Progestagens for the Tertiary Prophylaxis of Preterm Delivery

Study Overview
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Brief Summary
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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
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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.

Official Title
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Progestagens for the Tertiary Prophylaxis of Preterm Delivery in Women With Short Cervix. A Randomized Multicentre Trial

Conditions
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Preterm Delivery, Neonatal Complications

Intervention / Treatment
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* Drug: 17 alpha-hydroxy progesterone caproate
* Drug: micronized Progesterone
* Procedure: Control


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 17 alfa hydroxy Progesterone caproate<br>Women treated with i.m. 17P injection/weekly (Lentogest, IBSA, Italy) | Drug: 17 alpha-hydroxy progesterone caproate<br>* weekly injection of 17 P<br>* Other names: Lentogest;|
| Active Comparator: Micronized Progesterone<br>micronized P 200 mg per vagina /day (Utrogestan, Besins Healthcare, Belgium) | Drug: micronized Progesterone<br>* daily administration of vaginal progesterone<br>* Other names: Utrogestan;|
| Active Comparator: Control<br>Routine clinical controls | Procedure: Control<br> <br> * Other names: Routine clinical cares;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Preterm delivery (37 weeks of gestation) |  | 6 mo. after end of recruitment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delivery <32, <35 wks |  | 6 months after the end of the study | 
| Hospital admissions before delivery |  | 6 months after the end of the study | 
| Gestational age at delivery |  | 6 months after the end of the study | 
| Birth-weight centile |  | 6 months after the end of the study | 
| NICU admission |  | 6 months after the end of the study | 
| days of NICU admission |  | 6 months after the end of the study | 
| days of oxygen supply |  | 6 months after the end of the study | 
| composite neonatal complications | Include: RDS, IVH, ROP, PVL, NEC, Sepsis | 6 months after the end of the study | 
| congenital neonatal anomalies |  | 6 months after the end of the study | 
| congenital neonatal malformations |  | 6 months after the end of the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Progestagens, Tertiary Prophylaxis, Micronized Progesterone, 17 alpha hydroxy P, Preterm Delivery, Cervical shortening