Clinical trial NCT00331695: Efficacy of 17 Alpha-hydroxyprogesterones Caproate for the Prevention of Preterm Delivery
Official title: Evaluation of the Efficacy of 17 Alpha-hydroxyprogesterones Caproate for the Prevention of Preterm Delivery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Preterm Delivery
Keywords: Progesterone
Preterm delivery
Preterm labor
Cervical length
ultrasonography
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2006-05-31
Enrollment: 560
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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

Eligibility criteria: 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.

Primary outcomes:
measure: Interval between inclusion and delivery.
timeFrame: during de study
Secondary outcomes:
measure: Preterm delivery rate < 37 W, < 34 W et < 32 W,
timeFrame: during the study
measure: Number of hospitalizations for preterm labor,
timeFrame: during the study
measure: Cerclage performed at or after 20 weeks,
timeFrame: during the study
measure: Neonatal weight,
timeFrame: during the study
measure: NICU transport
timeFrame: during the study
measure: Respiratory distress syndrome,
timeFrame: during the study
measure: Bronchopulmonary dysplasia,
timeFrame: during the study
measure: Necrotizing enterocolitis,
timeFrame: during the study
measure: leucomalacia,
timeFrame: during the study
measure: neonatal death.
timeFrame: during the study
Other outcomes:
Locations:
city: Poissy
country: France
facility: CHI Poissy st Germain
city: Poissy
country: France
facility: Chi Poissy St Germain
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Patrick ROZENBERG, MD,
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rozenberg P, Rudant J, Chevret S, Boulogne AI, Ville Y. Repeat measurement of cervical length after successful tocolysis. Obstet Gynecol. 2004 Nov;104(5 Pt 1):995-9. doi: 10.1097/01.AOG.0000143254.27255.e9.
citation: Winer N, Bretelle F, Senat MV, Bohec C, Deruelle P, Perrotin F, Connan L, Vayssiere C, Langer B, Capelle M, Azimi S, Porcher R, Rozenberg P; Groupe de Recherche en Obstetrique et Gynecologie. 17 alpha-hydroxyprogesterone caproate does not prolong pregnancy or reduce the rate of preterm birth in women at high risk for preterm delivery and a short cervix: a randomized controlled trial. Am J Obstet Gynecol. 2015 Apr;212(4):485.e1-485.e10. doi: 10.1016/j.ajog.2014.10.1097. Epub 2014 Oct 30.