A Randomized Trial of Pessary in Singleton Pregnancies With a Short Cervix
Condition: Short Cervix; Preterm Delivery
MeSH terms: Premature Birth
Intervention: Arabin Cervical Pessary
Intervention description: 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
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention 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)
Enrollment: 544.0
Sex: Female
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Short cervix; Preterm delivery; Singletons; Pregnancy; Pessary

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.
    

Eligibility criteria:

        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.