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Progestagens for the Tertiary Prophylaxis of Preterm Delivery

Phase 3
Completed
Conditions
Preterm Delivery
Neonatal Complications
Interventions
Drug: 17 alpha-hydroxy progesterone caproate
Procedure: Control
Registration Number
NCT01178788
Lead Sponsor
University of Modena and Reggio Emilia
Brief Summary

Objective: This trial would evaluate the clinical effectiveness of Progesterone(P) and 17-hydroxy Progesterone (17P) in reducing PTD, in symptomatic women at risk because of cervical shortening, in the present pregnancy.

Main outcome: Delivery before 37 weeks.

Secondary outcomes: Gestational age at delivery, Delivery \<32, \<35 wks, hospital admissions before delivery, birth-weight centile, NICU admission, days of NICU admission, days of oxygen supply, composite neonatal complications, congenital neonatal malformations and anomalies.

Allocated treatments will be:

Group A: 17P 341 mg i.m./weekly (Lentogest, AMSA, Italy); Group B: micronized P 200 mg per vagina /day (Utrogestan, Besins Healthcare, Belgium) Group C: no treatment, clinical observation

Concomitant treatments: Iron and folic acid supplementation, and Betamethasone (12 mg repeated once 24 hours apart) will be permitted. Is not allowed the treatment with tocolytics per os. Any treatment will be recorded.

Duration: The period of enrollment is 15 months. Cases not randomized by a clinical unit will be competitively assigned later. Results are expected 20-24 months from starting.

Sample Size: hypothesizing a risk of PTD = 0.30 efficacy is defined as a reduction to 50% (risk = 0.15). With a test potency = 0.80 and alpha = 0.025 study needs to enrol 160 patients/arm, with a total of 480 patients.

Data analysis: Methodological Unit will assign randomized treatment through a web site and it will collect data through the same way.

Detailed Description

Background: According to the last reviews Progesterone (P) and (17P) are able to reduce preterm delivery (PTD), either as prophylactic administration in the presence of previous PTD or as a treatment of the actual pregnancy, becoming at risk because of cervical shortening/preterm labour. At present is difficult to distinguish the clinical effects of P from the one of 17P as well as it is impossible to choice among the diverse doses and formulations utilized in the RCTs published so far, as well as in those under recruitment.

Protocol: Women will be treated with P, 17P or just clinically observed according to on-line randomization assignment provided by the Methodological Unit. Treatments end at the completion of 36th week. Randomization will be stratified for early (22-27+6th) and late (28-31+6th wks) PTD risk. Interim analysis will be done at 50% enrollment.

Sixty women will be allocated to each Clinical Centre to reach 480 enrollments, in the 3 arms.

Drugs will be provided by manufacturers.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
254
Inclusion Criteria
  • Women with singleton pregnancy at 22+0nd to 31+6nd week of gestation presenting with a cervical length ≤25 mm, after an episode of preterm labour.
Exclusion Criteria
  • Women with previous spontaneous PTD, multiple pregnancy, rupture of membranes, feto-maternal conditions indicating delivery, mullerian malformations, cervical surgery (cervical cerclage etc), presence of regular uterine contractions

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
17 alfa hydroxy Progesterone caproate17 alpha-hydroxy progesterone caproateWomen treated with i.m. 17P injection/weekly (Lentogest, IBSA, Italy)
ControlControlRoutine clinical controls
Micronized Progesteronemicronized Progesteronemicronized P 200 mg per vagina /day (Utrogestan, Besins Healthcare, Belgium)
Primary Outcome Measures
NameTimeMethod
Preterm delivery (37 weeks of gestation)6 mo. after end of recruitment
Secondary Outcome Measures
NameTimeMethod
Delivery <32, <35 wks6 months after the end of the study
Hospital admissions before delivery6 months after the end of the study
Gestational age at delivery6 months after the end of the study
congenital neonatal anomalies6 months after the end of the study
Birth-weight centile6 months after the end of the study
NICU admission6 months after the end of the study
days of NICU admission6 months after the end of the study
days of oxygen supply6 months after the end of the study
congenital neonatal malformations6 months after the end of the study
composite neonatal complications6 months after the end of the study

Include: RDS, IVH, ROP, PVL, NEC, Sepsis

Trial Locations

Locations (1)

University of Modena and Reggio Emilia

🇮🇹

Modena, Italy

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