A Randomized Trial of Pessary in Singleton Pregnancies With a Short Cervix (TOPS)

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.

Study Overview

• Status: Terminated
• Conditions: Preterm Delivery; Short Cervix
• Intervention / Treatment: Device: Arabin Cervical Pessary

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 Type: Interventional
• Enrollment (Actual): 544
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama - Birmingham
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • New York
    • New York, New York, United States, 10032
      • Columbia University
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina - Chapel Hill
  • Ohio
    • Cleveland, Ohio, United States, 44109
      • Case Western Reserve University
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Magee Womens
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Brown University
  • Texas
    • Galveston, Texas, United States, 77555
      • University of Texas Medical Branch
    • Houston, Texas, United States, 77030
      • University of Texas - Houston
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.
• 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arabin Cervical Pessary; Arabin pessary. Participants will also receive vaginal progesterone to be administered daily, if it is the local standard of care.	Device: Arabin Cervical 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; Other Names: Arabin pessary
No Intervention: No Pessary; Participants will also receive vaginal progesterone to be administered daily, if it is the local standard of care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Before 37 weeks 0 days gestation, a period of up to 21 weeks from enrollment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Interval From Randomization to Delivery or Fetal Death	The median interval between randomization to delivery or death of the fetus.	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	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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)	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.	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.	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.	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.	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.	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.	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	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.	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.	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.	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.	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	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.	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.	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.	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.	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.	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.	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.	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.	delivery through hospital discharge (up to a length of 435 days)

Collaborators and Investigators

• Sponsor: The George Washington University Biostatistics Center
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Study Director: Monica Longo, MD, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Principal Investigator: Rebecca Clifton, Ph.D., George Washington University Biostatistics Center; Study Chair: Matthew Hoffman, MD, Christiana Care Health Services

Publications and helpful links

General Publications

• Iams 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.
• Hassan 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.
• Fonseca 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.
• Nicolaides KH, Syngelaki A, Poon LC, Picciarelli G, Tul N, Zamprakou A, Skyfta E, Parra-Cordero M, Palma-Dias R, Rodriguez Calvo J. A Randomized Trial of a Cervical Pessary to Prevent Preterm Singleton Birth. N Engl J Med. 2016 Mar 17;374(11):1044-52. doi: 10.1056/NEJMoa1511014.
• Goya M, Pratcorona L, Merced C, Rodo C, Valle L, Romero A, Juan M, Rodriguez A, Munoz B, Santacruz B, Bello-Munoz JC, Llurba E, Higueras T, Cabero L, Carreras E; Pesario Cervical para Evitar Prematuridad (PECEP) Trial Group. Cervical pessary in pregnant women with a short cervix (PECEP): an open-label randomised controlled trial. Lancet. 2012 May 12;379(9828):1800-6. doi: 10.1016/S0140-6736(12)60030-0. Epub 2012 Apr 3. Erratum In: Lancet. 2012 May 12;379(9828):1790.
• 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.
• Lawn 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.
• Romero 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.
• Owen J, Hankins G, Iams JD, Berghella V, Sheffield JS, Perez-Delboy A, Egerman RS, Wing DA, Tomlinson M, Silver R, Ramin SM, Guzman ER, Gordon M, How HY, Knudtson EJ, Szychowski JM, Cliver S, Hauth JC. Multicenter randomized trial of cerclage for preterm birth prevention in high-risk women with shortened midtrimester cervical length. Am J Obstet Gynecol. 2009 Oct;201(4):375.e1-8. doi: 10.1016/j.ajog.2009.08.015.
• Hui SY, Chor CM, Lau TK, Lao TT, Leung TY. Cerclage pessary for preventing preterm birth in women with a singleton pregnancy and a short cervix at 20 to 24 weeks: a randomized controlled trial. Am J Perinatol. 2013 Apr;30(4):283-8. doi: 10.1055/s-0032-1322550. Epub 2012 Aug 8.
• O'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.
• American 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.
• Meis 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. Erratum In: N Engl J Med. 2003 Sep 25;349(13):1299.
• da 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.
• Petrini 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.
• Andersen 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.
• Heath 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.
• Grobman 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.
• Norman 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. Erratum In: Lancet. 2019 Jan 19;393(10168):228. Lancet. 2019 Apr 20;393(10181):1596.
• 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.
• Society for Maternal-Fetal Medicine Publications Committee, with assistance of Vincenzo Berghella. Progesterone and preterm birth prevention: translating clinical trials data into clinical practice. Am J Obstet Gynecol. 2012 May;206(5):376-86. doi: 10.1016/j.ajog.2012.03.010. Erratum In: Am J Obstet Gynecol. 2013 Jan;208(1):86.
• Cahill AG, Odibo AO, Caughey AB, Stamilio DM, Hassan SS, Macones GA, Romero R. Universal cervical length screening and treatment with vaginal progesterone to prevent preterm birth: a decision and economic analysis. Am J Obstet Gynecol. 2010 Jun;202(6):548.e1-8. doi: 10.1016/j.ajog.2009.12.005. Epub 2010 Jan 15.
• Werner EF, Han CS, Pettker CM, Buhimschi CS, Copel JA, Funai EF, Thung SF. Universal cervical-length screening to prevent preterm birth: a cost-effectiveness analysis. Ultrasound Obstet Gynecol. 2011 Jul;38(1):32-7. doi: 10.1002/uog.8911. Epub 2011 May 24.
• Berghella V, Odibo AO, To MS, Rust OA, Althuisius SM. Cerclage for short cervix on ultrasonography: meta-analysis of trials using individual patient-level data. Obstet Gynecol. 2005 Jul;106(1):181-9. doi: 10.1097/01.AOG.0000168435.17200.53.
• Arabin B, Halbesma JR, Vork F, Hubener M, van Eyck J. Is treatment with vaginal pessaries an option in patients with a sonographically detected short cervix? J Perinat Med. 2003;31(2):122-33. doi: 10.1515/JPM.2003.017.
• Gyamfi-Bannerman C, Ananth CV. Trends in spontaneous and indicated preterm delivery among singleton gestations in the United States, 2005-2012. Obstet Gynecol. 2014 Dec;124(6):1069-1074. doi: 10.1097/AOG.0000000000000546. Erratum In: Obstet Gynecol. 2016 Mar;127(3):605.
• Committee opinion no 611: method for estimating due date. Obstet Gynecol. 2014 Oct;124(4):863-866. doi: 10.1097/01.AOG.0000454932.15177.be.
• Conde-Agudelo A, Romero R, Nicolaides K, Chaiworapongsa T, O'Brien JM, Cetingoz E, da Fonseca E, Creasy G, Soma-Pillay P, Fusey S, Cam C, Alfirevic Z, Hassan SS. Vaginal progesterone vs. cervical cerclage for the prevention of preterm birth in women with a sonographic short cervix, previous preterm birth, and singleton gestation: a systematic review and indirect comparison metaanalysis. Am J Obstet Gynecol. 2013 Jan;208(1):42.e1-42.e18. doi: 10.1016/j.ajog.2012.10.877. Epub 2012 Nov 15.
• Lan KK, Wittes J. The B-value: a tool for monitoring data. Biometrics. 1988 Jun;44(2):579-85.
• Stallones RA. The use and abuse of subgroup analysis in epidemiological research. Prev Med. 1987 Mar;16(2):183-94. doi: 10.1016/0091-7435(87)90082-x.
• Yusuf S, Wittes J, Probstfield J, Tyroler HA. Analysis and interpretation of treatment effects in subgroups of patients in randomized clinical trials. JAMA. 1991 Jul 3;266(1):93-8.
• Facco FL, Simhan HN. Short ultrasonographic cervical length in women with low-risk obstetric history. Obstet Gynecol. 2013 Oct;122(4):858-862. doi: 10.1097/AOG.0b013e3182a2dccd. Erratum In: Obstet Gynecol. 2014 May;123(5):1109.

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2017
• Primary Completion (Actual): April 2, 2022
• Study Completion (Actual): May 10, 2022

Study Registration Dates

• First Submitted: September 12, 2016
• First Submitted That Met QC Criteria: September 12, 2016
• First Posted (Estimated): September 15, 2016

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 16, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Pregnancy; Singletons; Short cervix; Pessary; Preterm delivery
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Premature Birth
• Other Study ID Numbers: HD36801 - TOPS; UG1HD087230 (U.S. NIH Grant/Contract); UG1HD027869 (U.S. NIH Grant/Contract); UG1HD040500 (U.S. NIH Grant/Contract); UG1HD034208 (U.S. NIH Grant/Contract); UG1HD027915 (U.S. NIH Grant/Contract); UG1HD040485 (U.S. NIH Grant/Contract); UG1HD053097 (U.S. NIH Grant/Contract); UG1HD040544 (U.S. NIH Grant/Contract); UG1HD040545 (U.S. NIH Grant/Contract); UG1HD040560 (U.S. NIH Grant/Contract); UG1HD040512 (U.S. NIH Grant/Contract); UG1HD087192 (U.S. NIH Grant/Contract); U24HD036801 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes