Vaginal Versus Intramuscular Progesterone for the Prevention of Recurrent Preterm Birth (VIP)

February 9, 2026 updated by: Thomas Jefferson University
The purpose of this study is to evaluate the two suggested therapies for prevention of recurrent preterm birth (PTB) in women with a prior spontaneous preterm birth, vaginal and intramuscular progesterone to determine whether vaginal progesterone is superior to intramuscular progesterone in the prevention of recurrent preterm birth.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Preterm birth is one of the leading causes of neonatal morbidity and mortality. One of the greatest predictors of preterm birth is a history of prior spontaneous preterm birth. Presently 17 hydroxyprogesterone caproate (intramuscular) is the only FDA approved product for the prevention of recurrent preterm birth, however recent studies suggest that vaginal progesterone may be used for this purpose, and may even be superior. The American College of Obstetrics and Gynecology does not specify the optimal route of progesterone administration for the prevention of recurrent preterm birth. It is our intention to compare vaginal and intramuscular progesterone to see if one is superior.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
210

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • District of Columbia
      • Washington D.C., District of Columbia, United States
        • George Washington University
    • Massachusetts
      • Springfield, Massachusetts, United States, 01199
        • Baystate Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Pregnant women with singleton pregnancies
  • ≥18 years old
  • Estimated gestational age less than 24 0/7 weeks
  • Prior spontaneous preterm birth of a singleton pregnancy between 16 0/7-36 6/7 weeks.
  • Patients are also required provide consent, demonstrate an understanding of the purpose of the study, and agree to the study protocol.

Exclusion Criteria:

  • History of an adverse reaction to progesterone;
  • A contraindication to progesterone treatment;
  • Placenta previa or accreta;
  • Major fetal anomaly diagnosed on ultrasound or known chromosomal disorder;
  • Multifetal gestation;
  • Preterm labor, premature rupture of membranes, or clinical chorioamnionitis, at the time of enrollment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Vaginal Progesterone
200mg micronized progesterone vaginally, to be taken daily starting at 16 0/7 - 23 6/7 weeks, and continued daily until 36 6/7 weeks' gestation or delivery
Drug: Vaginal Progesterone
Other Names:
  • micronized progesterone
Active Comparator: Intramuscular Progesterone
250mg intramuscular progesterone to be administered weekly starting at 16 0/7 - 23 6/7 weeks, and continued weekly until 36 6/7 weeks' or delivery.
Drug: Intramuscular Progesterone (17 alpha hydroxprogesterone caproate)
Other Names:
  • Makena

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Preterm Birth <37 Weeks
Time Frame: up to 9 months (delivery)
Incidence of gestational age of delivery less than 37 weeks
up to 9 months (delivery)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Gestational Age of Delivery
Time Frame: up to 9 months (delivery)
Gestational age at delivery (weeks)
up to 9 months (delivery)
Preterm Birth <34 Weeks
Time Frame: up to 9 months (delivery)
Delivery of pregnancy 20 0/7 - 33 6/7 weeks gestation
up to 9 months (delivery)
Second Trimester Cervical Length <25mm
Time Frame: 2 months
Short cervix diagnosis (transvaginal ultrasound cervical length <=25mm prior to 24 weeks gestation
2 months
Mode of Delivery: Cesarean Section
Time Frame: up to 9 months (delivery)
Delivery mode- vaginal, cesarean, operative vaginal
up to 9 months (delivery)
Maternal Mortality
Time Frame: up to 9 months (delivery)
Maternal death for any reason from enrollment through hospital discharge from delivery hospitalization.
up to 9 months (delivery)
5 Minute Apgar Score<7
Time Frame: up to 9 months (delivery)
The Apgar score is based on a total score of 1 to 10. The higher the score, the better the baby is doing after birth. A score of 7, 8, or 9 is normal and is a sign that the newborn is in good health.
up to 9 months (delivery)
Neonatal Intensive Care Unit Admission
Time Frame: up to 9 months (delivery)
Admission to neonatal intensive care unit for any reason (yes/no)
up to 9 months (delivery)
Composite Neonatal Morbidity
Time Frame: up to 9 months (delivery)
Having at least one of the following: respiratory distress syndrome, grade III or IV intraventricular hemorrhage, culture proven sepsis, neonatal enterocolitis, or perinatal mortality up to 28 days of life
up to 9 months (delivery)
Birthweight
Time Frame: up to 9 months (delivery)
Birthweight assessed at delivery (grams)
up to 9 months (delivery)
Perinatal Mortality up to 28 Days of Life
Time Frame: up to 10 months (4 weeks after delivery)
In utero or neonatal death from enrollment through 28 days of neonatal life.
up to 10 months (4 weeks after delivery)
Medication Side Effects
Time Frame: up to 9 months (delivery)
Medication side effects
up to 9 months (delivery)
Satisfaction With Medication (5 Point Likert Scale)
Time Frame: up to 9 months (delivery)
5 point scale, 0 is very dissatisfied, 5 is very satisfied, 3 is neutral
up to 9 months (delivery)
Medication Adherence
Time Frame: up to 9 months (delivery)

Vaginal progesterone:

  • Overall adherence: #days used/#days of treatment x 100
  • Non-adherent: ≥4 days between doses

Intramuscular progesterone:

  • Overall adherence: #weeks used/#weeks of treatment x 100
  • Non-adherent: ≥10 days between doses
up to 9 months (delivery)
Planned Subgroup Analysis for the Outcome Preterm Birth <37 Weeks, <34 Weeks, <28 Weeks
Time Frame: up to 9 months (delivery)
Planned subgroup analysis for the primary outcome of patients with a cervical length <25mm versus ≥25mm, history-indicated cerclage versus not, and for those started on progesterone 16-20 weeks versus 20-24 weeks.
up to 9 months (delivery)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Thomas Jefferson University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Ohio State University
George Washington University
Baystate Medical Center
Vriginia Commonwealth University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Rupsa C Boelig, MD, Thomas Jefferson University Hospital; Sidney Kimmel Medical College

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 22, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 22, 2016

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 23, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 24, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 9, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 16D.542

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Results will be available, individual participant data may not be

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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