Comparison Between Natural Progesterone and Vaginal Pessary for the Prevention of Spontaneous Preterm Birth (PAP-C)

Comparison Between Natural Progesterone and Vaginal Pessary for the Prevention of Spontaneous Preterm Birth in Pregnant Women With a Uterine Cervix Measuring 25 mm or Less in Length

The aim of this study is to compare the effectiveness between the cervical pessary and the natural progesterone in reduction of preterm birth rates in pregnant women with a uterine cervical length of 25 mm or less evaluated by transvaginal ultrasonography.

Study Overview

• Status: Completed
• Conditions: Premature Birth; Preterm Labor
• Intervention / Treatment: Device: cervical pessary; Drug: natural progesterone

Detailed Description

Preterm birth is the leading cause of perinatal morbidity and mortality. The rates of spontaneous premature labor have not changed much during the past 10 years. A significant decrease in mortality and morbidity of premature babies will only be possible if women at risk of spontaneous preterm birth are accurately identified and administered preventive therapies. Ultrasonographic measurement of the cervix between 20 and 24 weeks of gestation can improve the identification of both women with single pregnancies and those with twin pregnancies at risk. Asymptomatic women with a short uterine cervix (25 mm or less) are at increased risk of spontaneous premature labor.

The prophylactic use of progesterone during the early phase of pregnancy in women with a history of preterm birth and those with a short cervix can prevent preterm birth.

The cervical pessary is a device used also for the prevention of preterm birth. Vaginal infections are also important causes of preterm birth. There are not many studies about the vaginal microbiome in pregnant women.

Measurement of cervical length is used as a screening test because it is inexpensive, has a short learning curve, and is well tolerated by patients. In addition, placement and removal of the pessary is an easy, accessible, and noninvasive procedure. The results on the concentration of omega 3 and preterm birth are still conflicting.

The aim of this study is to compare the effectiveness of the cervical pessary and the natural progesterone in reduction of preterm birth rates in pregnant women with a uterine cervix measuring 25 mm or less in length as evaluated by transvaginal ultrasonography, assess whether there is a relationship between maternal plasma concentration of omega 3 and preterm birth, and compare the microbiome in these women.

Methods: A prospective randomized controlled trial including pregnant women at the time of morphological ultrasound between 20 and 23 weeks and 6 days of pregnancy. Pregnant women in this gestational age with cervical length of 25 mm or less will be randomized between the conduct and the inclusion of progesterone vaginal pessary. In patients of both groups vaginal discharge sample will be collected at the time of randomization.

• Study Type: Interventional
• Enrollment (Actual): 203
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • São Paulo
    • São Paulo, São Paulo, Brazil, 05403-000
      • Hospital Das Clinicas Da Faculdade De Medicina Da USP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• gestational age between 20 weeks and 23 weeks and 6 days
• singleton pregnancies

Exclusion Criteria:

• fetal death at randomization
• major structural or chromosomal abnormality
• cervical cerclage in the current pregnancy
• preterm rupture of membranes diagnosed before randomization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: cervical pessary; Patients with uterine cervical length ≤ 25 mm are randomized to use the cervical pessary or natural progesterone to compare their effectiveness in the reduction of preterm birth rates.	Device: cervical pessary
Active Comparator: natural progesterone; Patients with uterine cervical length ≤ 25 mm are randomized to use the cervical pessary or natural progesterone to compare their effectiveness in the reduction of preterm birth rates.	Drug: natural progesterone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spontaneous preterm birth before 34 weeks of gestational age	All births that occurred before 34 weeks of gestation were included, excluding iatrogenic births (medically indicated).	before 34 weeks of gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall preterm birth before 37, 34, 32 and 30 weeks of gestational age	All births (spontaneous and iatrogenic) that occurred before 37, 34, 32 and 30 weeks of gestation were included.	before 37, 34, 32 and 30 weeks of gestation
Spontaneous preterm birth before 37, 32 and 30 weeks of gestational age	All births that occurred before 37, 32 and 30 weeks of gestation were	before 37, 32 and 30 weeks of gestation
Adverse neonatal events	Intraventricular hemorrhage, respiratory distress syndrome, retinopathy of prematurity and necrotizing enterocolitis	Neonatal period (up to 27 days after birth)
The need of neonatal special care	admission to neonatal intensive care unit [NICU], mechanical ventilation, phototherapy, treatment for sepsis and blood transfusion	Neonatal period (up to 27 days after birth)

Collaborators and Investigators

• Sponsor: University of Sao Paulo

Study record dates

Study Major Dates

• Study Start (Actual): August 3, 2015
• Primary Completion (Actual): December 10, 2022
• Study Completion (Actual): August 30, 2023

Study Registration Dates

• First Submitted: July 6, 2015
• First Submitted That Met QC Criteria: July 27, 2015
• First Posted (Estimated): July 30, 2015

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 17, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: progesterone; cervical pessary; uterine cervix
• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor Complications; Pregnancy Complications; Premature Birth; Obstetric Labor, Premature; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Progesterone
• Other Study ID Numbers: 470.095