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Progestagens for the Tertiary Prophylaxis of Preterm Delivery (PROTECT)

U

University of Modena and Reggio Emilia

Status and phase

Completed
Phase 3

Conditions

Preterm Delivery
Neonatal Complications

Treatments

Drug: micronized Progesterone
Procedure: Control
Drug: 17 alpha-hydroxy progesterone caproate

Study type

Interventional

Funder types

Other

Identifiers

NCT01178788
2009-017441-63

Details and patient eligibility

About

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.

Full 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.

Enrollment

254 patients

Sex

Female

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Prevention

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

254 participants in 3 patient groups

17 alfa hydroxy Progesterone caproate
Active Comparator group
Description:
Women treated with i.m. 17P injection/weekly (Lentogest, IBSA, Italy)
Treatment:
Drug: 17 alpha-hydroxy progesterone caproate
Micronized Progesterone
Active Comparator group
Description:
micronized P 200 mg per vagina /day (Utrogestan, Besins Healthcare, Belgium)
Treatment:
Drug: micronized Progesterone
Control
Active Comparator group
Description:
Routine clinical controls
Treatment:
Procedure: Control

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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