Effectiveness of ACS in Extreme Preemies

Effects of Antenatal Corticosteroids in Patients With Early (22 - 23w6d) Threatened Preterm Birth

This is a randomized prospective clinical study that will evaluate the effects of antenatal corticosteroid administration (ACS) vs. placebo in singleton pregnancies who are threatening to deliver prematurely between 22 0/7 and 23 6/7 weeks on admission with the goal of improving composite neonatal mortality and morbidity.

Study Overview

• Status: Withdrawn
• Conditions: Premature Birth; Preterm Labor
• Intervention / Treatment: Drug: Betamethasone; Genetic: Placebo

Detailed Description

The purpose of this study to evaluate the effects of antenatal corticosteroid administration (ACS) vs. placebo in patients who are threatening to deliver prematurely with well-established gestational ages between 22 0/7 and 23 6/7 weeks at the time of admission. If the delivery can be safely delayed at least 3 hours and there is no contraindication to steroid administration, the patient is eligible to be randomized. Randomization will be blinded to the patient and the staff caring for the patient and will be stratified by gestational age: those at 22 0/7 to 22 6/7 weeks and those at 23 0/7 weeks to 23 6/7 weeks. Randomized patients will be assignment to either active drug or placebo at the doses and frequencies below:

• 2 doses of Betamethasone, 12 mg intramuscularly (IM), 24 hours apart, or if as in some hospitals occasionally occurs and betamethasone is unavailable -
• 4 doses of Dexamethasone IM 6 mg, 12 hours apart.

Remainder of care will be at the discretion of the clinician.

Randomized 22 0/7 - 22 6/7:

For patients randomized between 22 0/7 and 22 6/7 weeks and who are undelivered > 24 0/7 weeks, the decision as to whether to administer an additional course or courses of ACS will also be at the discretion of the clinician.

Randomized 23 0/7 to 23 6/7:

For those patients randomized at 23 0/7 to 23 6/7 weeks and who remain undelivered > 24 0/7 weeks and < 1 week after study medication was administered, a second blinded set of medications/placebos will be provided. For patients who received Betamethasone (or dexamethasone) placebo will be provided and for those who received placebo Betamethasone will be provided.(for both at the doses described in 3.4.3). In this group, at any time > 24 0/7 weeks and less than one week of the previous dose, if the clinician feels the patient is still at risk for delivering, this second blinded set of study drugs will be administered. This will allow the patient to receive at least one actual course of ACS if undelivered at 24w0d. In this group, if the patient remains undelivered at > 25 weeks, administration of an open label course of ACS will be at the discretion of the MD.

Primary Outcome of this study is composite morbidity and mortality. The N on this study is 68 (34 in each group)

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• 18 years of age at time of study entry
• Gestational age between 22 0/7 to 23 6/7 weeks, inclusive at time of randomization regardless of whether the provider and patient decide to consider the fetus viable and provide obstetric interventions and cesarean section if needed.
• Singleton pregnancy
• Threatening to deliver by the best estimate of the clinician within the ensuing week
• Thought by the clinician to be able to delay delivery at least 3 hours from the time of randomization.
• Desired Pregnancy

• All clinical complications related to or leading to delivery except those listed as exclusion criteria are eligible. All of the following clinical complications are eligible including but not limited to:

  • premature labor,
  • incompetent cervix with or without prolapsing membranes,
  • Preterm Premature Rupture of the membranes (PPROM),
  • chorioamnionitis,
  • all hypertensive disorders of pregnancy,
  • vaginal bleeding due to placenta previa, abruption or unknown etiology,
  • being delivered for medical complication of pregnancy, and others.

Exclusion Criteria:

• Maternal history of insulin dependent diabetes
• Known congenital fetal anomaly
• Known Hydrops fetalis with this current pregnancy
• Severe intrauterine growth restriction < 10% percentile
• Patient receiving corticosteroids for other maternal indications other than for fetal lung maturity
• Patient with h/o HIV or active Tuberculosis.
• Any other known contraindication to corticosteroids

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Betamethasone; Betamethasone: 12 mg given intramuscularly (IM), 24 hours apart or if as in some hospitals occasionally occurs and betamethasone is unavailable - • 4 doses of Dexamethasone IM 6 mg, 12 hours apart	Drug: Betamethasone; Course of ACS given intramuscularly (2 doses of 12 mg, 24 hours apart); Other Names: ACS
PLACEBO_COMPARATOR: Normal Saline; Quantity Sufficient (QS) of Normal Saline (NS) given intramuscularly (IM), 24 hours apart or if hospital is using Dexamethasone in place of Betamethasone then administer NS x 4 doses 12 hours apart	Genetic: Placebo; Course of placebo drug given intramuscularly (2 doses of normal saline (of equal quantity) 24 hours apart).; Other Names: Normal Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite Neonatal Morbidity	Defined as one or more of the following: fetal death, neonatal death within 30 days of delivery, respiratory distress syndrome (oxygen requirement, clinical diagnosis and consistent chest x-ray), bronchopulmonary dysplasia (requirement for oxygen support at 30 days of life), severe intraventricular hemorrhage (IVH) (grades III or IV), periventricular leukomalacia, blood culture proven sepsis, necrotizing enterocolitis (NEC).	First 30 days after birth

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preterm Birth prior to 34weeks gestational age.	Preterm birth that occurs between the time of enrollment into the study (22w0d-23w6d) until 34w6d.	From entry into the study until 34 weeks gestational age.
Respiratory Distress Syndrome (RDS)	RDS is defined as compatible symptoms with radiographically confirmed hyaline membrane disease or  with respiratory insufficiency of prematurity requiring ventilator support are present.	First 30 days after birth
Birth Weight	newborns birth weight	Measured at time of birth
Newborn Head Circumference measurement	Measurement of newborn head circumference done at time of birth.	Measured at time of birth
Need for Newborn Surfactant Therapy	administration of newborn surfactant therapy within the first 30day of life.	First 30 days after birth

Collaborators and Investigators

• Sponsor: Pediatrix
• Investigators: Study Director: Thomas J Garite, MD, Pediatrix

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (ACTUAL): November 1, 2015
• Study Completion (ACTUAL): November 1, 2015

Study Registration Dates

• First Submitted: January 27, 2015
• First Submitted That Met QC Criteria: January 27, 2015
• First Posted (ESTIMATE): January 30, 2015

Study Record Updates

• Last Update Posted (ESTIMATE): March 14, 2016
• Last Update Submitted That Met QC Criteria: March 11, 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; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Asthmatic Agents; Respiratory System Agents; Betamethasone
• Other Study ID Numbers: OBX0031

Plan for Individual participant data (IPD)

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