Premature BirthPhase 4VIPNCT02913495
Vaginal Versus Intramuscular Progesterone for the Prevention of Recurrent Preterm Birth
A Phase 4 study testing Vaginal Progesterone and Intramuscular Progesterone (17 alpha hydroxprogesterone caproate) in people with Premature Birth, run by Thomas Jefferson University at 3 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Premature Birth
- What is being tested?
- Vaginal Progesterone and Intramuscular Progesterone (17 alpha hydroxprogesterone caproate)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 210 participants
- Where
- 3 sitesUnited States
- Study dates
- Sep 2016to Sep 2021
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
Baystate Medical Center
Springfield, Massachusetts, 01199
George Washington University
Washington D.C., District of Columbia
About this study
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.
Read the 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.
- Conditions
- Premature Birth
- Being tested
- Vaginal Progesterone, Intramuscular Progesterone (17 alpha hydroxprogesterone caproate)
- Keywords
- Progesterone, Prevention of preterm birth
- Medical subject headings
- Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vaginal ProgesteroneDrug
Also called micronized progesterone
Intramuscular Progesterone (17 alpha hydroxprogesterone caproate)Drug
Also called Makena
| Study group | Role | What they receive |
|---|---|---|
| Vaginal Progesterone | Experimental | 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 Receives: Drug: Vaginal Progesterone |
| Intramuscular Progesterone | Active comparator | 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. Receives: Drug: Intramuscular Progesterone (17 alpha hydroxprogesterone caproate) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Preterm Birth <37 Weeks
Incidence of gestational age of delivery less than 37 weeks
Measured: up to 9 months (delivery)
Secondary outcomes (14)
Gestational Age of Delivery
Gestational age at delivery (weeks)
Measured: up to 9 months (delivery)
Preterm Birth <34 Weeks
Delivery of pregnancy 20 0/7 - 33 6/7 weeks gestation
Measured: up to 9 months (delivery)
Second Trimester Cervical Length <25mm
Short cervix diagnosis (transvaginal ultrasound cervical length <=25mm prior to 24 weeks gestation
Measured: 2 months
Mode of Delivery: Cesarean Section
Delivery mode- vaginal, cesarean, operative vaginal
Measured: up to 9 months (delivery)
Maternal Mortality
Maternal death for any reason from enrollment through hospital discharge from delivery hospitalization.
Measured: up to 9 months (delivery)
5 Minute Apgar Score<7
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.
Measured: up to 9 months (delivery)
Neonatal Intensive Care Unit Admission
Admission to neonatal intensive care unit for any reason (yes/no)
Measured: up to 9 months (delivery)
Composite Neonatal Morbidity
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
Measured: up to 9 months (delivery)
Birthweight
Birthweight assessed at delivery (grams)
Measured: up to 9 months (delivery)
Perinatal Mortality up to 28 Days of Life
In utero or neonatal death from enrollment through 28 days of neonatal life.
Measured: up to 10 months (4 weeks after delivery)
Medication Side Effects
Medication side effects
Measured: up to 9 months (delivery)
Satisfaction With Medication (5 Point Likert Scale)
5 point scale, 0 is very dissatisfied, 5 is very satisfied, 3 is neutral
Measured: up to 9 months (delivery)
Medication Adherence
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
Measured: up to 9 months (delivery)
Planned Subgroup Analysis for the Outcome Preterm Birth <37 Weeks, <34 Weeks, <28 Weeks
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.
Measured: up to 9 months (delivery)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2016 (estimated)
- Study startSep 2016
- Primary completionAug 2021
- Study completionSep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Premature BirthStudies of the same condition, open and under way.
- More trials run by Thomas Jefferson UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 210 participants (actual)
Sponsor and investigators
- Lead sponsor
- Thomas Jefferson University
- Sponsor type
- University, hospital or other
- Collaborators
- Baystate Medical Center, George Washington University, Vriginia Commonwealth University, Ohio State University
- Responsible party
- Sponsor
- Investigators
- Rupsa C Boelig, MD, Principal investigator, Thomas Jefferson University Hospital; Sidney Kimmel Medical College
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02913495
- Sponsor's protocol ID
- 16D.542
- Acronym
- VIP
- Status last verified
- Feb 2026
- First submitted
- 22 Sep 2016
- Last updated
- 24 Feb 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided: Results will be available, individual participant data may not be
Publications
Committee on Practice Bulletins-Obstetrics, The American College of Obstetricians and Gynecologists. Practice bulletin no. 130: prediction and prevention of preterm birth. Obstet Gynecol. 2012 Oct;120(4):964-73. doi: 10.1097/AOG.0b013e3182723b1b. No abstract available.
PubMed 22996126Saccone G, Khalifeh A, Elimian A, Bahrami E, Chaman-Ara K, Bahrami MA, Berghella V. Vaginal progesterone vs intramuscular 17alpha-hydroxyprogesterone caproate for prevention of recurrent spontaneous preterm birth in singleton gestations: systematic review and meta-analysis of randomized controlled trials. Ultrasound Obstet Gynecol. 2017 Mar;49(3):315-321. doi: 10.1002/uog.17245. Epub 2017 Feb 6.
PubMed 27546354Boelig RC, Schoen CN, Frey H, Gimovsky AC, Springel E, Backley S, Berghella V. Vaginal progesterone vs intramuscular 17-hydroxyprogesterone caproate for prevention of recurrent preterm birth: a randomized controlled trial. Am J Obstet Gynecol. 2022 May;226(5):722.e1-722.e12. doi: 10.1016/j.ajog.2022.02.012. Epub 2022 Feb 19.
PubMed 35189093
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vaginal Versus Intramuscular Progesterone for the Prevention of Recurrent Preterm Birth
- ClinicalTrials.gov ID
- NCT02913495
- Acronym / sponsor ID
- VIP / 16D.542
- Conditions
- Premature Birth
- Keywords
- Progesterone, Prevention of preterm birth
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 210 participants (actual)
- Lead sponsor
- Thomas Jefferson UniversityUniversity, hospital or other
- Collaborators
- Baystate Medical Center, George Washington University, Vriginia Commonwealth University, Ohio State University
- Study start
- Sep 2016 (actual)
- Primary completion
- Aug 2021 (actual)
- Study completion
- Sep 2021 (actual)
- First posted
- 23 Sep 2016 (estimated)
- Results
- Posted 24 Feb 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vaginal Progesterone | Experimental | Drug: Vaginal Progesterone200mg 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 |
| Intramuscular Progesterone | Active comparator | Drug: Intramuscular Progesterone (17 alpha hydroxprogesterone caproate)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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (6 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vaginal ProgesteroneAlso: micronized progesterone | Drug | Vaginal Progesterone |
| Intramuscular Progesterone (17 alpha hydroxprogesterone caproate)Also: Makena | Drug | Intramuscular Progesterone |
Primary outcome
Preterm Birth <37 Weeks
Time frame: up to 9 months (delivery)
Incidence of gestational age of delivery less than 37 weeks
14 secondary outcomes
Gestational Age of Delivery
Time frame: up to 9 months (delivery)
Preterm Birth <34 Weeks
Time frame: up to 9 months (delivery)
Second Trimester Cervical Length <25mm
Time frame: 2 months
Mode of Delivery: Cesarean Section
Time frame: up to 9 months (delivery)
Maternal Mortality
Time frame: up to 9 months (delivery)
5 Minute Apgar Score<7
Time frame: up to 9 months (delivery)
Neonatal Intensive Care Unit Admission
Time frame: up to 9 months (delivery)
Composite Neonatal Morbidity
Time frame: up to 9 months (delivery)
Birthweight
Time frame: up to 9 months (delivery)
Perinatal Mortality up to 28 Days of Life
Time frame: up to 10 months (4 weeks after delivery)
Medication Side Effects
Time frame: up to 9 months (delivery)
Satisfaction With Medication (5 Point Likert Scale)
Time frame: up to 9 months (delivery)
Medication Adherence
Time frame: 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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22996126Committee on Practice Bulletins-Obstetrics, The American College of Obstetricians and Gynecologists. Practice bulletin no. 130: prediction and prevention of preterm birth. Obstet Gynecol. 2012 Oct;120(4):964-73. doi: 10.1097/AOG.0b013e3182723b1b. No abstract available.
- Background: PubMed 27546354Saccone G, Khalifeh A, Elimian A, Bahrami E, Chaman-Ara K, Bahrami MA, Berghella V. Vaginal progesterone vs intramuscular 17alpha-hydroxyprogesterone caproate for prevention of recurrent spontaneous preterm birth in singleton gestations: systematic review and meta-analysis of randomized controlled trials. Ultrasound Obstet Gynecol. 2017 Mar;49(3):315-321. doi: 10.1002/uog.17245. Epub 2017 Feb 6.
- Derived from this study: PubMed 35189093Boelig RC, Schoen CN, Frey H, Gimovsky AC, Springel E, Backley S, Berghella V. Vaginal progesterone vs intramuscular 17-hydroxyprogesterone caproate for prevention of recurrent preterm birth: a randomized controlled trial. Am J Obstet Gynecol. 2022 May;226(5):722.e1-722.e12. doi: 10.1016/j.ajog.2022.02.012. Epub 2022 Feb 19.
- Individual participant dataSharing planned: Undecided. Results will be available, individual participant data may not be
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rupsa C Boelig, MD principal investigator
Thomas Jefferson University Hospital; Sidney Kimmel Medical College
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Vaginal Progesterone and Intramuscular Progesterone (17 alpha hydroxprogesterone caproate) in people with Premature Birth, run by Thomas Jefferson University at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Feb 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Preterm Birth <37 Weeks (time frame: up to 9 months (delivery)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02913495, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2026.