Short CervixPhase 3TOPSNCT02901626
A Randomized Trial of Pessary in Singleton Pregnancies With a Short Cervix
A Phase 3 study testing Arabin Cervical Pessary in people with Short Cervix and Preterm Delivery, run by The George Washington University Biostatistics Center at 12 sites in United States.
Trial summary
The purpose of the study is to determine whether the Arabin pessary is a useful intervention of preterm birth at less than 37 weeks in women with a singleton gestation and a short cervix. Read more about this study
- Who is it for?
- Any age, women onlyHealthy volunteers can take part
- Conditions the study is for
- Short Cervix, Preterm Delivery
- What is being tested?
- Arabin Cervical Pessary
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 544 participants
- Where
- 12 sitesUnited States
- Study dates
- 14 Feb 2017to 10 May 2022
- Phase
- Phase 3
- 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 Any age
- Women only
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Singleton gestation. Twin gestation reduced to singleton either spontaneously or therapeutically, is not eligible unless the reduction occurred before 13 weeks 6 days project gestational age. Higher order multifetal gestations reduced to singletons are not eligible.
- Gestational age at randomization between 16 weeks 0 days and 23 weeks 6 days based on clinical information and evaluation of the earliest ultrasound.
- Cervical length on transvaginal examination of less than or equal to 20 mm by a study certified sonographer. There is no lower cervical length threshold.
Who cannot join
- Cervical dilation (internal os) 3 cm or greater on digital examination or evidence of prolapsed membranes beyond the external cervical os either at the time of the qualifying cervical ultrasound examination or at a cervical exam immediately before randomization.
- Fetal anomaly or imminent fetal demise. This includes lethal anomalies, or anomalies that may lead to early delivery or increased risk of neonatal death e.g., gastroschisis, spina bifida, serious karyotypic abnormalities. An ultrasound examination from 14 weeks 0 days to 23 weeks 6 days by project Estimated Date of Confinement (EDC) must be performed prior to randomization to evaluate the fetus for anomalies.
- Previous spontaneous preterm birth between 16 weeks 0 days and 36 weeks 6 days. This includes induction for pPROM in a prior pregnancy.
- Planned treatment with intramuscular 17-α hydroxy-progesterone caproate.
- Placenta previa, because of risk of bleeding and high potential for indicated preterm birth. A low lying placenta is acceptable.
- Active vaginal bleeding greater than spotting at the time of randomization, because of potential exacerbation due to pessary placement.
Show all 19Show fewer
- Symptomatic, untreated vaginal or cervical infection because of potential exacerbation due to pessary placement. Patients may be treated and if subsequently asymptomatic, randomized. However, if it is more than 10 days since the cervical length measurement, a new cervical length measurement must be obtained.
- Active, unhealed herpetic lesion on labia minora, vagina, or cervix due to the potential for significant patient discomfort or increasing genital tract viral spread. Once lesion(s) heal and the patient is asymptomatic, she may be randomized. History of herpes is not an exclusion.
- Rupture of membranes due to likelihood of pregnancy loss and preterm delivery as well as the risk of ascending infection which could be increased with pessary placement.
- More than six contractions per hour reported or documented prior to randomization. It is not necessary to place the patient on a tocodynamometer.
- Known major Mullerian anomaly of the uterus (specifically bicornuate, unicornuate, or uterine septum not resected) due to increased risk of preterm delivery which is unlikely to be affected by progesterone.
- Any fetal/maternal condition which would require invasive in-utero assessment or treatment, for example significant red cell antigen sensitization or neonatal alloimmune thrombocytopenia.
- Major maternal medical illness associated with increased risk for adverse pregnancy outcome or indicated preterm birth (treated hypertension requiring more than one agent, treatment for diabetes prior to pregnancy, chronic renal insufficiency defined by creatinine >1.4 mg/dL, carcinoma of the breast, conditions treated with chronic oral glucocorticoid therapy). Lupus, uncontrolled thyroid disease, and New York Heart Association(NYHA) stage II or greater cardiac disease are also excluded. Patients with seizure disorders, HIV, and other medical conditions not specifically associated with an increased risk of indicated preterm birth are not excluded. Prior cervical cone/LOOP/Loop Electrocautery Excision Procedure (LEEP) is not an exclusion criterion.
- Planned cerclage or cerclage already in place since it would preclude placement of a pessary.
- Planned indicated delivery prior to 37 weeks.
- Allergy to silicone.
- Participation in another interventional study that influences gestational age at delivery or neonatal morbidity or mortality.
- Participation in this trial in a previous pregnancy. Patients who were screened in a previous pregnancy, but not randomized, may be included.
- Prenatal care or delivery planned elsewhere unless the study visits can be made as scheduled and complete outcome information can be obtained.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
University of Alabama - Birmingham
Birmingham, Alabama, 35233
University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, 27599
Northwestern University
Chicago, Illinois, 60611
Case Western Reserve University
Cleveland, Ohio, 44109
Ohio State University
Columbus, Ohio, 43210
University of Texas Medical Branch
Galveston, Texas, 77555
University of Texas - Houston
Houston, Texas, 77030
Columbia University
New York, New York, 10032
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Magee Womens
Pittsburgh, Pennsylvania, 15213
Brown University
Providence, Rhode Island, 02905
University of Utah
Salt Lake City, Utah, 84132
About this study
The purpose of the study is to determine whether the Arabin pessary is a useful intervention of preterm birth at less than 37 weeks in women with a singleton gestation and a short cervix.
Read the detailed description
While cervical length is one of the most powerful predictors of subsequent preterm birth, the best treatment to reduce subsequent preterm birth remains unknown. This study is a randomized trial of women who have a singleton pregnancy and a short cervical length on transvaginal ultrasound as determined by a study-certified sonographer. It is being conducted at 12 clinical centers across the country and the recruitment target is enrollment of 850 pregnant women. Participants will be randomized to 1) Arabin pessary or 2) usual care as per by local hospital protocol. Pessary is a promising low-cost, non-surgical intervention that appears to be well-tolerated. The pessary will be placed by obstetric providers trained in appropriate placement of the Arabin pessary. The primary outcome of the study is delivery or fetal death prior to 37 weeks 0 days gestational age.
In the literature, there are two large trials that have produced conflicting results (M Goya et al, 2012, K Nicolaides et al, 2016). Thus, the results of an adequately powered and appropriately conducted trial from the United States will be important in determining whether pessary is a useful intervention for the prevention of subsequent preterm birth in women with singleton gestation.
- Conditions
- Short Cervix, Preterm Delivery
- Being tested
- Arabin Cervical Pessary
- Keywords
- Short cervix, Preterm delivery, Singletons, Pregnancy, Pessary
- Medical subject headings
- Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Arabin Cervical PessaryDevice
Also called Arabin pessary
The Arabin cervical pessary is a soft, flexible silicone pessary and fits high around the cervix with no rigid metal framework or inflexible edges that put increase pressure on the vaginal wall. It is available in a variety of sizes however three sizes will be used in this study:
Pessary Size upper diameter, lower diameter
- Nulliparous 65 mm, 32 mm
- Multiparous 70 mm, 32 mm
- Alternative 70 mm, 35 mm
| Study group | Role | What they receive |
|---|---|---|
| Arabin Cervical Pessary | Experimental | Arabin pessary. Participants will also receive vaginal progesterone to be administered daily, if it is the local standard of care. Receives: Device: Arabin Cervical Pessary |
| No Pessary | No intervention | Participants will also receive vaginal progesterone to be administered daily, if it is the local standard of care. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Preterm Delivery or Fetal Death at Less Than 37 Weeks.
Participants who either delivered or experienced a fetal death prior to 37 weeks gestation.
Measured: Before 37 weeks 0 days gestation, a period of up to 21 weeks from enrollment.
Secondary outcomes (33)
Interval From Randomization to Delivery or Fetal Death
The median interval between randomization to delivery or death of the fetus.
Measured: from randomization to delivery or fetal death (up to a length of 189 days)
Gestational Age at Delivery
Median gestational age (in weeks) at the time of delivery
Measured: From randomization to delivery (up to a length of 189 days)
Number of Participants With Preterm Delivery or Fetal Death at Less Than 28 Weeks Gestation
The number of participants who either delivered or experienced a fetal death prior to 28 weeks gestation.
Measured: from randomization to less than 28 weeks gestation (a period of less than 91 days)
Number of Participants With Preterm Delivery or Fetal Death at Less Than 32 Weeks Gestation
The number of participants who either delivered or experienced a fetal death prior to 32 weeks gestation.
Measured: from randomization to less than 32 weeks gestation (a period of less than 119 days)
Number of Participants With Preterm Delivery or Fetal Death at Less Than 35 Weeks Gestation
The number of participants who either delivered or experienced a fetal death prior to 35 weeks gestation.
Measured: from randomization to less than 35 weeks gestation (a period of less than 140 days)
Number of Participants With Preterm Premature Rupture of Membranes
Participants were categorized as yes if the amniotic membranes ruptured prior to labor onset and before 37 weeks gestation.
Measured: Before 37 weeks 0 days gestation, a period of up to 21 weeks from enrollment
Number of Participants With Spontaneous Preterm Delivery.
The number of participants who experienced spontaneous onset of labor and had an unassisted vaginal delivery prior to 37 weeks gestation. Induction for delivery was not performed and operative techniques such as forceps or vacuum were not used.
Measured: From randomization to delivery (up to a length of 189 days)
Number of Participants With Indicated Preterm Delivery
The number of participants who underwent labor induction or had an assisted vaginal delivery with forceps or vacuum or cesarean delivery prior to 37 weeks gestation.
Measured: from randomization to delivery (up to a length of 189 days)
Number of Participants With Cesarean Delivery
The number of participants who underwent a surgical procedure for delivery (cesarean) at any gestational age.
Measured: From randomization to delivery (up to a length of 189 days)
Number of Participants With Chorioamnionitis
The number of participants who had a clinical diagnosis of chorioamnionitis and a body temperature of at least 100.0° F (38° C) and no other defined infection.
Measured: From randomization to delivery (up to a length of 189 days)
Median Length of Maternal Antepartum Hospital Stay Before Delivery
Median number of days from maternal hospital admission for delivery and the date of delivery.
Measured: from date of admission for delivery up to delivery date (up to 5 days)
Number of Participants With Vaginal Infection
The number of participants with a clinical diagnosis of a vaginal infection. Includes participants with at least one study visit.
Measured: From randomization to delivery (up to a length of 189 days)
The Number of Participants Who Had a Vaginal Infection and Received Antibiotic Treatment, Among All Persons Enrolled With at Least One Study Visit
The number of participants who received antibiotics or antifungal medication for a vaginal infection (out of the total sample for which data is available)
Measured: From randomization to delivery (up to a length of 189 days)
Number of Participants Treated for Preterm Labor Including Placement of Cerclage
The number of participants who received any one of the following treatments for preterm labor: tocolysis, cerclage, bedrest, antenatal corticosteroids for fetal lung maturity, or magnesium sulfate for neuroprotection.
Measured: From randomization to delivery (up to a length of 189 days)
Median Duration of Neonatal Ventilator or Continuous Positive Airway Pressure Use
Median number of days a neonate or infant was on a ventilator or received continuous positive airway pressure.
Measured: delivery through hospital discharge (up to a length of 435 days)
Number of Neonates Requiring Ventilator or Continuous Positive Airway Pressure Use
The number of neonates or infants who required ventilator support or received continuous positive airway pressure.
Measured: delivery through hospital discharge (up to a length of 435 days)
Median Duration (in Days) of Neonatal Supplemental Oxygen Use
Median number of days a neonate received supplemental oxygen after admission to the NICU or intermediate nursery. Supplemental oxygen is defined as FiO2 > 0.21.
Measured: delivery through hospital discharge (up to a length of 435 days)
Number of Neonates With Seizures Requiring Treatment
The number of neonates with a clinical diagnosis of seizures who received anti-seizure medication.
Measured: delivery through hospital discharge (up to a length of 435 days)
Number of Neonates Small for Gestational Age < 5th Percentile
The number of neonates whose birthweight compared with gestational age at delivery was less than the 5th percentile, as assessed by sex and race, using United States birth certificate data.
Measured: delivery through hospital discharge (up to a length of 435 days)
Number of Neonates With Intraventricular Hemorrhage (IVH) Grades III or IV
IVH grades III or IV are as determined by cranial ultrasounds performed as part of routine clinical care and classified based on the Papile classification system
Measured: delivery through hospital discharge (up to a length of 435 days)
Number of Neonates With Retinopathy of Prematurity (ROP)
The number of neonates with a clinical diagnosis of retinopathy of prematurity where an ophthalmologic examination of the retina was performed.
Measured: delivery through hospital discharge (up to a length of 435 days)
Number of Neonates Experiencing Respiratory Distress Syndrome (RDS)
The number of neonates with a diagnosis of respiratory distress syndrome defined as the presence of clinical signs of respiratory distress (tachypnea, retractions, flaring, grunting, or cyanosis), with oxygen requirement and a chest x-ray that show hypoaeration and reticulogranular infiltrates.
Measured: delivery through hospital discharge (up to a length of 435 days)
Number of Neonates With Bronchopulmonary Dysplasia (BPD)
The number of neonates with a clinical diagnosis of bronchopulmonary dysplasia defined as oxygen requirement at 28 days of life if delivered at or after 32 weeks gestation, or at 36 weeks project gestational age if delivered before 32 weeks gestation.
Measured: Delivery through 28 days of life if delivered at or after 32 weeks. Delivery through 36 weeks gestation if delivered before 32 weeks.
Number of Neonates With Necrotizing Enterocolitis (NEC) Stage 2 or 3
The number of neonates diagnosed with NEC, defined as modified Bell Stage 2 or 3 where stage 2 represents clinical signs and symptoms with pneumatosis intestinalis on radiographs and stage 3 is defined as advanced clinical signs and symptoms, pneumatosis, impending or proven intestinal perforation.
Measured: delivery through hospital discharge (up to a length of 435 days)
Number of Neonates With Hyperbilirubinemia
The number of neonates diagnosed with hyperbilirubinemia, defined as peak total bilirubin of at least 15 mg% or the use of phototherapy
Measured: delivery through hospital discharge (up to a length of 435 days)
Neonatal Infectious Morbidity Including Sepsis, Suspected Sepsis and Pneumonia
The number of neonates diagnosed with any one of the following:
- Sepsis (within 72 hours and > 72 hours after birth) defined as a clinically ill infant in whom systemic infection is suspected with a positive blood, CSF, or catheterized/suprapubic urine culture; or, in the absence of positive cultures, clinical evidence of cardiovascular collapse or an unequivocal radiograph confirming infection.
- Suspected sepsis. The diagnosis of suspected sepsis will include infants with suspicious clinical findings of infection, but no positive cultures or radiographs.
- Pneumonia. The diagnosis of pneumonia will be confirmed by radiograph or positive blood culture.
Measured: delivery through hospital discharge (up to a length of 435 days)
Number of Neonates With Early Onset Sepsis
The number of neonates with a clinical diagnosis of sepsis within 72 hours of life, defined as a clinically ill infant in whom systemic infection is suspected with a positive blood, cerebrospinal fluid, or catheterized/suprapubic urine culture; or, in the absence of positive cultures, clinical evidence of cardiovascular collapse or an unequivocal radiograph confirming infection.
Measured: within 72 hours of birth
Number of Neonates With Late Onset Sepsis
The number of neonates with a clinical diagnosis of sepsis at or after 72 hours of life, defined as the presence of a clinically ill infant in whom systemic infection is suspected with a positive blood, cerebrospinal fluid, or catheterized/suprapubic urine culture; or, in the absence of positive cultures, clinical evidence of cardiovascular collapse or an unequivocal radiograph confirming infection.
Measured: 72 hours of birth or later (up to hospital discharge - a maximum of 435 days)
Number of Neonates With Suspected Sepsis
The number of neonates with suspicious clinical findings of infection, but no positive cultures or radiographs.
Measured: delivery through hospital discharge (up to a length of 435 days)
Number of Neonates With Pneumonia
The number of neonates with a clinical diagnosis of pneumonia within 72 hours of birth and confirmed by either an x-ray demonstrating consolidation with air bronchograms, or a positive blood culture performed at the time of clinical diagnosis.
Measured: delivery through hospital discharge (up to a length of 435 days)
Number of Neonates With Composite Outcome
The number of neonates diagnosed with any one of fetal or neonatal death or Respiratory Distress Syndrome, Grade 3 or 4 Intraventricular Hemorrhage, Periventricular Leukomalacia, Stage 2 or 3 Nectrotizing Enterocolitis, Bronchopulmonary Dysplasia, Stage III or higher Retinopathy of Prematurity, or early onset sepsis.
Measured: delivery through hospital discharge (up to a length of 435 days)
Median Length of Neonatal Hospital Stay
Median number of days the neonate/infant remained in hospital.
Measured: delivery through hospital discharge (up to a length of 435 days)
Median Number of Days in Neonatal Intensive Care Unit (NICU)
Median number of days the neonate/infant remained in the neonatal intensive care unit or special care nursery.
Measured: delivery through hospital discharge (up to a length of 435 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2016 (estimated)
- Study start14 Feb 2017
- Primary completion2 Apr 2022
- Study completion10 May 2022
Why it stopped: The study was stopped per the recommendation of the DSMB and NICHD.
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 (34)Papers the sponsor has linked to this study.
- Other trials for Short CervixStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The study is an unblinded randomized controlled trial. Participants will receive usual care (vaginal progesterone if they meet criteria per local standard of care) or an Arabin cervical pessary (plus progesterone if the local usual care is to receive vaginal progesterone for a short cervix).
- Masking
- None (open label)
- Enrolment
- 544 participants (actual)
Sponsor and investigators
- Lead sponsor
- The George Washington University Biostatistics Center
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Rebecca Clifton, Ph.D., Principal investigator, George Washington University Biostatistics CenterMonica Longo, MD, Study director, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)Matthew Hoffman, MD, Study chair, Christiana Care Health Services
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02901626
- Sponsor's protocol ID
- HD36801 - TOPS
- Other IDs
- UG1HD087230, UG1HD027915, UG1HD034208, UG1HD040500, UG1HD040485, UG1HD053097, UG1HD040544, UG1HD040545
- Acronym
- TOPS
- Status last verified
- Jun 2026
- First submitted
- 12 Sep 2016
- Last updated
- 23 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: The data will be shared after the completion of the trial and publication of the main analyses per NIH policy. Data will be available through the NICHD Data and Specimen Hub
Publications
Hamilton BE, Martin JA, Osterman MJ, Curtin SC, Matthews TJ. Births: Final Data for 2014. Natl Vital Stat Rep. 2015 Dec;64(12):1-64.
PubMed 26727629Lawn JE, Kerber K, Enweronu-Laryea C, Cousens S. 3.6 million neonatal deaths--what is progressing and what is not? Semin Perinatol. 2010 Dec;34(6):371-86. doi: 10.1053/j.semperi.2010.09.011.
PubMed 21094412American College of Obstetricians and Gynecologists; Committee on Practice Bulletins-Obstetrics. ACOG practice bulletin no. 127: Management of preterm labor. Obstet Gynecol. 2012 Jun;119(6):1308-17. doi: 10.1097/AOG.0b013e31825af2f0.
PubMed 22617615Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad AH, Spong CY, Hauth JC, Miodovnik M, Varner MW, Leveno KJ, Caritis SN, Iams JD, Wapner RJ, Conway D, O'Sullivan MJ, Carpenter M, Mercer B, Ramin SM, Thorp JM, Peaceman AM, Gabbe S; National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med. 2003 Jun 12;348(24):2379-85. doi: 10.1056/NEJMoa035140.
PubMed 12802023da Fonseca EB, Bittar RE, Carvalho MH, Zugaib M. Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study. Am J Obstet Gynecol. 2003 Feb;188(2):419-24. doi: 10.1067/mob.2003.41.
PubMed 12592250Petrini JR, Callaghan WM, Klebanoff M, Green NS, Lackritz EM, Howse JL, Schwarz RH, Damus K. Estimated effect of 17 alpha-hydroxyprogesterone caproate on preterm birth in the United States. Obstet Gynecol. 2005 Feb;105(2):267-72. doi: 10.1097/01.AOG.0000150560.24297.4f.
PubMed 15684150Andersen HF, Nugent CE, Wanty SD, Hayashi RH. Prediction of risk for preterm delivery by ultrasonographic measurement of cervical length. Am J Obstet Gynecol. 1990 Sep;163(3):859-67. doi: 10.1016/0002-9378(90)91084-p.
PubMed 2206073Iams JD, Goldenberg RL, Meis PJ, Mercer BM, Moawad A, Das A, Thom E, McNellis D, Copper RL, Johnson F, Roberts JM. The length of the cervix and the risk of spontaneous premature delivery. National Institute of Child Health and Human Development Maternal Fetal Medicine Unit Network. N Engl J Med. 1996 Feb 29;334(9):567-72. doi: 10.1056/NEJM199602293340904.
PubMed 8569824Heath VC, Southall TR, Souka AP, Elisseou A, Nicolaides KH. Cervical length at 23 weeks of gestation: prediction of spontaneous preterm delivery. Ultrasound Obstet Gynecol. 1998 Nov;12(5):312-7. doi: 10.1046/j.1469-0705.1998.12050312.x.
PubMed 9819868Fonseca 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 17671254O'Brien JM, Adair CD, Lewis DF, Hall DR, Defranco EA, Fusey S, Soma-Pillay P, Porter K, How H, Schackis R, Eller D, Trivedi Y, Vanburen G, Khandelwal M, Trofatter K, Vidyadhari D, Vijayaraghavan J, Weeks J, Dattel B, Newton E, Chazotte C, Valenzuela G, Calda P, Bsharat M, Creasy GW. Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2007 Oct;30(5):687-96. doi: 10.1002/uog.5158.
PubMed 17899572Hassan 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 21472815Romero R, Nicolaides K, Conde-Agudelo A, Tabor A, O'Brien JM, Cetingoz E, Da Fonseca E, Creasy GW, Klein K, Rode L, Soma-Pillay P, Fusey S, Cam C, Alfirevic Z, Hassan SS. Vaginal progesterone in women with an asymptomatic sonographic short cervix in the midtrimester decreases preterm delivery and neonatal morbidity: a systematic review and metaanalysis of individual patient data. Am J Obstet Gynecol. 2012 Feb;206(2):124.e1-19. doi: 10.1016/j.ajog.2011.12.003. Epub 2011 Dec 11.
PubMed 22284156Grobman WA, Thom EA, Spong CY, Iams JD, Saade GR, Mercer BM, Tita AT, Rouse DJ, Sorokin Y, Wapner RJ, Leveno KJ, Blackwell S, Esplin MS, Tolosa JE, Thorp JM Jr, Caritis SN, Van Dorsten JP; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network. 17 alpha-hydroxyprogesterone caproate to prevent prematurity in nulliparas with cervical length less than 30 mm. Am J Obstet Gynecol. 2012 Nov;207(5):390.e1-8. doi: 10.1016/j.ajog.2012.09.013. Epub 2012 Sep 17.
PubMed 23010094Norman JE, Marlow N, Messow CM, Shennan A, Bennett PR, Thornton S, Robson SC, McConnachie A, Petrou S, Sebire NJ, Lavender T, Whyte S, Norrie J; OPPTIMUM study group. Vaginal progesterone prophylaxis for preterm birth (the OPPTIMUM study): a multicentre, randomised, double-blind trial. Lancet. 2016 May 21;387(10033):2106-2116. doi: 10.1016/S0140-6736(16)00350-0. Epub 2016 Feb 24.
PubMed 26921136
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Trial of Pessary in Singleton Pregnancies With a Short Cervix
- ClinicalTrials.gov ID
- NCT02901626
- Acronym / sponsor ID
- TOPS / HD36801 - TOPS
- Conditions
- Short Cervix, Preterm Delivery
- Keywords
- Short cervix, Preterm delivery, Singletons, Pregnancy, Pessary
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was stopped per the recommendation of the DSMB and NICHD.
- Enrolment
- 544 participants (actual)
- Lead sponsor
- The George Washington University Biostatistics CenterUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 14 Feb 2017 (actual)
- Primary completion
- 2 Apr 2022 (actual)
- Study completion
- 10 May 2022 (actual)
- First posted
- 15 Sep 2016 (estimated)
- Results
- Posted 22 Jun 2023
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 the study is to determine whether the Arabin pessary is a useful intervention of preterm birth at less than 37 weeks in women with a singleton gestation and a short cervix.
Detailed description
While cervical length is one of the most powerful predictors of subsequent preterm birth, the best treatment to reduce subsequent preterm birth remains unknown. This study is a randomized trial of women who have a singleton pregnancy and a short cervical length on transvaginal ultrasound as determined by a study-certified sonographer. It is being conducted at 12 clinical centers across the country and the recruitment target is enrollment of 850 pregnant women. Participants will be randomized to 1) Arabin pessary or 2) usual care as per by local hospital protocol. Pessary is a promising low-cost, non-surgical intervention that appears to be well-tolerated. The pessary will be placed by obstetric providers trained in appropriate placement of the Arabin pessary. The primary outcome of the study is delivery or fetal death prior to 37 weeks 0 days gestational age.
In the literature, there are two large trials that have produced conflicting results (M Goya et al, 2012, K Nicolaides et al, 2016). Thus, the results of an adequately powered and appropriately conducted trial from the United States will be important in determining whether pessary is a useful intervention for the prevention of subsequent preterm birth in women with singleton gestation.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The study is an unblinded randomized controlled trial. Participants will receive usual care (vaginal progesterone if they meet criteria per local standard of care) or an Arabin cervical pessary (plus progesterone if the local usual care is to receive vaginal progesterone for a short cervix).
| Arm | Type | Receives |
|---|---|---|
| Arabin Cervical Pessary | Experimental | Device: Arabin Cervical PessaryArabin pessary. Participants will also receive vaginal progesterone to be administered daily, if it is the local standard of care. |
| No Pessary | No intervention | –Participants will also receive vaginal progesterone to be administered daily, if it is the local standard of care. |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Singleton gestation. Twin gestation reduced to singleton either spontaneously or therapeutically, is not eligible unless the reduction occurred before 13 weeks 6 days project gestational age. Higher order multifetal gestations reduced to singletons are not eligible.
- Gestational age at randomization between 16 weeks 0 days and 23 weeks 6 days based on clinical information and evaluation of the earliest ultrasound.
- Cervical length on transvaginal examination of less than or equal to 20 mm by a study certified sonographer. There is no lower cervical length threshold.
Key exclusion criteria (19 listed)
- Cervical dilation (internal os) 3 cm or greater on digital examination or evidence of prolapsed membranes beyond the external cervical os either at the time of the qualifying cervical ultrasound examination or at a cervical exam immediately before randomization.
- Fetal anomaly or imminent fetal demise. This includes lethal anomalies, or anomalies that may lead to early delivery or increased risk of neonatal death e.g., gastroschisis, spina bifida, serious karyotypic abnormalities. An ultrasound examination from 14 weeks 0 days to 23 weeks 6 days by project Estimated Date of Confinement (EDC) must be performed prior to randomization to evaluate the fetus for anomalies.
- Previous spontaneous preterm birth between 16 weeks 0 days and 36 weeks 6 days. This includes induction for pPROM in a prior pregnancy.
- Planned treatment with intramuscular 17-α hydroxy-progesterone caproate.
- Placenta previa, because of risk of bleeding and high potential for indicated preterm birth. A low lying placenta is acceptable.
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 |
|---|---|---|
| Arabin Cervical PessaryAlso: Arabin pessaryThe Arabin cervical pessary is a soft, flexible silicone pessary and fits high around the cervix with no rigid metal framework or inflexible edges that put increase pressure on the vaginal wall. It is available in a variety of sizes however three sizes will be used in this study: Pessary Size upper diameter, lower diameter 1. Nulliparous 65 mm, 32 mm 2. Multiparous 70 mm, 32 mm 3. Alternative 70 mm, 35 mm | Device | Arabin Cervical Pessary |
Primary outcome
Number of Participants With Preterm Delivery or Fetal Death at Less Than 37 Weeks.
Time frame: Before 37 weeks 0 days gestation, a period of up to 21 weeks from enrollment.
Participants who either delivered or experienced a fetal death prior to 37 weeks gestation.
33 secondary outcomes
Interval From Randomization to Delivery or Fetal Death
Time frame: from randomization to delivery or fetal death (up to a length of 189 days)
Gestational Age at Delivery
Time frame: From randomization to delivery (up to a length of 189 days)
Number of Participants With Preterm Delivery or Fetal Death at Less Than 28 Weeks Gestation
Time frame: from randomization to less than 28 weeks gestation (a period of less than 91 days)
Number of Participants With Preterm Delivery or Fetal Death at Less Than 32 Weeks Gestation
Time frame: from randomization to less than 32 weeks gestation (a period of less than 119 days)
Number of Participants With Preterm Delivery or Fetal Death at Less Than 35 Weeks Gestation
Time frame: from randomization to less than 35 weeks gestation (a period of less than 140 days)
Number of Participants With Preterm Premature Rupture of Membranes
Time frame: Before 37 weeks 0 days gestation, a period of up to 21 weeks from enrollment
Number of Participants With Spontaneous Preterm Delivery.
Time frame: From randomization to delivery (up to a length of 189 days)
Number of Participants With Indicated Preterm Delivery
Time frame: from randomization to delivery (up to a length of 189 days)
Number of Participants With Cesarean Delivery
Time frame: From randomization to delivery (up to a length of 189 days)
Number of Participants With Chorioamnionitis
Time frame: From randomization to delivery (up to a length of 189 days)
Median Length of Maternal Antepartum Hospital Stay Before Delivery
Time frame: from date of admission for delivery up to delivery date (up to 5 days)
Number of Participants With Vaginal Infection
Time frame: From randomization to delivery (up to a length of 189 days)
The Number of Participants Who Had a Vaginal Infection and Received Antibiotic Treatment, Among All Persons Enrolled With at Least One Study Visit
Time frame: From randomization to delivery (up to a length of 189 days)
Number of Participants Treated for Preterm Labor Including Placement of Cerclage
Time frame: From randomization to delivery (up to a length of 189 days)
Median Duration of Neonatal Ventilator or Continuous Positive Airway Pressure Use
Time frame: delivery through hospital discharge (up to a length of 435 days)
Number of Neonates Requiring Ventilator or Continuous Positive Airway Pressure Use
Time frame: delivery through hospital discharge (up to a length of 435 days)
Median Duration (in Days) of Neonatal Supplemental Oxygen Use
Time frame: delivery through hospital discharge (up to a length of 435 days)
Number of Neonates With Seizures Requiring Treatment
Time frame: delivery through hospital discharge (up to a length of 435 days)
Number of Neonates Small for Gestational Age < 5th Percentile
Time frame: delivery through hospital discharge (up to a length of 435 days)
Number of Neonates With Intraventricular Hemorrhage (IVH) Grades III or IV
Time frame: delivery through hospital discharge (up to a length of 435 days)
Number of Neonates With Retinopathy of Prematurity (ROP)
Time frame: delivery through hospital discharge (up to a length of 435 days)
Number of Neonates Experiencing Respiratory Distress Syndrome (RDS)
Time frame: delivery through hospital discharge (up to a length of 435 days)
Number of Neonates With Bronchopulmonary Dysplasia (BPD)
Time frame: Delivery through 28 days of life if delivered at or after 32 weeks. Delivery through 36 weeks gestation if delivered before 32 weeks.
Number of Neonates With Necrotizing Enterocolitis (NEC) Stage 2 or 3
Time frame: delivery through hospital discharge (up to a length of 435 days)
Number of Neonates With Hyperbilirubinemia
Time frame: delivery through hospital discharge (up to a length of 435 days)
Neonatal Infectious Morbidity Including Sepsis, Suspected Sepsis and Pneumonia
Time frame: delivery through hospital discharge (up to a length of 435 days)
Number of Neonates With Early Onset Sepsis
Time frame: within 72 hours of birth
Number of Neonates With Late Onset Sepsis
Time frame: 72 hours of birth or later (up to hospital discharge - a maximum of 435 days)
Number of Neonates With Suspected Sepsis
Time frame: delivery through hospital discharge (up to a length of 435 days)
Number of Neonates With Pneumonia
Time frame: delivery through hospital discharge (up to a length of 435 days)
Number of Neonates With Composite Outcome
Time frame: delivery through hospital discharge (up to a length of 435 days)
Median Length of Neonatal Hospital Stay
Time frame: delivery through hospital discharge (up to a length of 435 days)
Median Number of Days in Neonatal Intensive Care Unit (NICU)
Time frame: delivery through hospital discharge (up to a length of 435 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 26727629Hamilton BE, Martin JA, Osterman MJ, Curtin SC, Matthews TJ. Births: Final Data for 2014. Natl Vital Stat Rep. 2015 Dec;64(12):1-64.
- Background: PubMed 21094412Lawn JE, Kerber K, Enweronu-Laryea C, Cousens S. 3.6 million neonatal deaths--what is progressing and what is not? Semin Perinatol. 2010 Dec;34(6):371-86. doi: 10.1053/j.semperi.2010.09.011.
- Background: PubMed 22617615American College of Obstetricians and Gynecologists; Committee on Practice Bulletins-Obstetrics. ACOG practice bulletin no. 127: Management of preterm labor. Obstet Gynecol. 2012 Jun;119(6):1308-17. doi: 10.1097/AOG.0b013e31825af2f0.
- Background: PubMed 12802023Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad AH, Spong CY, Hauth JC, Miodovnik M, Varner MW, Leveno KJ, Caritis SN, Iams JD, Wapner RJ, Conway D, O'Sullivan MJ, Carpenter M, Mercer B, Ramin SM, Thorp JM, Peaceman AM, Gabbe S; National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med. 2003 Jun 12;348(24):2379-85. doi: 10.1056/NEJMoa035140.
- Background: PubMed 12592250da Fonseca EB, Bittar RE, Carvalho MH, Zugaib M. Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study. Am J Obstet Gynecol. 2003 Feb;188(2):419-24. doi: 10.1067/mob.2003.41.
- Background: PubMed 15684150Petrini JR, Callaghan WM, Klebanoff M, Green NS, Lackritz EM, Howse JL, Schwarz RH, Damus K. Estimated effect of 17 alpha-hydroxyprogesterone caproate on preterm birth in the United States. Obstet Gynecol. 2005 Feb;105(2):267-72. doi: 10.1097/01.AOG.0000150560.24297.4f.
- Background: PubMed 2206073Andersen HF, Nugent CE, Wanty SD, Hayashi RH. Prediction of risk for preterm delivery by ultrasonographic measurement of cervical length. Am J Obstet Gynecol. 1990 Sep;163(3):859-67. doi: 10.1016/0002-9378(90)91084-p.
- Background: PubMed 8569824Iams JD, Goldenberg RL, Meis PJ, Mercer BM, Moawad A, Das A, Thom E, McNellis D, Copper RL, Johnson F, Roberts JM. The length of the cervix and the risk of spontaneous premature delivery. National Institute of Child Health and Human Development Maternal Fetal Medicine Unit Network. N Engl J Med. 1996 Feb 29;334(9):567-72. doi: 10.1056/NEJM199602293340904.
- Background: PubMed 9819868Heath VC, Southall TR, Souka AP, Elisseou A, Nicolaides KH. Cervical length at 23 weeks of gestation: prediction of spontaneous preterm delivery. Ultrasound Obstet Gynecol. 1998 Nov;12(5):312-7. doi: 10.1046/j.1469-0705.1998.12050312.x.
- 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 17899572O'Brien JM, Adair CD, Lewis DF, Hall DR, Defranco EA, Fusey S, Soma-Pillay P, Porter K, How H, Schackis R, Eller D, Trivedi Y, Vanburen G, Khandelwal M, Trofatter K, Vidyadhari D, Vijayaraghavan J, Weeks J, Dattel B, Newton E, Chazotte C, Valenzuela G, Calda P, Bsharat M, Creasy GW. Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2007 Oct;30(5):687-96. doi: 10.1002/uog.5158.
- 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.
- Individual participant dataSharing planned: Yes. The data will be shared after the completion of the trial and publication of the main analyses per NIH policy. Data will be available through the NICHD Data and Specimen Hub
Related trials for Short Cervix
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
Not yet recruitingPhase 4
Azithromycin for Cerclage Prophylaxis
Cervical Insufficiency
Recruiting
Microbiological and Biochemical Profiling of Amniotic Fluid in Women With Short Cervix or Premature Rupture of Membranes
Short Cervix, PROM, Preterm (Pregnancy)
Recruiting
LATe Cerclage in High-risk Pregnancies (LATCH)
Premature Birth
Not yet recruiting
Bed Rest With a Short Cervix on Preterm Birth
Preterm Birth, Cervical Insufficiency
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.
Rebecca Clifton, Ph.D. principal investigator
George Washington University Biostatistics Center
Monica Longo, MD study director
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Matthew Hoffman, MD study chair
Christiana Care Health Services
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Arabin Cervical Pessary in people with Short Cervix and Preterm Delivery, run by The George Washington University Biostatistics Center at 12 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 3 inclusion and 19 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 23 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 22 Jun 2023). 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 With Preterm Delivery or Fetal Death at Less Than 37 Weeks. (time frame: Before 37 weeks 0 days gestation, a period of up to 21 weeks from enrollment.). 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 NCT02901626, which also lists 34 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 23 Jun 2026.