Dose Reduction of Antenatal Betamethasone Given to Prevent the Neonatal Complications Associated With Very Preterm Birth

NCT ID: NCT02897076

Last Updated: 2023-02-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 3250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-31
• Study Completion Date: 2020-01-05

Brief 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. 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.

Conditions

Neonatal Complications

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

12mg betamethasone+12mg betamethasone

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).

Group Type: ACTIVE_COMPARATOR

betamethasone 24 mg

Intervention Type: DRUG

12 mg betamethasone+ placebo

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).

Group Type: PLACEBO_COMPARATOR

12mg betamethasone +placebo

Intervention Type: DRUG

Interventions

betamethasone 24 mg

Intervention Type: DRUG

12mg betamethasone +placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Schmitz Thomas, PHD

Role: PRINCIPAL_INVESTIGATOR

APHP

Baud Olivier, PHD

Role: STUDY_CHAIR

Hôpitaux Universitaires de Genève - Inserm U1141 Hôpital Robert Debré

Locations

Hôpital Robert Debré

Paris, , France

Countries

France

References

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.

Reference Type: BACKGROUND

PMID: 30755164 (View on PubMed)

Aupiais 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.

Reference Type: BACKGROUND

PMID: 31533631 (View on PubMed)

Schmitz 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.

Reference Type: RESULT

PMID: 35988568 (View on PubMed)

Other Identifiers

P150944

Identifier Type: -

Identifier Source: org_study_id