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

Neonatal Complications Clinical Trial

— BETADOSE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02897076
• Other study ID #: P150944
• Status: Completed
• Phase: Phase 3
• Start date: January 2017
• Est. completion date: January 5, 2020

Study information

• Verified date: April 2020
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3250
• Est. completion date: January 5, 2020
• Est. primary completion date: January 5, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Neonatal Complications
• Premature Birth

Intervention

Drug:
• betamethasone 24 mg

• 12mg betamethasone +placebo

Locations

Country	Name	City	State
France	Hôpital Robert Debré	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (3)

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. — View Citation

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. — View Citation

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-Dorrie — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	highest appropriate fractional inspired oxygen (FiO2)		48 hours of life
Secondary	maximum appropriate Mean Airway Pressure (MAP)		48 hours of life
Secondary	duration of mechanical ventilation		36 weeks post conception
Secondary	duration of oxygen therapy		36 weeks post conception
Secondary	oxygen therapy		36 weeks post conception
Secondary	neonatal death		36 weeks post conception
Secondary	admission to neonatal intensive care unit		36 weeks post conception
Secondary	inotropic support		36 weeks post conception
Secondary	air leak syndrome		36 weeks post conception
Secondary	patent ductus arteriosus		36 weeks post conception
Secondary	necrotising enterocolitis		36 weeks post conception
Secondary	intraventricular hemorrhage and grade		36 weeks post conception
Secondary	periventricular leukomalacia		36 weeks post conception
Secondary	use of postnatal steroids		36 weeks post conception
Secondary	retinopathy of prematurity		36 weeks post conception
Secondary	length of hospital stay		36 weeks post conception
Secondary	early onset sepsis		36 weeks post conception
Secondary	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.	36 weeks post conception