Progestagens for the Tertiary Prophylaxis of Preterm Delivery (PROTECT)
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.
|Preterm Delivery Neonatal Complications||Drug: 17 alpha-hydroxy progesterone caproate Drug: micronized Progesterone Procedure: Control||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||Progestagens for the Tertiary Prophylaxis of Preterm Delivery in Women With Short Cervix. A Randomized Multicentre Trial|
- Preterm delivery (37 weeks of gestation) [ Time Frame: 6 mo. after end of recruitment ]
- Delivery <32, <35 wks [ Time Frame: 6 months after the end of the study ]
- Hospital admissions before delivery [ Time Frame: 6 months after the end of the study ]
- Gestational age at delivery [ Time Frame: 6 months after the end of the study ]
- Birth-weight centile [ Time Frame: 6 months after the end of the study ]
- NICU admission [ Time Frame: 6 months after the end of the study ]
- days of NICU admission [ Time Frame: 6 months after the end of the study ]
- days of oxygen supply [ Time Frame: 6 months after the end of the study ]
- composite neonatal complications [ Time Frame: 6 months after the end of the study ]Include: RDS, IVH, ROP, PVL, NEC, Sepsis
- congenital neonatal anomalies [ Time Frame: 6 months after the end of the study ]
- congenital neonatal malformations [ Time Frame: 6 months after the end of the study ]
|Study Start Date:||February 2010|
|Study Completion Date:||December 2015|
|Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Active Comparator: 17 alfa hydroxy Progesterone caproate
Women treated with i.m. 17P injection/weekly (Lentogest, IBSA, Italy)
Drug: 17 alpha-hydroxy progesterone caproate
weekly injection of 17 P
Other Name: Lentogest
Active Comparator: Micronized Progesterone
micronized P 200 mg per vagina /day (Utrogestan, Besins Healthcare, Belgium)
Drug: micronized Progesterone
daily administration of vaginal progesterone
Other Name: Utrogestan
Active Comparator: Control
Routine clinical controls
Other Name: Routine clinical cares
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01178788
|University of Modena and Reggio Emilia|
|Modena, Italy, 41100|
|Study Chair:||Fabio Facchinetti, M.D.||University of Modena and Reggio Emilia|