Progestagens for the Tertiary Prophylaxis of Preterm Delivery

Preterm Delivery Clinical Trial

— PROTECT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01178788
• Other study ID #: 2009-017441-63
• Status: Completed
• Phase: Phase 3
• First received: July 8, 2010
• Last updated: September 21, 2016
• Start date: February 2010
• Est. completion date: December 2015

Study information

• Verified date: September 2016
• Source: University of Modena and Reggio Emilia
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 254
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Neonatal Complications
• Premature Birth
• Preterm Delivery

Intervention

Drug:
• 17 alpha-hydroxy progesterone caproate
weekly injection of 17 P
• micronized Progesterone
daily administration of vaginal progesterone

Procedure:
• Control

Locations

Country	Name	City	State
Italy	University of Modena and Reggio Emilia	Modena

Sponsors (1)

Lead Sponsor	Collaborator
University of Modena and Reggio Emilia

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Preterm delivery (37 weeks of gestation)		6 mo. after end of recruitment	No
Secondary	Delivery <32, <35 wks		6 months after the end of the study	No
Secondary	Hospital admissions before delivery		6 months after the end of the study	Yes
Secondary	Gestational age at delivery		6 months after the end of the study	No
Secondary	Birth-weight centile		6 months after the end of the study	No
Secondary	NICU admission		6 months after the end of the study	No
Secondary	days of NICU admission		6 months after the end of the study	No
Secondary	days of oxygen supply		6 months after the end of the study	No
Secondary	composite neonatal complications	Include: RDS, IVH, ROP, PVL, NEC, Sepsis	6 months after the end of the study	No
Secondary	congenital neonatal anomalies		6 months after the end of the study	No
Secondary	congenital neonatal malformations		6 months after the end of the study	No