Clinical trial NCT01178788: Progestagens for the Tertiary Prophylaxis of Preterm Delivery
Official title: Progestagens for the Tertiary Prophylaxis of Preterm Delivery in Women With Short Cervix. A Randomized Multicentre Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Preterm Delivery
Neonatal Complications
Keywords: Progestagens
Tertiary Prophylaxis
Micronized Progesterone
17 alpha hydroxy P
Preterm Delivery
Cervical shortening
Lead sponsor: University of Modena and Reggio Emilia
Sponsor class: OTHER
First posted: 2010-08-10
Enrollment: 254
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Preterm delivery (37 weeks of gestation)
timeFrame: 6 mo. after end of recruitment
Secondary outcomes:
measure: Delivery <32, <35 wks
timeFrame: 6 months after the end of the study
measure: Hospital admissions before delivery
timeFrame: 6 months after the end of the study
measure: Gestational age at delivery
timeFrame: 6 months after the end of the study
measure: Birth-weight centile
timeFrame: 6 months after the end of the study
measure: NICU admission
timeFrame: 6 months after the end of the study
measure: days of NICU admission
timeFrame: 6 months after the end of the study
measure: days of oxygen supply
timeFrame: 6 months after the end of the study
measure: composite neonatal complications
timeFrame: 6 months after the end of the study
measure: congenital neonatal anomalies
timeFrame: 6 months after the end of the study
measure: congenital neonatal malformations
timeFrame: 6 months after the end of the study
Other outcomes:
Locations:
city: Modena
country: Italy
facility: University of Modena and Reggio Emilia
Study officials:
affiliation: University of Modena and Reggio Emilia
name: Fabio Facchinetti, M.D.
role: STUDY_CHAIR
References:
citation: Facchinetti F, Vergani P, Di Tommaso M, Marozio L, Acaia B, Vicini R, Pignatti L, Locatelli A, Spitaleri M, Benedetto C, Zaina B, D'Amico R. Progestogens for Maintenance Tocolysis in Women With a Short Cervix: A Randomized Controlled Trial. Obstet Gynecol. 2017 Jul;130(1):64-70. doi: 10.1097/AOG.0000000000002065.