Please select the eligibility criteria that correspond to the clinical trial below.
Title: Utility of Tocolytic Therapy for Maintenance Tocolysis in the Management of Threatened Preterm Delivery
Brief Summary: Hypothesis: Both nifedipine or progesterone are widely used in clinical practice as maintenance tocolytic therapy after an episode of threatened preterm delivery. Nevertheless, there is insufficient evidence to justify its routine use. The present study aims to evaluate the efficacy and safety of these tocolytic drugs for maintenance tocolysis in the management of threatened preterm delivery.

Materials and methods:

Phase III clinical trial, which evaluates the efficacy and safety of nifedipine and progesterone as maintenance tocolytic therapy until the 34th week of pregnancy in randomized women after an episode of threatened preterm delivery.

Pregnant women with singleton pregnancies are going to be evaluated, with intact membranes and cervical length less than or equal to 25 mm, which have received acute tocolysis with atosiban. They will be randomized to receive maintenance tocolysis with nifedipine (60 mg / day orally) or progesterone (200 mg / day vaginally) until week 34 of gestation. Therefore all included patients will receive treatment with proven but not agreed efficacy, to decrease the recurrence of threatened preterm delivery, prolongation of gestation and subsequent better perinatal outcome. During the course of pregnancy, patients will be monitored in outpatient obstetrics, thus checking an adequate compliance. Monitoring will continue until the end with the delivery and collection of newborn data.

The study will be single-blind, since there will be a blind evaluator. The drugs or treatments not allowed before and / or during the clinical trial are those which are indicated in the data sheet for each drug. If the patient takes antihypertensive treatment and continues it during pregnancy, dose adjustment will be done if it is needed.

Data will be collected in the case report data (CRD). The end of the test will be considered when the last recruited patient complete the gestation (delivered vaginally or cesarean), and all data from newborn are collected. If a serious adverse event occurs in a patient, the woman will immediately finish the clinical trial and will be followed until complete resolution of the episode.

Treatment is going to be considered effective if the birth occurs after 37 weeks of pregnancy with satisfactory perinatal outcome. The drugs are going to be considered safe if they do not cause adverse events in pregnant women, or if they are not serious.

Number of Subjects: 50 pregnant women

Diagnosis and main criteria for inclusion and exclusion:

Inclusion Criteria

* Pregnant women with singleton pregnancies and intact membranes which have passed an episode of threatened preterm delivery (uterine contractions with cervical change) successfully treated with atosiban as acute tocolytic therapy.
* Cervical length ≤ 25 mm. Exclusion Criteria
* ≥ 3 cm cervical dilation, multiple pregnancy, maternal medical contraindication to tocolysis with nifedipine, atosiban or progesterone, or obstetric contraindication to tocolytic treatment (severe preeclampsia, intrauterine infection, placental abruption, fetal abnormality incompatible with life, fetal death) .

Investigational product, dose and mode of administration: After a successful treatment of acute preterm labor with atosiban, is will be compared the safety and efficacy of maintenance tocolytic therapy with nifedipine 60 mg / day orally or progesterone 200 mg / day vaginally.

Therapeutic group: C08CA05 Nifedipine. G03DA04 micronized progesterone.

Route of administration: nifedipine orally. Progesterone vaginally.

Dose: Nifedipine 60 mg / day. Progesterone 200 mg / day.

Duration of treatment: From the resolution of acute episode of threatened preterm labor until 34 weeks of gestation.

Reference treatment, dose and mode of administration: Current evidence questions the utility of maintenance tocolytic therapy. No reference treatment is currently defined.


Options:
A: Inclusion Criteria:

* Pregnant women with singleton pregnancies and intact membranes which have passed an episode of threatened preterm delivery (uterine contractions with cervical change) successfully treated with atosiban as acute tocolytic therapy.
* Cervical length ≤ 25 mm.

Exclusion Criteria:

* ≥ 3 cm cervical dilation, multiple pregnancy, maternal medical contraindication to tocolysis with nifedipine, atosiban or progesterone, or obstetric contraindication to tocolytic treatment (severe preeclampsia, intrauterine infection, placental abruption, fetal abnormality incompatible with life, fetal death)
B: Key Inclusion Criteria:

Part A

* Pregnant females aged ≥ 18 years
* Patients with a singleton or twin pregnancy
* Gestational age between 28 0/7 and 33 6/7
* Administered or prescribed atosiban for the treatment of preterm labour

Part B

* Pregnant females aged ≥ 18 years
* Patients with a singleton or twin pregnancy
* Gestational age between 24 0/7 and 33 6/7
* Administered or prescribed atosiban for the treatment of preterm labour
* ≥4 uterine contractions per 30 minutes
* Cervical dilatation of 1 to 4 cm inclusive
* At least one of the following signs of preterm labour:

  1. positive IGFBP-1 or fœtal Fibronectin test
  2. cervical length ≤ 25mm
  3. progressive cervical change

Key Exclusion Criteria:

* Fœtal death in utero in current or previous pregnancy after gestational week 24 or expected high risk of fœtal death in the coming days
* Oligohydramnios
* Known pathological Doppler ultrasound of the umbilical artery
* Any contraindications for the mother or the fœtus to stop labour or prolong pregnancy or any maternal or fœtal conditions likely to indicate iatrogenic delivery in the next 7 days, including but not limited to:

  1. Premature rupture of membranes
  2. Evidence or suspicion of abruptio placenta
  3. Signs and/or symptoms of chorio-amnionitis
  4. Pre-eclampsia, eclampsia or HELLP-syndrome
* Use of cervical cerclage in the current pregnancy or a pessary in situ
* Current use of anti-hypertensive medication
* Treatment with other tocolytics within specified time before the baseline assessment of uterine contractions
C: Inclusion Criteria:

* Pregnancy between completed 24 to 24 weeks
* Successfully treated episode of threatened preterm labour by intravenous preparations
* No uterine contractions

Exclusion Criteria:

* Uterine contractions (painful, clinically palpable, or present on cardiotocography)
* Cervical dilatation of ≥5 cm
* Clinical and laboratory signs of infection defined as offensive vaginal discharge on clinical examination, vaginal pH ≥5, white blood cell (WBC) count \>16×109/L, and C-reactive protein (CRP) \>10 mg/L
* Positive findings of microorganisms rather than normal vaginal flora on high vaginal swab
* Any signs of fetal distress according to cardiotocography, Doppler assessment of blood flow in umbilical artery, and biophysical profile of \<8.
D: Inclusion Criteria:

* Women in preterm labor between 24 to 32 6/7 weeks' gestation with intact membranes with an age range of 15 to 50 years old.

Exclusion Criteria:

* Cervical dilatation of ≥ 6 cm
* Maternal contraindication to tocolysis
* Known fetal anomalies
* Suspected chorioamnionitis
* Nonreassuring fetal heart tracing
* Vaginal bleeding due to placenta previa or abruptio placenta
* Preterm premature rupture of membranes
* Prolapsed membranes
* Human immunodeficiency virus positive
* Multiple gestation
* Patients on procardia within 24 hours of po intake
* Magnesium sulfate tocolysis prior to randomization
* Patient refusal

Answer: A