The Effect of Low Doses of Prednisone on the Prolongation of Pregnancy in Threatened Preterm Birth

The Effect of Low Doses of Intermediate Acting Corticosteroids on the Prolongation of Pregnancy in Threatened Preterm Birth

The goal of this clinical trial is to test the effect of low dose of prednisone in prevention of preterm labour in single pregnancies. The main question it aims to answer is does prednisone prolong singleton pregnancy in threatened preterm birth and reduce mortality and morbidity of newborns, without harmful consequences for mother and the foetus. Participants will be:

• administered low dose of prednisone in a period of total 3 weeks on top of standard therapy
• drown blood for standard laboratory tests
• cervical swab and urine for urinoculture will be taken and
• asked to sign Informed Consent Researcher will compare low dose of prednisone to standard therapy

Study Overview

• Status: Not yet recruiting
• Conditions: Preterm Birth
• Intervention / Treatment: Drug: Prednisone 5Mg

Detailed Description

Prematurity is the leading causes of infant mortality and is associated with an increased risk of respiratory, neurological and metabolic disorders in survivors. Approximately 15 million babies are born preterm annually worldwide. Despite the rapid development of pharmacotherapy, there was no significant decline in the premature birth (PTB) rates. So far, the most useful intervention for improving neonatal outcomes in premature children has been the antenatal administration of long-acting corticosteroids (CSs). Although the underlying causes of PTB are numerous, it is well established that infection and inflammation represent a highly significant risk factor for spontaneous PTB, characterized by the significant production of inflammatory mediators that lead to weakening of the foetal membranes, cervical stroma and contraction of the myometrium. There is increasing evidence of the presence of sterile inflammation (intra-amniotic inflammation without the presence of microorganisms) in PTB with both intact membranes and preterm premature rupture of membranes (PPROM). CS and non-steroidal anti-inflammatory drugs (NSAID) are used today to treat most inflammatory diseases. NSAID are used as tocolytics. Indomethacin, one of the most commonly used NSAID tocolytics has been associated with oligohydramnios and premature closure of the foetal ductus arteriosus when used for prolonged period. As far back as 1972, Liggins and Howie proved that antenatal administration of CS reduces the incidence and severity of respiratory distress syndrome (RDS) and mortality of premature infants. Meta-analyses have confirmed a lower rate of intraventricular haemorrhage and necrotic enterocolitis in premature infants whose mothers received RDS prophylaxis. Therefore, their application proved to be the most useful intervention for improving neonatal outcome in threatening PTB.Today, a CS is a part of standard therapy for the treatment of systemic autoimmune diseases and act as suppressors of immune response. Long acting CSs cross the placental barrier and are used to treat the foetus (foetal lupus, congenital adrenal hyperplasia, prevention of respiratory distress syndrome), and intermediate acting drugs are used to treat maternal diseases as they have a low affinity for passing through the placenta.The effect of low doses of intermediate acting corticosteroids on the prolongation of pregnancy in threatened preterm birth has not yet been studied.Given that PTB is a syndrome characterized by a strong inflammatory response, we present the hypothesis that low doses of an intermediate acting CS for 3 weeks after tocolysis and RDS prophylaxis help prolong singleton pregnancy in women with threatening PTB, without harmful consequences for mother and child.

• Study Type: Interventional
• Enrollment (Estimated): 26
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Nikolina Penava, MD; Phone Number: 0038763818875; Email: npenava@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Singleton pregnancies in 24th until 34th week of gestation with a sign of threatening preterm birth at the time of admission: uterine contractions more than 4 in 20 minutes or more than 8 in 60 minutes with concomitant bleeding accompanied by cervical dilation more than 2 cm, cervical effacement less than 20 mm using transvaginal probe, progression in gynecological findings at the time of admission.

Exclusion Criteria:

• Contraindications for tocolysis and continuation of systemic CS administration that include all conditions in which prolongation of the pregnancy increases the risk for foetus or/and the mother (i.e. intrauterine growth restriction, lethal foetal anomaly, non/reassuring foetal status, preeclampsia with severe features or eclampsia, maternal hemorrhage with haemodynamic instability, intraamniotic infections/chorioamnionitis), uncontrolled diabetes, severe liver impairment and preterm prelabour rupture of membranes.

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
Experimental: Low dose of prednisone group; Low doses of an intermediate acting corticosteroids (CS) administered three weeks after two-day tocolysis and respiratory distress syndrome (RDS) prophylaxis, plus neuroprotection with magnesium sulphate.	Drug: Prednisone 5Mg; Prednisone administered for three weeks. If pregnant women weighs less than 90 kg , she will receive prednisone on altering days instead of every morning for pregnant women weighing more than 90 kg.
Active Comparator: Standard therapy group; Two-day tocolysis and RDS prophylaxis, plus neuroprotection with magnesium sulphate.	Drug: Prednisone 5Mg; Prednisone administered for three weeks. If pregnant women weighs less than 90 kg , she will receive prednisone on altering days instead of every morning for pregnant women weighing more than 90 kg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of days by which singleton pregnancies with threatened preterm birth are prolonged	Prolongation of singleton pregnancy in threatened preterm birth	10 weeks (from 24th till 34th week of pregnancy)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of mortality and morbidity	Change mortality and morbidity of newborns without harmful consequences for the mother and the foetus.	10 weeks (from 24th till 34th week of pregnancy)

Collaborators and Investigators

• Sponsor: University of Mostar

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2023
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: October 21, 2023
• First Submitted That Met QC Criteria: October 21, 2023
• First Posted (Actual): October 26, 2023

Study Record Updates

• Last Update Posted (Actual): October 30, 2023
• Last Update Submitted That Met QC Criteria: October 26, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Premature birth, sterile inflammation, prednisone
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Premature Birth; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone
• Other Study ID Numbers: 1236/22

Plan for Individual participant data (IPD)

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

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