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Atosiban Versus Placebo in the Treatment of Late Threatened Pre-term Birth (APOSTEL 8)

Primary Purpose

Preterm Birth

Status
Recruiting
Phase
Phase 4
Locations
Netherlands
Study Type
Interventional
Intervention
Atosiban
Sponsored by
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Preterm Birth focused on measuring preterm birth, threatened preterm birth, preterm labour, atosiban, adverse neonatal outcome

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleAccepts Healthy Volunteers

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

Sites / Locations

  • Amsterdam University Medical Centres, location AMCRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

atosiban

placebo

Arm Description

Atosiban: bolus injection of 6.75 mg/0.9 ml atosiban in one minute followed by a continuous infusion of 18 mg/hour (=24ml/hour) for 3 hours followed by a continuous infusion of 6 mg/hour (=8 ml/hour) for the remaining 45 hours.

Placebo: injection of 0.9 ml saline in one minute followed by a saline infusion for 3 hours (24 ml/hour) followed by a continuous infusion (8 ml/hour) for the remaining 45 hours.

Outcomes

Primary Outcome Measures

Adverse neonatal outcome
Combination perinatal mortality and severe neonatal morbidity (BPD, NEC, ROP, IVH, PVL, sepsis,

Secondary Outcome Measures

Birth within 48 hours
Time to delivery
Gestational age at delivery
Birth weight
Mechanical ventilation
Number of days on invasive ventilation
NICU
Lengt of admission in NICU
Convulsions
Asphyxia
Meningitis
Pneumothorax
Maternal infection
Maternal side effects

Full Information

First Posted
January 12, 2023
Last Updated
January 31, 2023
Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborators
ZonMw: The Netherlands Organisation for Health Research and Development, Nottingham University Hospitals NHS Trust, Amphia Hospital, St. Antonius Hospital, Deventer Ziekenhuis, Erasmus Medical Center, Flevoziekenhuis, Franciscus Gasthuis, Gelre Hospitals, Groene Hart Ziekenhuis, Isala, Leiden University Medical Center, Martini Hospital Groningen, Maxima Medical Center, Medical Centre Leeuwarden, Haaglanden Medical Centre, Maastricht University Medical Center, Medisch Spectrum Twente, OLVG, Radboud University Medical Center, Rijnstate Hospital, Spaarne Gasthuis, Tergooi Hospital, University Medical Center Groningen, UMC Utrecht, Diakonessenhuis, Utrecht, Ziekenhuisgroep Twente, Zuyderland Medical Centre, National Maternity Hospital, Ireland
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1. Study Identification

Unique Protocol Identification Number
NCT05693688
Brief Title
Atosiban Versus Placebo in the Treatment of Late Threatened Pre-term Birth
Acronym
APOSTEL 8
Official Title
Atosiban Versus Placebo in the Treatment of Late Threatened Preterm Birth
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 1, 2017 (Actual)
Primary Completion Date
July 2023 (Anticipated)
Study Completion Date
July 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborators
ZonMw: The Netherlands Organisation for Health Research and Development, Nottingham University Hospitals NHS Trust, Amphia Hospital, St. Antonius Hospital, Deventer Ziekenhuis, Erasmus Medical Center, Flevoziekenhuis, Franciscus Gasthuis, Gelre Hospitals, Groene Hart Ziekenhuis, Isala, Leiden University Medical Center, Martini Hospital Groningen, Maxima Medical Center, Medical Centre Leeuwarden, Haaglanden Medical Centre, Maastricht University Medical Center, Medisch Spectrum Twente, OLVG, Radboud University Medical Center, Rijnstate Hospital, Spaarne Gasthuis, Tergooi Hospital, University Medical Center Groningen, UMC Utrecht, Diakonessenhuis, Utrecht, Ziekenhuisgroep Twente, Zuyderland Medical Centre, National Maternity Hospital, Ireland

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Preterm Birth
Keywords
preterm birth, threatened preterm birth, preterm labour, atosiban, adverse neonatal outcome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
International, multicenter, double blinded, placebo controlled RCT
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double blinded
Allocation
Randomized
Enrollment
760 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
atosiban
Arm Type
Experimental
Arm Description
Atosiban: bolus injection of 6.75 mg/0.9 ml atosiban in one minute followed by a continuous infusion of 18 mg/hour (=24ml/hour) for 3 hours followed by a continuous infusion of 6 mg/hour (=8 ml/hour) for the remaining 45 hours.
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
Placebo: injection of 0.9 ml saline in one minute followed by a saline infusion for 3 hours (24 ml/hour) followed by a continuous infusion (8 ml/hour) for the remaining 45 hours.
Intervention Type
Drug
Intervention Name(s)
Atosiban
Other Intervention Name(s)
Tractocile
Intervention Description
atosiban i.v. administred for 48 hours. The medication will be administered by a bolus injection of 6.75 mg/0.9 mL in 1 min followed by a continuous infusion of 18 mg/hour for 3 hours followed by a continuous infusion of 6 mg/hour for the remaining 45 hours.
Primary Outcome Measure Information:
Title
Adverse neonatal outcome
Description
Combination perinatal mortality and severe neonatal morbidity (BPD, NEC, ROP, IVH, PVL, sepsis,
Time Frame
Up to 3 months corrected age
Secondary Outcome Measure Information:
Title
Birth within 48 hours
Time Frame
48 hours
Title
Time to delivery
Time Frame
Not applicible
Title
Gestational age at delivery
Time Frame
At birth
Title
Birth weight
Time Frame
At birth
Title
Mechanical ventilation
Description
Number of days on invasive ventilation
Time Frame
Up to 3 months corrected age
Title
NICU
Description
Lengt of admission in NICU
Time Frame
Up to 3 months corrected age
Title
Convulsions
Time Frame
Up to 3 months corrected age
Title
Asphyxia
Time Frame
Up to 3 months corrected age
Title
Meningitis
Time Frame
Up to 3 months corrected age
Title
Pneumothorax
Time Frame
Up to 3 months corrected age
Title
Maternal infection
Time Frame
Up to 3 months corrected age
Title
Maternal side effects
Time Frame
Up to 3 months corrected age
Other Pre-specified Outcome Measures:
Title
Costs
Time Frame
Up to 3 months corrected age

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Larissa van der Windt, MD
Phone
+31 6 42939524
Email
apostel8@amsterdamumc.nl
Facility Information:
Facility Name
Amsterdam University Medical Centres, location AMC
City
Amsterdam
State/Province
Noord-Holland
ZIP/Postal Code
1105 AZ
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Larissa van der Windt, MD
Phone
31 6 42939524
Email
apostel8@amsterdamumc.nl
First Name & Middle Initial & Last Name & Degree
Martijn A Oudijk, MD, PhD, Prof
Email
m.a.oudijk@amsterdamumc.nl
First Name & Middle Initial & Last Name & Degree
Martijn A Oudijk, MD, PhD
First Name & Middle Initial & Last Name & Degree
Carolien Dijkstra-Roos, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
31772083
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. Erratum In: BMJ Open. 2022 Oct 21;12(10):e029101corr1.
Results Reference
background
Links:
URL
https://zorgevaluatienederland.nl/evaluations/apostel8
Description
Related Info

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Atosiban Versus Placebo in the Treatment of Late Threatened Pre-term Birth

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