Efficacy of 17 Alpha-hydroxyprogesterones Caproate for the Prevention of Preterm Delivery

• Preterm delivery rate < 37 W, < 34 W et < 32 W, [ Time Frame: during the study ] [ Designated as safety issue: Yes ]
  Preterm delivery rate < 37 W, < 34 W et < 32 W,
• Number of hospitalizations for preterm labor, [ Time Frame: during the study ] [ Designated as safety issue: Yes ]
  Number of hospitalizations for preterm labor,
• Cerclage performed at or after 20 weeks, [ Time Frame: during the study ] [ Designated as safety issue: Yes ]
  Cerclage performed at or after 20 weeks,
• Neonatal weight, [ Time Frame: during the study ] [ Designated as safety issue: Yes ]
  Neonatal weight,
• NICU transport [ Time Frame: during the study ] [ Designated as safety issue: Yes ]
  NICU transport
• Respiratory distress syndrome, [ Time Frame: during the study ] [ Designated as safety issue: Yes ]
  Respiratory distress syndrome,
• Bronchopulmonary dysplasia, [ Time Frame: during the study ] [ Designated as safety issue: Yes ]
  Bronchopulmonary dysplasia,
• Necrotizing enterocolitis, [ Time Frame: during the study ] [ Designated as safety issue: Yes ]
  Necrotizing enterocolitis,
• leucomalacia, [ Time Frame: during the study ] [ Designated as safety issue: Yes ]
  leucomalacia,
• neonatal death. [ Time Frame: during the study ] [ Designated as safety issue: Yes ]
  neonatal death.

• Preterm delivery rate < 37 W, < 34 W et < 32 W,
• Number of hospitalizations for preterm labor,
• Cerclage performed at or after 20 weeks,
• Neonatal weight,
• NICU transport
• Respiratory distress syndrome,
• Bronchopulmonary dysplasia,
• Necrotizing enterocolitis,
• leucomalacia,
• neonatal death.

To demonstrate that the intramuscular administration of 17 alpha hydroxyprogesterones caproate allows to reduce the risk of preterm delivery, in 3 high risk populations defined by the association of an ultrasonographic cervical length egal and inferiority 26 mm between 20 and 32 weeks of gestation and:

• either a first episode of preterm labor stopped by acute tocolysis;
• either a history of late miscarriage or premature delivery or uterine malformation or DES
• either a twin pregnancy. Therefore, a randomised, multicentre trial has been designed with initial stratification according to these three risk groups, opened with two parallel arms.

Objective

To demonstrate that the intramuscular administration of 17 alpha - hydroxyprogesterones caproate allows to reduce the risk of preterm delivery, in 3 high risk populations defined by the association of an ultrasonographic cervical length 26 mm between 20 and 32 weeks of gestation and:

• either a first episode of preterm labor stopped by acute tocolysis;
• either a history of late miscarriage or premature delivery or uterine malformation or DES
• either a twin pregnancy. Experimental design Prospective, randomized, multicenter, trial with initial stratification according to three risk groups, opened with two parallel arms.

The maximal duration for treatment will be 16 weeks for each included patient. The duration for inclusions will be 30 months. The duration for participation of each patient will be 10 to 22 weeks. The foreseen inclusion period for this trial is from 06/01/2006 to 12/31/2008 Description Two therapeutic strategies will be compared in each risk group and attributed by uniform randomisation.

Arm A :IM injection of 17 alpha hydroxyprogesterones caproate, 500 mg, twice a week until 36 W or until preterm delivery in high risk symptomatic group and high risk twin pregnancies group.

IM injection of 17 alpha-hydroxyprogesterones caproate, 500 mg, once a week until 36 W or until preterm delivery in high risk asymptomatic group.

Arm B :No treatment with 17 alpha-hydroxyprogesterones caproate. (usual management) Presentation : Progesterone retard Pharlon 500 mg Tolerance criteria

• nausea,vomiting,
• weakness

Inclusion Criteria:

• ultrasonographic cervical length 26 mm between 20 and 32 weeks of gestation and:
• either a first episode of preterm labor stopped by acute tocolysis
• either a history of late miscarriage or premature delivery or uterine malformation or DES;
• either a twin pregnancy.

Exclusion Criteria:

• cervical dilatation > 3 cm,
• chorioamnionitis,
• fetal distress,
• placenta praevia,
• abruptio placenta,
• preterm premature rupture of membranes,
• polyhydramnios,
• Twin-twin transfusion syndrome,
• IUGR,
• preeclampsia or hypertension,
• other pathology justifying a preterm delivery,
• epilepsy drugs
• participation to another therapeutic trial,
• any patient for whom informed consent cannot be obtained.