital malformations,
• intrauterine growth restriction,
• the use of any tocolytic drugs during pregnancy before admission to the hospital
• circulatory system diseases (e.g. heart defects, hypertension),
• symptoms of infection
• other diseases that may increase oxidative stress

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Atosiban; Total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI) values as well as 3-nitrotyrosine, carbonyl and thiol groups levels weill be measure using ELISA test in serum and plasma of 64 pregnant women before and after 48 hours of continuous administration of Atosiban.

Drug: Atosiban; The initial dose of Atosiban (Tractocile, Ferring Pharmaceuticals A/S, Copenhagen, Denmark) will be give as a single intravenous bolus dose (6.75 mg in 0.9 ml isotonic sodium chloride solution). This will be follow immediately by intravenous infusion of 300 μg/min of Atosiban in 5% glucose for 3 hours, and then 100 μg/min for up to 48 hours. Venous blood samples from a forearm vein will take before and after 48 hours of continuous administration tocolytic therapy with Atosiban.; Other Names: Tractocile

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delay preterm delivery for 48 hours	Delay preterm delivery for 48 hours, thus allowing administration of corticosteroids to induce surfactant production in fetal lungs and improve neonatal outcome	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Apgar score	Apgar score	At birth
Weight	Weight	At birth
Incidence of duration of hospitalization	Incidence of duration of hospitalization	Up to 28 days after birth
Time to delivery measured from start of Atosiban administration	Time to delivery measured from start of Atosiban administration	Up to 15 weeks from start of Atosiban administration

Collaborators and Investigators

• Sponsor: Polish Mother Memorial Hospital Research Institute
• Investigators: Principal Investigator: Mariusz Grzesiak, Ph.D. MD, Department of Obstetrics, Perinatology and Gynecology, Polish Mother's Memorial Hospital-Research Institute

Publications and helpful links

General Publications

• Grzesiak M, Gaj Z, Kocylowski R, Suliburska J, Oszukowski P, Horzelski W, von Kaisenberg C, Banach M. Oxidative Stress in Women Treated with Atosiban for Impending Preterm Birth. Oxid Med Cell Longev. 2018 Dec 2;2018:3919106. doi: 10.1155/2018/3919106. eCollection 2018.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2014
• Primary Completion (Actual): June 10, 2018
• Study Completion (Actual): December 30, 2018

Study Registration Dates

• First Submitted: June 15, 2018
• First Submitted That Met QC Criteria: June 25, 2018
• First Posted (Actual): June 26, 2018

Study Record Updates

• Last Update Posted (Actual): June 14, 2019
• Last Update Submitted That Met QC Criteria: June 13, 2019
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Reproductive Control Agents; Tocolytic Agents; Atosiban
• Other Study ID Numbers: 2015/I/17-GW

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Study protocol, statistical analysis plan, informed consent form, clinical study report

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No