Progestagens for the Tertiary Prophylaxis of Preterm Delivery
Progestagens for the Tertiary Prophylaxis of Preterm Delivery
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.
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.
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