Antenatal Late Preterm Steroids (ALPS): A Randomized Placebo-Controlled Trial
Condition: Pregnancy; Respiratory Distress Syndrome; Pregnancy Outcomes; Preterm Birth
MeSH terms: Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Premature Birth
Intervention: Betamethasone; Placebo
Intervention description: The active study drug, betamethasone. 3 mg per ml betamethasone sodium phosphate 3 mg per milliliter betamethasone acetate The first dose of study drug medication will be administered at randomization as 2 ml injection; the next dose of 2 ml will be administered 24 hours later.; Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.
Intervention MeSH terms: Betamethasone
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 2831.0
Sex: Female
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Betamethasone; Steroids; Perinatology; Late Preterm

Summary:

      This is a randomized placebo controlled trial to evaluate whether antenatal corticosteroids
      can decrease the rate of neonatal respiratory support, thus decreasing the rate of NICU
      admissions and improving short-term outcomes in the late preterm infant. The use of antenatal
      corticosteroids has been shown to be beneficial in women at risk for preterm delivery prior
      to 34 weeks but has not been evaluated in those likely to deliver in the late preterm period
    

Eligibility criteria:

        Inclusion Criteria:

        Singleton Pregnancy. A twin pregnancy reduced to singleton (either spontaneously or
        therapeutically) before 14,0 weeks by project gestational age is acceptable

        Gestational age at randomization between 34,0 weeks and 36,5 weeks confirmed by study
        criteria

        High probability of delivery in the late preterm period (any one of the following):

          -  Membrane rupture as defined by the occurrence of any two of the following: pooling of
             fluid in the vaginal vault, positive Nitrazine test, ferning of vaginal fluid,
             positive AmniSure test; or any one of the following: indigo carmine pooling in the
             vagina after amnioinfustion, visible leakage of amniotic fluid from the cervix

        or

          -  Preterm labor with intact membranes. Preterm labor is defined as at least 6 regular
             uterine contractions in an observation period of no more than 60 minutes and at least
             one of the following: cervix greater than or equal to 3cm dilated or at least 75%
             effaced

        or

          -  Planned delivery by induction of labor or cesarean section in no less than 24 hours
             and no more than 7 days, as deemed necessary by the provider. An induction must be
             scheduled to start by 36,5 weeks at the latest, whereas a cesarean delivery must be
             scheduled by 36,6 weeks at the latest. Therefore the latest gestational age for
             randomization is 36,4 weeks for a planned induction. The planned delivery may be for
             any indication, such as the following: prior myomectomy, prior classical cesarean,
             intrauterine growth restriction (IUGR), oligohydramnios, preeclampsia, nonreassuring
             fetal heart rate tracing warranting delivery, abruption, placenta previa

        Exclusion Criteria:

          1. Any prior antenatal corticosteroid course during the pregnancy because of potential
             contamination of the placebo group

          2. Candidate for stress dose corticosteroids because of chronic steroid therapy to
             prevent suppression of adrenal gland, because of potential contamination of the
             placebo group

          3. Twin gestation reduced to a singleton gestation at or after 14 weeks 0 days by project
             gestational age either spontaneously or therapeutically

          4. Fetal demise, or known major fetal anomaly, including cardiac anomaly and hydrops

          5. Maternal contraindication to betamethasone: hypersensitivity reaction to any
             components of the medication, idiopathic thromboycytopenic purpura, systemal fungal
             infection in case of exacerbation by betamethasone, use of amphotericin B due to the
             possibility of heart failure with concomitant betamethasone

          6. Pre-gestational diabetes - exclude if the patient was on medication (insulin,
             glyburide) prior to pregnancy

          7. Delivery expected within 12 hours of randomization, because of insufficient time of
             corticosteroids to confer benefit, including any of the following:

             A. Rupture of Membranes (ROM) does not satisfy protocol criteria - exclude if the
             patient being evaluated for Preterm Premature Rupture of Membranes (pPROM), does not
             have preterm labor or planned delivery and does not satisfy the spontaneous membrane
             rupture criteria (any 2 of: positive Nitrazine test, pooling of fluid in the vaginal
             vault test or ferning of vaginal fluid; or indigo carmine pooling in the vagina after
             amnioinfusion; or visible leakage of amniotic fluid from the cervix) B. Rupture of the
             membranes in the presence of more than 6 contractions per hour or cervical dilation of
             3 cm or more, unless oxytocin was withheld for at least 12 hours (other induction
             agents allowed) C. Chorioamnionitis - exclude if patient is diagnosed with
             chorioamnionitis D. Cervical dilation ≥ 8 cm E. Evidence of non-reassuring fetal
             status requiring immediate delivery

          8. Participation in another interventional study that influences neonatal morbidity and
             mortality

          9. Participation in this trial in a previous pregnancy

         10. Delivery at a non-network hospital

         11. At 36, 0 weeks to 36, 5 weeks and quota for 36 weeks already met. To ensure there is
             an adequate proportion of women presenting at 34 to 35 weeks of gestation, enrollment
             will be restricted so that no more than 50% of the women in the trial present at 36
             weeks.