Premature BirthPALNCT01840228
Vaginal Progesterone for the Prevention of Preterm Birth in Women With Arrested Preterm Labor
A study testing Micronized progesterone suppository in people with Premature Birth and Obstetric Labor, Premature, run by Washington University School of Medicine at 1 site in United States.
Trial summary
Preterm birth, defined as birth before 37 weeks' gestation, is a leading cause of infant death and disease. Progesterone is the single most effective intervention in the prevention of preterm birth. Read more about this study
- Who is it for?
- Ages 18 to 50 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Premature Birth, Obstetric Labor, Premature
- What is being tested?
- Micronized progesterone suppository
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- May 2013to 7 May 2018
- Phase
- Interventional
- 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 to 50 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Singleton or twin gestation
- Estimated gestational age between 24 0/7 and 33 6/7 weeks' gestation
- Initially present with regular contractions and clinical diagnosis of preterm labor but remain undelivered with 1) no further cervical change 12 hours after discontinuation of acute tocolytic therapy; or 2) be considered eligible for discharge based on attending physician judgment prior to the 12 hour period of time
- The participant's cervix must be at least 1 cm at the time of enrollment
Who cannot join
- Non-English speaking
- Rupture of membranes
- Chorioamnionitis
- Non-reassuring fetal status
- Maternal indication for delivery
- Placental abruption
Show all 11Show fewer
- Intrauterine fetal demise
- Prenatally diagnosed major fetal anomaly
- Cervical cerclage in place
- Previous administration of progesterone during the current pregnancy for a history of preterm birth or short cervix
- Participant is either unwilling or unable to attend follow-up study visits following hospital discharge
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine/ Barnes-Jewish Hospital
St Louis, Missouri, 63110
About this study
Preterm birth, defined as birth before 37 weeks' gestation, is a leading cause of infant death and disease. Progesterone is the single most effective intervention in the prevention of preterm birth. However, current use of this therapy is limited to certain high-risk groups including women with a history of preterm birth and women with a short cervix. This study seeks to evaluate the efficacy of this preventive therapy in another high-risk group: women with arrested preterm labor. The investigators hypothesize that administration of vaginal progesterone in women who present with preterm labor but remain undelivered 12 hours after cessation of short-term therapy to inhibit contractions will result in lower rates of preterm birth before 37 weeks' than will administration of placebo.
Read the detailed description
RESEARCH DESIGN AND METHODS
The investigators will perform a randomized, blinded, placebo-controlled trial to evaluate the use of vaginal progesterone in women with arrested preterm labor after 24 weeks' gestation to reduce the risk of preterm birth before 37 weeks' gestation. Women enrolled in the study will be randomized to daily vaginal administration of progesterone (200 mg) or placebo from time of enrollment until 36 6/7 weeks' gestation. Women will be eligible if they have a singleton or twin gestation between 24 0/7 and 33 6/7 weeks' gestation and initially present with regular uterine contractions and a clinical diagnosis of preterm labor but remain undelivered without further cervical change 12 hours after discontinuation of acute tocolytic therapy. Women may also participate if it has been less than if they are considered eligible for discharge based on attending physician judgement prior to the 12 hour period of time.
Randomization and Blinding- Participants in the study will be randomized using a computer-generated randomization scheme with 1:1 allocation to receive progesterone or placebo. Investigators and research team members, participants, and the obstetric providers will be blinded to the allocated intervention.
Procedures-
- Data collection- Information will be recorded from the participant's medical record. Additional study information not included in the medical record will be obtained directly from the participant in an interview with the research team member.
- Follow-up- Regardless of whether the participant remains hospitalized or is discharged prior to delivery, she will meet with a study coordinator every 2 weeks. During the follow-up visit, a study team member will discuss compliance with the study drug and possible side effects. The participant will fill out a 1-page questionnaire that asks questions about compliance and side effects. This information will be recorded and provided to the Data Safety and Monitoring Board at the midpoint review.
SAMPLE SIZE ESTIMATION
The investigators plan to enroll 120 patients, with a 1:1 allocation to treatment and placebo. This sample size is adequate to detect a one-half reduction in the primary outcome, delivery before 37 weeks.
STATISTICAL ANALYSIS
Baseline characteristics of women randomized to progesterone will be compared with women randomized to placebo. Rates of delivery before 37 weeks' gestation will be compared among the groups using the Chi-square test. Secondary outcomes will be evaluated using the Chi-square test for binary outcomes and the Student t-test for continuous outcomes. Length of time from enrollment to delivery will be analyzed using Kaplan-Meier curves and the Cox proportional hazards model. All analyses will be performed using the intention-to-treat principle.
- Conditions
- Premature Birth, Obstetric Labor, Premature
- Being tested
- Micronized progesterone suppository
- Keywords
- Preterm, Progesterone
- Medical subject headings
- Premature Birth, Obstetric Labor, Premature
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Micronized progesterone suppositoryDrug
| Study group | Role | What they receive |
|---|---|---|
| Micronized progesterone suppository | Active comparator | Micronized progesterone suppository 200 mg vaginally daily until 36 6/7 weeks' gestation. Receives: Drug: Micronized progesterone suppository |
| Placebo suppository | Placebo comparator | One placebo suppository vaginally daily until 36 6/7 weeks' gestation. Receives: Drug: Micronized progesterone suppository |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Delivered Before 37 Weeks'
Measured: Duration of current pregnancy, anticipated maximum 18 weeks
Secondary outcomes (7)
Number of Participants Who Delivered Before 34 Weeks'
Evaluated in women enrolled prior to 32 weeks gestation
Measured: Duration of current pregnancy, anticipated maximum 18 weeks
Delivery Within 2 Weeks of Randomization
Measured: 2 weeks
Number of Weeks Pregnancy Prolongation
Measured: Duration of current pregnancy, anticipated maximum 18 weeks
Infant Birth Weight
Measured: Day of delivery in current pregnancy
Neonatal Intensive Care Unit Admission
Measured: Followed for duration of neonatal hospital stay, estimated maximum 16 weeks
Number of Participants With Chorioamnionitis
Measured: Duration of current pregnancy, anticipated maximum 18 weeks
Composite Neonatal Outcome
A composite neonatal outcome comprising neonatal death, respiratory distress syndrome, bronchopulmonary dysplasia, severe (grade III/IV) interventricular hemorrhage, necrotizing enterocolitis, and sepsis.
Measured: Followed for duration of neonatal hospital stay, estimated maximum 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2013 (estimated)
- Study startMay 2013
- Primary completion7 May 2018
- Study completion7 May 2018
Why it stopped: Low enrollment rate
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 (6)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 Washington University School of MedicineThe 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Thrasher Research Fund
- Responsible party
- Sponsor
- Investigators
- George A Macones, MD, MSCE, Study chair, Washington University School of MedicineHeather A Frey, MD, MSCI, Principal investigator, Ohio State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01840228
- Sponsor's protocol ID
- 201301148
- Acronym
- PAL
- Status last verified
- May 2019
- First submitted
- 17 Apr 2013
- Last updated
- 18 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Lyell DJ, Pullen KM, Mannan J, Chitkara U, Druzin ML, Caughey AB, El-Sayed YY. Maintenance nifedipine tocolysis compared with placebo: a randomized controlled trial. Obstet Gynecol. 2008 Dec;112(6):1221-1226. doi: 10.1097/AOG.0b013e31818d8386.
PubMed 19037029Likis FE, Edwards DR, Andrews JC, Woodworth AL, Jerome RN, Fonnesbeck CJ, McKoy JN, Hartmann KE. Progestogens for preterm birth prevention: a systematic review and meta-analysis. Obstet Gynecol. 2012 Oct;120(4):897-907. doi: 10.1097/AOG.0b013e3182699a15.
PubMed 22955308Hassan SS, Romero R, Vidyadhari D, Fusey S, Baxter JK, Khandelwal M, Vijayaraghavan J, Trivedi Y, Soma-Pillay P, Sambarey P, Dayal A, Potapov V, O'Brien J, Astakhov V, Yuzko O, Kinzler W, Dattel B, Sehdev H, Mazheika L, Manchulenko D, Gervasi MT, Sullivan L, Conde-Agudelo A, Phillips JA, Creasy GW; PREGNANT Trial. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2011 Jul;38(1):18-31. doi: 10.1002/uog.9017. Epub 2011 Jun 15.
PubMed 21472815Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH; Fetal Medicine Foundation Second Trimester Screening Group. Progesterone and the risk of preterm birth among women with a short cervix. N Engl J Med. 2007 Aug 2;357(5):462-9. doi: 10.1056/NEJMoa067815.
PubMed 17671254Borna S, Sahabi N. Progesterone for maintenance tocolytic therapy after threatened preterm labour: a randomised controlled trial. Aust N Z J Obstet Gynaecol. 2008 Feb;48(1):58-63. doi: 10.1111/j.1479-828X.2007.00803.x.
PubMed 18275573Arikan I, Barut A, Harma M, Harma IM. Effect of progesterone as a tocolytic and in maintenance therapy during preterm labor. Gynecol Obstet Invest. 2011;72(4):269-73. doi: 10.1159/000328719. Epub 2011 Nov 12.
PubMed 22086108
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vaginal Progesterone for the Prevention of Preterm Birth in Women With Arrested Preterm Labor
- ClinicalTrials.gov ID
- NCT01840228
- Acronym / sponsor ID
- PAL / 201301148
- Conditions
- Premature Birth, Obstetric Labor, Premature
- Keywords
- Preterm, Progesterone
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low enrollment rate
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- Thrasher Research Fund
- Study start
- May 2013
- Primary completion
- 7 May 2018 (actual)
- Study completion
- 7 May 2018 (actual)
- First posted
- 25 Apr 2013 (estimated)
- Results
- Posted 18 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Preterm birth, defined as birth before 37 weeks' gestation, is a leading cause of infant death and disease. Progesterone is the single most effective intervention in the prevention of preterm birth. However, current use of this therapy is limited to certain high-risk groups including women with a history of preterm birth and women with a short cervix. This study seeks to evaluate the efficacy of this preventive therapy in another high-risk group: women with arrested preterm labor. The investigators hypothesize that administration of vaginal progesterone in women who present with preterm labor but remain undelivered 12 hours after cessation of short-term therapy to inhibit contractions will result in lower rates of preterm birth before 37 weeks' than will administration of placebo.
Detailed description
RESEARCH DESIGN AND METHODS
The investigators will perform a randomized, blinded, placebo-controlled trial to evaluate the use of vaginal progesterone in women with arrested preterm labor after 24 weeks' gestation to reduce the risk of preterm birth before 37 weeks' gestation. Women enrolled in the study will be randomized to daily vaginal administration of progesterone (200 mg) or placebo from time of enrollment until 36 6/7 weeks' gestation. Women will be eligible if they have a singleton or twin gestation between 24 0/7 and 33 6/7 weeks' gestation and initially present with regular uterine contractions and a clinical diagnosis of preterm labor but remain undelivered without further cervical change 12 hours after discontinuation of acute tocolytic therapy. Women may also participate if it has been less than if they are considered eligible for discharge based on attending physician judgement prior to the 12 hour period of time.
Randomization and Blinding- Participants in the study will be randomized using a computer-generated randomization scheme with 1:1 allocation to receive progesterone or placebo. Investigators and research team members, participants, and the obstetric providers will be blinded to the allocated intervention.
Procedures-
- Data collection- Information will be recorded from the participant's medical record. Additional study information not included in the medical record will be obtained directly from the participant in an interview with the research team member.
- Follow-up- Regardless of whether the participant remains hospitalized or is discharged prior to delivery, she will meet with a study coordinator every 2 weeks. During the follow-up visit, a study team member will discuss compliance with the study drug and possible side effects. The participant will fill out a 1-page questionnaire that asks questions about compliance and side effects. This information will be recorded and provided to the Data Safety and Monitoring Board at the midpoint review.
SAMPLE SIZE ESTIMATION
The investigators plan to enroll 120 patients, with a 1:1 allocation to treatment and placebo. This sample size is adequate to detect a one-half reduction in the primary outcome, delivery before 37 weeks.
STATISTICAL ANALYSIS
Baseline characteristics of women randomized to progesterone will be compared with women randomized to placebo. Rates of delivery before 37 weeks' gestation will be compared among the groups using the Chi-square test. Secondary outcomes will be evaluated using the Chi-square test for binary outcomes and the Student t-test for continuous outcomes. Length of time from enrollment to delivery will be analyzed using Kaplan-Meier curves and the Cox proportional hazards model. All analyses will be performed using the intention-to-treat principle.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Micronized progesterone suppository | Active comparator | Drug: Micronized progesterone suppositoryMicronized progesterone suppository 200 mg vaginally daily until 36 6/7 weeks' gestation. |
| Placebo suppository | Placebo comparator | Drug: Micronized progesterone suppositoryOne placebo suppository vaginally daily until 36 6/7 weeks' gestation. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Singleton or twin gestation
- Estimated gestational age between 24 0/7 and 33 6/7 weeks' gestation
- Initially present with regular contractions and clinical diagnosis of preterm labor but remain undelivered with 1) no further cervical change 12 hours after discontinuation of acute tocolytic therapy; or 2) be considered eligible for discharge based on attending physician judgment prior to the 12 hour period of time
- The participant's cervix must be at least 1 cm at the time of enrollment
Key exclusion criteria (11 listed)
- Non-English speaking
- Rupture of membranes
- Chorioamnionitis
- Non-reassuring fetal status
- Maternal indication for delivery
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 |
|---|---|---|
| Micronized progesterone suppository | Drug | Micronized progesterone suppository, Placebo suppository |
Primary outcome
Number of Participants Who Delivered Before 37 Weeks'
Time frame: Duration of current pregnancy, anticipated maximum 18 weeks
7 secondary outcomes
Number of Participants Who Delivered Before 34 Weeks'
Time frame: Duration of current pregnancy, anticipated maximum 18 weeks
Delivery Within 2 Weeks of Randomization
Time frame: 2 weeks
Number of Weeks Pregnancy Prolongation
Time frame: Duration of current pregnancy, anticipated maximum 18 weeks
Infant Birth Weight
Time frame: Day of delivery in current pregnancy
Neonatal Intensive Care Unit Admission
Time frame: Followed for duration of neonatal hospital stay, estimated maximum 16 weeks
Number of Participants With Chorioamnionitis
Time frame: Duration of current pregnancy, anticipated maximum 18 weeks
Composite Neonatal Outcome
Time frame: Followed for duration of neonatal hospital stay, estimated maximum 16 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19037029Lyell DJ, Pullen KM, Mannan J, Chitkara U, Druzin ML, Caughey AB, El-Sayed YY. Maintenance nifedipine tocolysis compared with placebo: a randomized controlled trial. Obstet Gynecol. 2008 Dec;112(6):1221-1226. doi: 10.1097/AOG.0b013e31818d8386.
- Background: PubMed 22955308Likis FE, Edwards DR, Andrews JC, Woodworth AL, Jerome RN, Fonnesbeck CJ, McKoy JN, Hartmann KE. Progestogens for preterm birth prevention: a systematic review and meta-analysis. Obstet Gynecol. 2012 Oct;120(4):897-907. doi: 10.1097/AOG.0b013e3182699a15.
- Background: PubMed 21472815Hassan SS, Romero R, Vidyadhari D, Fusey S, Baxter JK, Khandelwal M, Vijayaraghavan J, Trivedi Y, Soma-Pillay P, Sambarey P, Dayal A, Potapov V, O'Brien J, Astakhov V, Yuzko O, Kinzler W, Dattel B, Sehdev H, Mazheika L, Manchulenko D, Gervasi MT, Sullivan L, Conde-Agudelo A, Phillips JA, Creasy GW; PREGNANT Trial. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2011 Jul;38(1):18-31. doi: 10.1002/uog.9017. Epub 2011 Jun 15.
- Background: PubMed 17671254Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH; Fetal Medicine Foundation Second Trimester Screening Group. Progesterone and the risk of preterm birth among women with a short cervix. N Engl J Med. 2007 Aug 2;357(5):462-9. doi: 10.1056/NEJMoa067815.
- Background: PubMed 18275573Borna S, Sahabi N. Progesterone for maintenance tocolytic therapy after threatened preterm labour: a randomised controlled trial. Aust N Z J Obstet Gynaecol. 2008 Feb;48(1):58-63. doi: 10.1111/j.1479-828X.2007.00803.x.
- Background: PubMed 22086108Arikan I, Barut A, Harma M, Harma IM. Effect of progesterone as a tocolytic and in maintenance therapy during preterm labor. Gynecol Obstet Invest. 2011;72(4):269-73. doi: 10.1159/000328719. Epub 2011 Nov 12.
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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.
George A Macones, MD, MSCE study chair
Washington University School of Medicine
Heather A Frey, MD, MSCI principal investigator
Ohio State University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Micronized progesterone suppository in people with Premature Birth and Obstetric Labor, Premature, run by Washington University School of Medicine at 1 site 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 4 inclusion and 11 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: stopped early, as of the sponsor's last update on 18 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jun 2019). 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?
Number of Participants Who Delivered Before 37 Weeks' (time frame: Duration of current pregnancy, anticipated maximum 18 weeks). 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 NCT01840228, which also lists 6 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 18 Jun 2019.