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

NCT02897076 | Completed Phase 3

• 1 other identifier: P150944
• Study Type: interventional
• Target: 3,250
• Locations: 1 country
• Sites: 1

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.

Conditions

Neonatal Complications

Outcome Measures

Primary Outcomes (1)

• 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.

  48 hours of life

Secondary Outcomes (18)

• highest appropriate fractional inspired oxygen (FiO2)

  48 hours of life

• maximum appropriate Mean Airway Pressure (MAP)

  48 hours of life

• duration of mechanical ventilation

  36 weeks post conception

• duration of oxygen therapy

  36 weeks post conception

• oxygen therapy

  36 weeks post conception

Study Arms (2)

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).

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).

Drug: 12mg betamethasone +placebo

Interventions

betamethasone 24 mg DRUG

12mg betamethasone+12mg betamethasone

12mg betamethasone +placebo DRUG

12 mg betamethasone+ placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hôpital Robert Debré

Paris, 75019, France

Location

Related Publications (3)

• 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.

  PMID: 30755164 BACKGROUND

• 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.

  PMID: 31533631 BACKGROUND

• 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.

  PMID: 35988568 RESULT

MeSH Terms

Interventions

Betamethasone

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Schmitz Thomas, PHD

  APHP

  PRINCIPAL INVESTIGATOR

• Baud Olivier, PHD

  Hôpitaux Universitaires de Genève - Inserm U1141 Hôpital Robert Debré

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2016
• First Posted: September 13, 2016
• Study Start: January 1, 2017
• Primary Completion: January 5, 2020
• Study Completion: January 5, 2020
• Last Updated: February 3, 2023

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)