A Trial of Pessary and Progesterone for Preterm Prevention in Twin Gestation With a Short Cervix


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Trial ID: NCT02518594


This protocol outlines a randomized trial of 630 women evaluating the use of micronized vaginal progesterone or pessary versus control (placebo) to prevent early preterm birth in women carrying twins and with a cervical length of less than 30 millimeters.

Official Title

A Randomized Trial of Pessary and Progesterone for Preterm Prevention in Twin Gestation With a Short Cervix

Stanford Investigator(s)

Yasser El-Sayed, Professor
Yasser El-Sayed, Professor

Charles B. and Ann L. Johnson Professor in the School of Medicine and Professor, by courtesy, of Pediatrics (Neonatology) and of Surgery


Inclusion Criteria:

   1. Twin gestation with cardiac activity in both fetuses. Higher order multifetal
   gestations reduced to twins, either spontaneously or therapeutically, are not eligible
   unless the reduction occurred by 13 weeks 6 days project gestational age.

   2. Gestational age at randomization between 16 weeks 0 days and 23 weeks 6 days based on
   clinical information and evaluation of the earliest ultrasound.

   3. Cervical length on transvaginal examination of less than 30 mm by a study certified

Exclusion Criteria:

   1. 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. There is no lower threshold of cervical length measurement threshold on
   ultrasound that is an exclusion criterion.

   2. Monoamniotic gestation, due to increased risk of adverse pregnancy outcome

   3. Twin-twin transfusion syndrome, due to increased risk of adverse pregnancy outcome

   4. Evidence of severe IUGR (intrauterine growth restriction) (<5th percentile for
   gestational age) in either fetus

   5. Fetal anomaly in either twin 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 EDC (estimated date of
   conception) must be performed prior to randomization to evaluate the fetuses for

   6. Placenta previa, because of risk of bleeding and high potential for indicated preterm

   7. Active vaginal bleeding greater than spotting at the time of randomization, because of
   potential exacerbation due to pessary placement.

   8. Symptomatic, untreated vaginal or cervical infection, also because of potential
   exacerbation due to pessary placement. Patients may be treated and if subsequently
   asymptomatic, randomized.

   9. 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.

10. 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

11. More than six contractions per hour reported or documented prior to randomization. It
   is not necessary to place the patient on a tocodynamometer

12. 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

13. Any fetal/maternal condition which would require invasive in-utero assessment or
   treatment, for example significant red cell antigen sensitization or neonatal
   alloimmune thrombocytopenia

14. Major maternal medical illness associated with increased risk for adverse pregnancy
   outcome or indicated preterm birth (treated hypertension requiring more than one
   agent, pre-gestational treatment for diabetes prior to pregnancy, chronic renal
   insufficiency failure defined by creatinine >1.4 mg/dL, carcinoma of the breast,
   conditions treated with chronic oral glucocorticoid therapy. Specifically, 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/LEEP is not an exclusion criterion.

15. Planned cerclage or cerclage already in place since it would preclude placement of a

16. Planned indicated delivery prior to 35 weeks

17. Planned or actual progesterone treatment of any type or form after 15 weeks 6 days
   during the current pregnancy

18. Allergy to progesterone, silicone, or excipients in the study drug, including peanuts
   or peanut oil in the study drug or placebo

19. Known, suspected or history of breast cancer because breast cancer is a
   contraindication to the active study medication.

20. Known liver dysfunction or disease because liver disease is a contraindication to the
   active study medication.

21. Participation in another interventional study that influences gestational age at
   delivery or neonatal morbidity or mortality

22. Participation in this trial in a previous pregnancy. Patients who were screened in a
   previous pregnancy, but not randomized, do not have to be excluded.

23. Prenatal care or delivery planned elsewhere unless the study visits can be made as
   scheduled and complete outcome information can be obtained


drug: Vaginal progesterone

drug: Placebo

device: Arabin Pessary


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Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Cynthia Willson, RN BSN