Neonatal ComplicationsPhase 3BETADOSENCT02897076
Dose Reduction of Antenatal Betamethasone Given to Prevent the Neonatal Complications Associated With Very Preterm Birth
A Phase 3 study testing betamethasone 24 mg in people with Neonatal Complications, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Extensive animal studies have indicated that antenatal betamethasone exposure results in altered developmental trajectories of several fetal systems. Follow up of a randomized controlled trial has shown that antenatal betamethasone exposure might result in insulin resistance 30 years later. Read more about this study
- Who is it for?
- Ages 18 to 60 years, women only
- Conditions the study is for
- Neonatal Complications
- What is being tested?
- betamethasone 24 mg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 3,250 participants
- Where
- 1 siteFrance
- Study dates
- Jan 2017to 5 Jan 2020
- Phase
- Phase 3
- 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 to 60 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Singleton pregnancy
- Patient Having receipt the first injection of betamethasone and pregnancy term < 32 weeks of gestation
- Age > 18 years
- Patient affiliated to a social security regime
Who cannot join
- Chromosomal aberrations and major fetal malformations
- Cervical dilatation ≥ 4 cm and of cervical length ≥20mm.
- Patient who have already received a first course of betamethasone
- first intravenous injection of betamethasone
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Dose Reduction of Antenatal Betamethasone Given to Prevent the Neonatal Complications Associated With Very Preterm Birth: a Randomized, Multicentre, Double Blind Placebo-controlled Non Inferiority Trial
Extensive animal studies have indicated that antenatal betamethasone exposure results in altered developmental trajectories of several fetal systems. Follow up of a randomized controlled trial has shown that antenatal betamethasone exposure might result in insulin resistance 30 years later. Furthermore, animal studies and randomized trials in Humans have clearly demonstrated that betamethasone-induced growth alterations were dose-related.
In ewes, a 50% reduced dose regimen resulted in maximal improvement in preterm lamb lung function, similar to those obtained after a full dose.
Our hypothesis is that antenatal betamethasone after a 50% dose reduction, justified by the potential long term effects of this drug, is not inferior to a full dose to promote fetal lung maturation in Humans.
Read the detailed description
The BETADOSE project consist in a randomized, multicenter, double blind placebo-controlled non inferiority trial comparing a standard dose regimen (24 mg) to a reduced dose regimen (12 mg) of betamethasone given to prevent the neonatal complications associated with very preterm birth.A betamethasone course consists in 2 injections of 12 mg betamethasone 24 hours apart for a total dose of 24 mg.
The first injection will be unmasked in both group. In both group, women will receive a first 12 mg injection of betamethasone according to local protocols.
Randomization will be performed after the first injection. Women will then receive either a placebo injection (reduced dose regimen, 12 mg only from the first injection) or a second 12 mg betamethasone injection (standard dose regimen, 12 mg from the first injection and 12 mg from the second injection=24 mg). This protocol allows women sent from level 1 and 2 to level 3 perinatal centers after having already received their first injection to participate.
In case of multiple antenatal betamethasone courses, women will receive their second course according to the same design as in their first course.
- Conditions
- Neonatal Complications
- Being tested
- betamethasone 24 mg, 12mg betamethasone +placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
betamethasone 24 mgDrug
12mg betamethasone +placeboDrug
| Study group | Role | What they receive |
|---|---|---|
| 12mg betamethasone+12mg betamethasone | Active comparator | A betamethasone course consists in 2 intramuscular injections of 12 mg betamethasone 24 hours apart for a total dose of 24 mg.
In the BETADOSE trial, the first injection will be unmasked in both groups. In both groups, women will received a first 12 mg injection of betamethasone according to local protocols.
Randomization will be performed after the first injection. Women will then received either a blinded placebo injection (50% reduced dose regimen, 12 mg only from the first injection) or a second blinded 12 mg betamethasone injection (standard full dose regimen, 12 mg from the first injection and 12 mg from the second injection=24 mg). Receives: Drug: betamethasone 24 mg |
| 12 mg betamethasone+ placebo | Placebo comparator | A betamethasone course consists in 2 intramuscular injections of 12 mg betamethasone 24 hours apart for a total dose of 24 mg.
In the BETADOSE trial, the first injection will be unmasked in both groups. In both groups, women will received a first 12 mg injection of betamethasone according to local protocols.
Randomization will be performed after the first injection. Women will then received either a blinded placebo injection (50% reduced dose regimen, 12 mg only from the first injection) or a second blinded 12 mg betamethasone injection (standard full dose regimen, 12 mg from the first injection and 12 mg from the second injection=24 mg). Receives: Drug: 12mg betamethasone +placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
severe RDS defined as need for exogenous intra-tracheal surfactant in the first 48 hours of life
The primary assessment criterion is severe respiratory distress syndrome(RDS) defined as need for exogenous intra-tracheal surfactant in the first 48 hours of life. It is considered as a binary endpoint: failure if there is occurrence of RDS, or not failure.
Measured: 48 hours of life
Secondary outcomes (18)
highest appropriate fractional inspired oxygen (FiO2)
Measured: 48 hours of life
maximum appropriate Mean Airway Pressure (MAP)
Measured: 48 hours of life
duration of mechanical ventilation
Measured: 36 weeks post conception
duration of oxygen therapy
Measured: 36 weeks post conception
oxygen therapy
Measured: 36 weeks post conception
neonatal death
Measured: 36 weeks post conception
admission to neonatal intensive care unit
Measured: 36 weeks post conception
inotropic support
Measured: 36 weeks post conception
air leak syndrome
Measured: 36 weeks post conception
patent ductus arteriosus
Measured: 36 weeks post conception
necrotising enterocolitis
Measured: 36 weeks post conception
intraventricular hemorrhage and grade
Measured: 36 weeks post conception
periventricular leukomalacia
Measured: 36 weeks post conception
use of postnatal steroids
Measured: 36 weeks post conception
retinopathy of prematurity
Measured: 36 weeks post conception
length of hospital stay
Measured: 36 weeks post conception
early onset sepsis
Measured: 36 weeks post conception
Composite endpoint of any of the 4 prematurity-induced complications related to the use of betamethasone
Related to betamethasone impact on other prematurity-induced complications, is a composite outcome taking into account multiple clinical events :
neonatal death, severe RDS defined as need for exogenous intra-tracheal surfactant in the first 48 hours of life, intraventricular hemorrhage high grade, and necrotising enterocolitis.
Measured: 36 weeks post conception
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2016 (estimated)
- Study startJan 2017
- Primary completion5 Jan 2020
- Study completion5 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Neonatal ComplicationsStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 3,250 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Schmitz Thomas, PHD, Principal investigator, APHPBaud Olivier, PHD, Study chair, Hôpitaux Universitaires de Genève - Inserm U1141 Hôpital Robert Debré
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02897076
- Sponsor's protocol ID
- P150944
- Acronym
- BETADOSE
- Status last verified
- Apr 2020
- First submitted
- 7 Sep 2016
- Last updated
- 3 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Schmitz T, Alberti C, Ursino M, Baud O, Aupiais C; BETADOSE study group and the GROG (Groupe de Recherche en Gynecologie Obstetrique). Full versus half dose of antenatal betamethasone to prevent severe neonatal respiratory distress syndrome associated with preterm birth: study protocol for a randomised, multicenter, double blind, placebo-controlled, non-inferiority trial (BETADOSE). BMC Pregnancy Childbirth. 2019 Feb 12;19(1):67. doi: 10.1186/s12884-019-2206-x.
PubMed 30755164Aupiais C, Alberti C, Schmitz T, Baud O, Ursino M, Zohar S. A Bayesian non-inferiority approach using experts' margin elicitation - application to the monitoring of safety events. BMC Med Res Methodol. 2019 Sep 18;19(1):187. doi: 10.1186/s12874-019-0826-5.
PubMed 31533631Schmitz T, Doret-Dion M, Sentilhes L, Parant O, Claris O, Renesme L, Abbal J, Girault A, Torchin H, Houllier M, Le Sache N, Vivanti AJ, De Luca D, Winer N, Flamant C, Thuillier C, Boileau P, Blanc J, Brevaut V, Bouet PE, Gascoin G, Beucher G, Datin-Dorriere V, Bounan S, Bolot P, Poncelet C, Alberti C, Ursino M, Aupiais C, Baud O; BETADOSE trial study group; Groupe de Recherche en Obstetrique et Gynecologie. Neonatal outcomes for women at risk of preterm delivery given half dose versus full dose of antenatal betamethasone: a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial. Lancet. 2022 Aug 20;400(10352):592-604. doi: 10.1016/S0140-6736(22)01535-5.
PubMed 35988568
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose Reduction of Antenatal Betamethasone Given to Prevent the Neonatal Complications Associated With Very Preterm Birth: a Randomized, Multicentre, Double Blind Placebo-controlled Non Inferiority Trial
- ClinicalTrials.gov ID
- NCT02897076
- Acronym / sponsor ID
- BETADOSE / P150944
- Conditions
- Neonatal Complications
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3,250 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Jan 2017
- Primary completion
- 5 Jan 2020 (actual)
- Study completion
- 5 Jan 2020 (actual)
- First posted
- 13 Sep 2016 (estimated)
- 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.
Extensive animal studies have indicated that antenatal betamethasone exposure results in altered developmental trajectories of several fetal systems. Follow up of a randomized controlled trial has shown that antenatal betamethasone exposure might result in insulin resistance 30 years later. Furthermore, animal studies and randomized trials in Humans have clearly demonstrated that betamethasone-induced growth alterations were dose-related.
In ewes, a 50% reduced dose regimen resulted in maximal improvement in preterm lamb lung function, similar to those obtained after a full dose.
Our hypothesis is that antenatal betamethasone after a 50% dose reduction, justified by the potential long term effects of this drug, is not inferior to a full dose to promote fetal lung maturation in Humans.
Detailed description
The BETADOSE project consist in a randomized, multicenter, double blind placebo-controlled non inferiority trial comparing a standard dose regimen (24 mg) to a reduced dose regimen (12 mg) of betamethasone given to prevent the neonatal complications associated with very preterm birth.A betamethasone course consists in 2 injections of 12 mg betamethasone 24 hours apart for a total dose of 24 mg.
The first injection will be unmasked in both group. In both group, women will receive a first 12 mg injection of betamethasone according to local protocols.
Randomization will be performed after the first injection. Women will then receive either a placebo injection (reduced dose regimen, 12 mg only from the first injection) or a second 12 mg betamethasone injection (standard dose regimen, 12 mg from the first injection and 12 mg from the second injection=24 mg). This protocol allows women sent from level 1 and 2 to level 3 perinatal centers after having already received their first injection to participate.
In case of multiple antenatal betamethasone courses, women will receive their second course according to the same design as in their first course.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 12mg betamethasone+12mg betamethasone | Active comparator | Drug: betamethasone 24 mgA betamethasone course consists in 2 intramuscular injections of 12 mg betamethasone 24 hours apart for a total dose of 24 mg. In the BETADOSE trial, the first injection will be unmasked in both groups. In both groups, women will received a first 12 mg injection of betamethasone according to local protocols. Randomization will be performed after the first injection. Women will then received either a blinded placebo injection (50% reduced dose regimen, 12 mg only from the first injection) or a second blinded 12 mg betamethasone injection (standard full dose regimen, 12 mg from the first injection and 12 mg from the second injection=24 mg). |
| 12 mg betamethasone+ placebo | Placebo comparator | Drug: 12mg betamethasone +placeboA betamethasone course consists in 2 intramuscular injections of 12 mg betamethasone 24 hours apart for a total dose of 24 mg. In the BETADOSE trial, the first injection will be unmasked in both groups. In both groups, women will received a first 12 mg injection of betamethasone according to local protocols. Randomization will be performed after the first injection. Women will then received either a blinded placebo injection (50% reduced dose regimen, 12 mg only from the first injection) or a second blinded 12 mg betamethasone injection (standard full dose regimen, 12 mg from the first injection and 12 mg from the second injection=24 mg). |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Singleton pregnancy
- Patient Having receipt the first injection of betamethasone and pregnancy term < 32 weeks of gestation
- Age > 18 years
- Patient affiliated to a social security regime
Key exclusion criteria (4 listed)
- Chromosomal aberrations and major fetal malformations
- Cervical dilatation ≥ 4 cm and of cervical length ≥20mm.
- Patient who have already received a first course of betamethasone
- first intravenous injection of betamethasone
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 |
|---|---|---|
| betamethasone 24 mg | Drug | 12mg betamethasone+12mg betamethasone |
| 12mg betamethasone +placebo | Drug | 12 mg betamethasone+ placebo |
Primary outcome
severe RDS defined as need for exogenous intra-tracheal surfactant in the first 48 hours of life
Time frame: 48 hours of life
The primary assessment criterion is severe respiratory distress syndrome(RDS) defined as need for exogenous intra-tracheal surfactant in the first 48 hours of life. It is considered as a binary endpoint: failure if there is occurrence of RDS, or not failure.
18 secondary outcomes
highest appropriate fractional inspired oxygen (FiO2)
Time frame: 48 hours of life
maximum appropriate Mean Airway Pressure (MAP)
Time frame: 48 hours of life
duration of mechanical ventilation
Time frame: 36 weeks post conception
duration of oxygen therapy
Time frame: 36 weeks post conception
oxygen therapy
Time frame: 36 weeks post conception
neonatal death
Time frame: 36 weeks post conception
admission to neonatal intensive care unit
Time frame: 36 weeks post conception
inotropic support
Time frame: 36 weeks post conception
air leak syndrome
Time frame: 36 weeks post conception
patent ductus arteriosus
Time frame: 36 weeks post conception
necrotising enterocolitis
Time frame: 36 weeks post conception
intraventricular hemorrhage and grade
Time frame: 36 weeks post conception
periventricular leukomalacia
Time frame: 36 weeks post conception
use of postnatal steroids
Time frame: 36 weeks post conception
retinopathy of prematurity
Time frame: 36 weeks post conception
length of hospital stay
Time frame: 36 weeks post conception
early onset sepsis
Time frame: 36 weeks post conception
Composite endpoint of any of the 4 prematurity-induced complications related to the use of betamethasone
Time frame: 36 weeks post conception
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 3 Feb 2023.
- Background: PubMed 30755164Schmitz T, Alberti C, Ursino M, Baud O, Aupiais C; BETADOSE study group and the GROG (Groupe de Recherche en Gynecologie Obstetrique). Full versus half dose of antenatal betamethasone to prevent severe neonatal respiratory distress syndrome associated with preterm birth: study protocol for a randomised, multicenter, double blind, placebo-controlled, non-inferiority trial (BETADOSE). BMC Pregnancy Childbirth. 2019 Feb 12;19(1):67. doi: 10.1186/s12884-019-2206-x.
- Background: PubMed 31533631Aupiais C, Alberti C, Schmitz T, Baud O, Ursino M, Zohar S. A Bayesian non-inferiority approach using experts' margin elicitation - application to the monitoring of safety events. BMC Med Res Methodol. 2019 Sep 18;19(1):187. doi: 10.1186/s12874-019-0826-5.
- Results publication: PubMed 35988568Schmitz T, Doret-Dion M, Sentilhes L, Parant O, Claris O, Renesme L, Abbal J, Girault A, Torchin H, Houllier M, Le Sache N, Vivanti AJ, De Luca D, Winer N, Flamant C, Thuillier C, Boileau P, Blanc J, Brevaut V, Bouet PE, Gascoin G, Beucher G, Datin-Dorriere V, Bounan S, Bolot P, Poncelet C, Alberti C, Ursino M, Aupiais C, Baud O; BETADOSE trial study group; Groupe de Recherche en Obstetrique et Gynecologie. Neonatal outcomes for women at risk of preterm delivery given half dose versus full dose of antenatal betamethasone: a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial. Lancet. 2022 Aug 20;400(10352):592-604. doi: 10.1016/S0140-6736(22)01535-5.
- Individual participant dataSharing planned: No
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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.
Schmitz Thomas, PHD principal investigator
APHP
Baud Olivier, PHD study chair
Hôpitaux Universitaires de Genève - Inserm U1141 Hôpital Robert Debré
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing betamethasone 24 mg in people with Neonatal Complications, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 4 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 3 Feb 2023. 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 France. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
severe RDS defined as need for exogenous intra-tracheal surfactant in the first 48 hours of life (time frame: 48 hours of life). 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 NCT02897076, which also lists 3 linked publications.
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 3 Feb 2023.