Preterm BirthPhase 4APOSTEL 8NCT05693688
Atosiban Versus Placebo in the Treatment of Late Threatened Pre-term Birth
A Phase 4 study testing Atosiban in people with Preterm Birth, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Preterm Birth
- What is being tested?
- Atosiban
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 760 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Dec 2017to 29 Feb 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Previous treatment for threatened preterm birth with corticosteroids in current pregnancy
- Contra indication for tocolysis
- Signs of fetal distress
- Signs of intra uterine infection
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Amsterdam University Medical Centres, location AMC
Amsterdam, North Holland, 1105 AZ
About this study
Official title: Atosiban Versus Placebo in the Treatment of Late Threatened Preterm Birth
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.
Read the 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).
- Conditions
- Preterm Birth
- Being tested
- Atosiban
- Keywords
- preterm birth, threatened preterm birth, preterm labour, atosiban, adverse neonatal outcome
- Medical subject headings
- Premature Birth, Obstetric Labor, Premature
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtosibanDrug
Also called Tractocile
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.
| Study group | Role | What they receive |
|---|---|---|
| atosiban | Experimental | 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. Receives: Drug: Atosiban |
| placebo | Placebo comparator | 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. Receives: Drug: Atosiban |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse neonatal outcome
Combination perinatal mortality and severe neonatal morbidity (BPD, NEC, ROP, IVH, PVL, sepsis,
Measured: Up to 3 months corrected age
Secondary outcomes (12)
Birth within 48 hours
Measured: 48 hours
Time to delivery
Measured: Not applicible
Gestational age at delivery
Measured: At birth
Birth weight
Measured: At birth
Mechanical ventilation
Number of days on invasive ventilation
Measured: Up to 3 months corrected age
NICU
Lengt of admission in NICU
Measured: Up to 3 months corrected age
Convulsions
Measured: Up to 3 months corrected age
Asphyxia
Measured: Up to 3 months corrected age
Meningitis
Measured: Up to 3 months corrected age
Pneumothorax
Measured: Up to 3 months corrected age
Maternal infection
Measured: Up to 3 months corrected age
Maternal side effects
Measured: Up to 3 months corrected age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2023
- Study start1 Dec 2017
- Primary completion29 Feb 2024
- Study completion29 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Preterm BirthStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- International, multicenter, double blinded, placebo controlled RCT
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 760 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- 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, Frisius Medisch Centrum, 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
- Responsible party
- Principal investigator, Martijn A. Oudijk, MD, PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05693688
- Sponsor's protocol ID
- NL80-84800-98-41027
- Acronym
- APOSTEL 8
- Status last verified
- Jul 2024
- First submitted
- 12 Jan 2023
- Last updated
- 25 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 31772083
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Atosiban Versus Placebo in the Treatment of Late Threatened Preterm Birth
- ClinicalTrials.gov ID
- NCT05693688
- Acronym / sponsor ID
- APOSTEL 8 / NL80-84800-98-41027
- Conditions
- Preterm Birth
- Keywords
- preterm birth, threatened preterm birth, preterm labour, atosiban, adverse neonatal outcome
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 760 participants (actual)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- 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, Frisius Medisch Centrum, 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
- Study start
- 1 Dec 2017 (actual)
- Primary completion
- 29 Feb 2024 (actual)
- Study completion
- 29 Feb 2024 (actual)
- First posted
- 23 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- International, multicenter, double blinded, placebo controlled RCT
| Arm | Type | Receives |
|---|---|---|
| atosiban | Experimental | Drug: AtosibanAtosiban: 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 | Placebo comparator | Drug: AtosibanPlacebo: 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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:
Key exclusion criteria (4 listed)
- Previous treatment for threatened preterm birth with corticosteroids in current pregnancy
- Contra indication for tocolysis
- Signs of fetal distress
- Signs of intra uterine infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AtosibanAlso: Tractocileatosiban 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. | Drug | atosiban, placebo |
Primary outcome
Adverse neonatal outcome
Time frame: Up to 3 months corrected age
Combination perinatal mortality and severe neonatal morbidity (BPD, NEC, ROP, IVH, PVL, sepsis,
12 secondary outcomes
Birth within 48 hours
Time frame: 48 hours
Time to delivery
Time frame: Not applicible
Gestational age at delivery
Time frame: At birth
Birth weight
Time frame: At birth
Mechanical ventilation
Time frame: Up to 3 months corrected age
NICU
Time frame: Up to 3 months corrected age
Convulsions
Time frame: Up to 3 months corrected age
Asphyxia
Time frame: Up to 3 months corrected age
Meningitis
Time frame: Up to 3 months corrected age
Pneumothorax
Time frame: Up to 3 months corrected age
Maternal infection
Time frame: Up to 3 months corrected age
Maternal side effects
Time frame: Up to 3 months corrected age
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2024.
- Background: PubMed 31772083Klumper 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.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Atosiban in people with Preterm Birth, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse neonatal outcome (time frame: Up to 3 months corrected age). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05693688, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2024.