Clinical trial NCT05693688: Atosiban Versus Placebo in the Treatment of Late Threatened Pre-term Birth
Official title: Atosiban Versus Placebo in the Treatment of Late Threatened Preterm Birth
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Preterm Birth
Keywords: preterm birth
threatened preterm birth
preterm labour
atosiban
adverse neonatal outcome
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
name: Nottingham University Hospitals NHS Trust
name: Amphia Hospital
name: St. Antonius Hospital
name: Deventer Ziekenhuis
name: Erasmus Medical Center
name: Flevoziekenhuis
name: Franciscus Gasthuis
name: Gelre Hospitals
name: Groene Hart Ziekenhuis
name: Isala
name: Leiden University Medical Center
name: Martini Hospital Groningen
name: Maxima Medical Center
name: Frisius Medisch Centrum
name: Haaglanden Medical Centre
name: Maastricht University Medical Center
name: Medisch Spectrum Twente
name: OLVG
name: Radboud University Medical Center
name: Rijnstate Hospital
name: Spaarne Gasthuis
name: Tergooi Hospital
name: University Medical Center Groningen
name: UMC Utrecht
name: Diakonessenhuis, Utrecht
name: Ziekenhuisgroep Twente
name: Zuyderland Medical Centre
name: National Maternity Hospital, Ireland
First posted: 2023-01-23
Enrollment: 760
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: International, multicenter, double blinded, placebo controlled RCT
Primary purpose: TREATMENT

Brief summary: The aim of this study is to investigate if tocolysis with atosiban in late preterm birth (30 to 34 weeks) is (cost-) effective compared with placebo in improving neonatal morbidity and mortality.

Detailed description: Research question Does tocolysis with atosiban reduce neonatal mortality and mortality in women with threatened preterm birth between 30 and 34 weeks when compared to placebo?

Study design Multicenter, double blinded, placebo controlled RCT

Study population Women with threatened preterm birth between 30 and 34 weeks of gestation are eligible for the trial. More than 20 hospitals (including all 10 perinatal centres) in the Netherlands will participate in this trial, as well as 15 hospitals in the UK and 1 in Dublin, Ireland.

Threatened preterm birth is defined as listed below in the inclusion criteria. Our previous APOSTEL III study showed that half of the women with these criteria deliver within seven days, validating this definition of women at high risk for preterm birth.

Inclusion criteria

* Women ≥ 18 years old
* Singleton or twin pregnancy
* Gestational age between 30 0/7 and 33 6/7 weeks
* Threatened preterm birth defined by regular uterine contractions, AND one of the following:

  * Cervical length of \< 15 mm OR
  * Cervical length of 15-30 mm and a positive Fibronectine test (≥ 50 ng/mL) OR
  * In case of absence of cervical length measurement in local protocol a positive Fibronectin test or Partus test OR
  * Ruptured amniotic membranes

Exclusion criteria

* Previous treatment for threatened preterm birth with corticosteroids.
* Contra-indication for tocolysis
* Signs of fetal distress
* Signs of intra uterine infection

Participants RCT: 760 (380 per group)

Description of intervention(s) Tocolysis with atosiban versus placebo.

Outcome measures The primary outcome is a combined perinatal outcome of severe neonatal morbidity and perinatal mortality Secondary outcomes will be birth within 48 hours, time to delivery, gestational age at delivery, birth weight, number of days on invasive mechanical ventilation, length of admission in NICU, convulsions, asphyxia, meningitis, pneumothorax and mortality until 3 months corrected age, maternal infection, maternal side effects and costs.

All outcomes are in the electronic patient file. No additional tests are required for mother or baby.

Power / data analysis Based on the APOSTEL 3 data, the proportion of adverse perinatal outcome in women randomized between 30 and 34 weeks gestation and treated with atosiban was 6%. Based on two recent studies, we expect a 49,8% reduction of 11,95% adverse perinatal outcome in the placebo group to 6% in the atosiban group. Therefore we need to randomize 722 women (beta-error 0.2; alpha error 0.05). Assuming a 5% drop-out rate, we need to randomize 760 women (380 in each arm).

Eligibility criteria: Inclusion Criteria:

* Women ≥ 18 years
* Singleton or twin pregnancy
* Gestational age between 30 0/7 and 33 6/7 weeks
* Threatened preterm birth defined by regular uterine contractions, AND one of the following:

  * Cervical length of \< 15 mm OR
  * Cervical length of 15-30 mm and a positive Fibronectine test (≥ 50 ng/mL) OR
  * In case of absence of cervical length measurement in local protocol a positive Fibronectin test or Partus test OR
  * Ruptured amniotic membranes

Exclusion Criteria:

* Previous treatment for threatened preterm birth with corticosteroids in current pregnancy
* Contra indication for tocolysis
* Signs of fetal distress
* Signs of intra uterine infection

Primary outcomes:
measure: Adverse neonatal outcome
timeFrame: Up to 3 months corrected age
Secondary outcomes:
measure: Birth within 48 hours
timeFrame: 48 hours
measure: Time to delivery
timeFrame: Not applicible
measure: Gestational age at delivery
timeFrame: At birth
measure: Birth weight
timeFrame: At birth
measure: Mechanical ventilation
timeFrame: Up to 3 months corrected age
measure: NICU
timeFrame: Up to 3 months corrected age
measure: Convulsions
timeFrame: Up to 3 months corrected age
measure: Asphyxia
timeFrame: Up to 3 months corrected age
measure: Meningitis
timeFrame: Up to 3 months corrected age
measure: Pneumothorax
timeFrame: Up to 3 months corrected age
measure: Maternal infection
timeFrame: Up to 3 months corrected age
measure: Maternal side effects
timeFrame: Up to 3 months corrected age
Other outcomes:
measure: Costs
timeFrame: Up to 3 months corrected age
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam University Medical Centres, location AMC
state: Noord-Holland
Study officials:
References:
citation: Klumper J, Breebaart W, Roos C, Naaktgeboren CA, van der Post J, Bosmans J, van Kaam A, Schuit E, Mol BW, Baalman J, McAuliffe F, Thornton J, Kok M, Oudijk MA. Study protocol for a randomised trial for atosiban versus placebo in threatened preterm birth: the APOSTEL 8 study. BMJ Open. 2019 Nov 26;9(11):e029101. doi: 10.1136/bmjopen-2019-029101.