Vaginal Versus Intramuscular Progesterone for the Prevention of Recurrent Preterm Birth (VIP)
Primary Purpose
Premature Birth
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Vaginal Progesterone
Intramuscular Progesterone (17 alpha hydroxprogesterone caproate)
Sponsored by

About this trial
This is an interventional prevention trial for Premature Birth focused on measuring Progesterone, Prevention of preterm birth
Eligibility Criteria
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
Sites / Locations
- George Washington University
- Baystate Medical Center
- Thomas Jefferson University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Vaginal Progesterone
Intramuscular Progesterone
Arm Description
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
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.
Outcomes
Primary Outcome Measures
Preterm birth <37 weeks
Incidence of gestational age of delivery less than 37 weeks
Secondary Outcome Measures
Gestational age of delivery
Preterm birth <34 weeks and <28 weeks
Second trimester cervical length <25mm
Mode of delivery
Delivery mode- vaginal, cesarean, operative vaginal
Maternal mortality
5 minute Apgar score
Neonatal intensive care unit admission
Composite neonatal morbidity
(respiratory distress syndrome, grade III or IV intraventricular hemorrhage, culture proven sepsis, neonatal enterocolitis, and perinatal mortality up to 28 days of life)
Birthweight
Perinatal mortality up to 28 days of life
Medication side effects
Satisfaction with medication (5 point Likert scale)
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
Planned subgroup analysis for the outcome preterm birth <37 weeks, <34 weeks, <28 weeks
Planned subgroup analysis for the primary outcome as well as the secondary outcomes of preterm birth <34 weeks and <28 weeks 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.
Full Information
NCT ID
NCT02913495
First Posted
September 22, 2016
Last Updated
October 5, 2021
Sponsor
Thomas Jefferson University
Collaborators
Baystate Medical Center, George Washington University, Vriginia Commonwealth University, Ohio State University
1. Study Identification
Unique Protocol Identification Number
NCT02913495
Brief Title
Vaginal Versus Intramuscular Progesterone for the Prevention of Recurrent Preterm Birth
Acronym
VIP
Official Title
Vaginal Versus Intramuscular Progesterone for the Prevention of Recurrent Preterm Birth
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
September 2016 (Actual)
Primary Completion Date
August 2021 (Actual)
Study Completion Date
September 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Thomas Jefferson University
Collaborators
Baystate Medical Center, George Washington University, Vriginia Commonwealth University, Ohio State University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Premature Birth
Keywords
Progesterone, Prevention of preterm birth
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
205 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Vaginal Progesterone
Arm Type
Experimental
Arm Description
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
Arm Title
Intramuscular Progesterone
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Vaginal Progesterone
Other Intervention Name(s)
micronized progesterone
Intervention Type
Drug
Intervention Name(s)
Intramuscular Progesterone (17 alpha hydroxprogesterone caproate)
Other Intervention Name(s)
Makena
Primary Outcome Measure Information:
Title
Preterm birth <37 weeks
Description
Incidence of gestational age of delivery less than 37 weeks
Time Frame
up to 9 months (delivery)
Secondary Outcome Measure Information:
Title
Gestational age of delivery
Time Frame
up to 9 months (delivery)
Title
Preterm birth <34 weeks and <28 weeks
Time Frame
up to 9 months (delivery)
Title
Second trimester cervical length <25mm
Time Frame
2 months
Title
Mode of delivery
Description
Delivery mode- vaginal, cesarean, operative vaginal
Time Frame
up to 9 months (delivery)
Title
Maternal mortality
Time Frame
up to 9 months (delivery)
Title
5 minute Apgar score
Time Frame
up to 9 months (delivery)
Title
Neonatal intensive care unit admission
Time Frame
up to 9 months (delivery)
Title
Composite neonatal morbidity
Description
(respiratory distress syndrome, grade III or IV intraventricular hemorrhage, culture proven sepsis, neonatal enterocolitis, and perinatal mortality up to 28 days of life)
Time Frame
up to 9 months (delivery)
Title
Birthweight
Time Frame
up to 9 months (delivery)
Title
Perinatal mortality up to 28 days of life
Time Frame
up to 10 months (4 weeks after delivery)
Title
Medication side effects
Time Frame
up to 9 months (delivery)
Title
Satisfaction with medication (5 point Likert scale)
Time Frame
up to 9 months (delivery)
Title
Medication adherence
Description
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
Time Frame
up to 9 months (delivery)
Title
Planned subgroup analysis for the outcome preterm birth <37 weeks, <34 weeks, <28 weeks
Description
Planned subgroup analysis for the primary outcome as well as the secondary outcomes of preterm birth <34 weeks and <28 weeks 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.
Time Frame
up to 9 months (delivery)
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rupsa C Boelig, MD
Organizational Affiliation
Thomas Jefferson University Hospital; Sidney Kimmel Medical College
Official's Role
Principal Investigator
Facility Information:
Facility Name
George Washington University
City
Washington
State/Province
District of Columbia
Country
United States
Facility Name
Baystate Medical Center
City
Springfield
State/Province
Massachusetts
ZIP/Postal Code
01199
Country
United States
Facility Name
Thomas Jefferson University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing Plan Description
Results will be available, individual participant data may not be
Citations:
PubMed Identifier
22996126
Citation
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.
Results Reference
background
PubMed Identifier
27546354
Citation
Saccone 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.
Results Reference
background
PubMed Identifier
35189093
Citation
Boelig 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.
Results Reference
derived
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Vaginal Versus Intramuscular Progesterone for the Prevention of Recurrent Preterm Birth
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