Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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). |
|
| 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| betamethasone 24 mg | Drug |
| ||
| 12mg betamethasone +placebo |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| highest appropriate fractional inspired oxygen (FiO2) | 48 hours of life | |
| maximum appropriate Mean Airway Pressure (MAP) | 48 hours of life | |
| duration of mechanical ventilation |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Schmitz Thomas, PHD | APHP | Principal Investigator |
| Baud Olivier, PHD | Hôpitaux Universitaires de Genève - Inserm U1141 Hôpital Robert Debré | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hôpital Robert Debré | Paris | 75019 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30755164 | Background | 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. | |
| 31533631 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D001623 | Betamethasone |
| ID | Term |
|---|---|
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Drug |
|
| 36 weeks post conception |
| duration of oxygen therapy | 36 weeks post conception |
| oxygen therapy | 36 weeks post conception |
| neonatal death | 36 weeks post conception |
| admission to neonatal intensive care unit | 36 weeks post conception |
| inotropic support | 36 weeks post conception |
| air leak syndrome | 36 weeks post conception |
| patent ductus arteriosus | 36 weeks post conception |
| necrotising enterocolitis | 36 weeks post conception |
| intraventricular hemorrhage and grade | 36 weeks post conception |
| periventricular leukomalacia | 36 weeks post conception |
| use of postnatal steroids | 36 weeks post conception |
| retinopathy of prematurity | 36 weeks post conception |
| length of hospital stay | 36 weeks post conception |
| early onset sepsis | 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. | 36 weeks post conception |
| 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. |
| 35988568 | Result | 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. |
| D000072473 |
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |