Short Cervical Length Clinical Trial
— PROSPECTOfficial title:
A Randomized Trial of Pessary and Progesterone for Preterm Prevention in Twin Gestation With a Short Cervix
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.
| Status | Recruiting |
| Enrollment | 630 |
| Est. completion date | April 30, 2025 |
| Est. primary completion date | March 31, 2025 |
| Accepts healthy volunteers | No |
| Gender | Female |
| Age group | N/A and older |
| Eligibility | 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 sonographer. 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 anomalies. 6. Placenta previa, because of risk of bleeding and high potential for indicated preterm birth 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 pessary 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 |
| Country | Name | City | State |
|---|---|---|---|
| United States | University of Alabama - Birmingham | Birmingham | Alabama |
| United States | University of North Carolina - Chapel Hill | Chapel Hill | North Carolina |
| United States | Northwestern University-Prentice Hospital | Chicago | Illinois |
| United States | Case Western Reserve University | Cleveland | Ohio |
| United States | Ohio State University | Columbus | Ohio |
| United States | University of Colorado | Denver | Colorado |
| United States | Duke University | Durham | North Carolina |
| United States | University of Texas - Galveston | Galveston | Texas |
| United States | Baylor College of Medicine | Houston | Texas |
| United States | University of Texas - Houston | Houston | Texas |
| United States | Columbia University | New York | New York |
| United States | Hospital of the University of Pennsylvania | Philadelphia | Pennsylvania |
| United States | Magee Women's Hospital | Pittsburgh | Pennsylvania |
| United States | Brown University | Providence | Rhode Island |
| United States | University of Utah Medical Center | Salt Lake City | Utah |
| United States | The Regents of the University of California, San Francisco | San Francisco | California |
| Lead Sponsor | Collaborator |
|---|---|
| The George Washington University Biostatistics Center | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Delivery or fetal loss of either twin prior to 35 weeks gestation | Preterm delivery or fetal loss prior to 35 weeks gestation | prior to 35 weeks gestation | |
| Secondary | Interval from randomization to delivery (or fetal demise) | Randomization may begin at 16 weeks, and most patients will be delivered by 41 weeks | Randomization to delivery can be up to 26 weeks | |
| Secondary | Gestational age at delivery | Gestational age at the time of delivery. Randomization begins at 16 weeks gestation | Randomization to delivery can be up to 26 weeks | |
| Secondary | Preterm delivery or fetal demise of either twin prior to 28 weeks gestation, 32 weeks gestation, and 37 weeks gestation | Preterm delivery or fetal loss of either twin prior to 28 weeks gestation; prior to 32 weeks gestation; and prior to 37 weeks gestation | From randomization to up to 37 weeks gestation (up to 21 weeks) | |
| Secondary | Spontaneous preterm delivery (following preterm labor or pPROM) < 35 weeks gestation and < 32 weeks gestation | Spontaneous preterm delivery before 35 weeks gestation and 32 weeks gestation | From randomization to delivery (up to 19 weeks) | |
| Secondary | Indicated preterm delivery < 35 weeks | Preterm delivery prior to 35 weeks gestation with medical indications | From randomization to delivery (up to 19 weeks) | |
| Secondary | Cesarean delivery | Delivery by cesarean | Randomization to delivery can be up to 26 weeks | |
| Secondary | Fetal or neonatal death | Fetal or neonatal death | Up to 28 days postnatal age | |
| Secondary | Small for gestational age | Less than 5th percentile weight for gestational age, by sex and race of the infant based on United States birth certificate data | Randomization to delivery can be up to 26 weeks | |
| Secondary | Composite neonatal outcome | Fetal or neonatal death, RDS, grade III or IV IVH, PVL, Stage 2 or 3 NEC, BPD, Stage III or higher ROP, or early onset sepsis | Birth to neonatal discharge or death, whichever is first (up to 6 weeks) | |
| Secondary | Length of hospital stay, need for NICU or intermediate care admission and length of stay if admitted | Length of hospital stay in days, any Neonatal ICU or intermediate care admission, or length of hospital or intermediate care stay in days | Birth to neonatal discharge or death, whichever is first (up to 6 weeks) |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT01954095 -
The Impact of Vaginal and IM Progestins on the Cervix
|
N/A |