Vaginal Progesterone to Reduce the Risk of Another Preterm Birth
A Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center Study to Assess the Efficacy, Safety, and Tolerability of 8% Progesterone Vaginal Gel in Preventing Preterm Delivery in Pregnant Women at Increased-Risk for Preterm Delivery
This research study is being conducted at over 12 pregnancy research centers in the US. The study will compare an investigational treatment with a placebo (a treatment without medication). Neither the investigators nor the patients in the trial will know which treatment has been assigned. All study medications will be given vaginally once a day. Treatment will begin before pregnancy week 23 and will continue until the end of pregnancy week 36.
Patients who participate are to have:
A single baby pregnancy (no twins or triplets allowed)
Patients will start treatment before pregnancy week 23
Patients must have a previous preterm birth (a "preemie")
Patients must be 18-45 years of age
Progesterone 8% Vaginal gel, once daily, maximum duration from 18 07 weeks gestation to 37 0/7 weeks gestation
Placebo vaginal gel, once daily, maximum duration from 18 07 weeks gestation to 37 0/7 weeks gestation
Inclusion Criteria: The subject has a history of a documented spontaneous singleton preterm delivery (hospital or clinic record, letter from healthcare provider, or birth certificate) from 20 0/7 to 35 0/7 weeks gestational age with the immediate preceding pregnancy or has a cervical length of 2.5 cm or less measured by transvaginal ultrasound with the current pregnancy. "Spontaneous preterm delivery" is a delivery (<35 weeks), either vaginal or cesarean, that is initiated by either preterm PROM followed by contractions or preterm labor initiated with in-tact membranes. A previous preterm delivery secondary to an incompetent cervix where a cerclage is considered for this pregnancy is not considered a preterm delivery (please see Exclusion Criteria No. 10). Subjects enrolled based on a history of preterm delivery may have had a pregnancy loss (or losses) at <20 0/7 weeks gestational age between the preceding preterm delivery and the current pregnancy. The female subject is between 18 and 45 years of age at the time of screening. The pregnancy has an estimated gestational age between 16 0/7 weeks and 22 6/7 weeks. The subject speaks either English or a common local language. The subject has voluntarily signed the Informed Consent Form and associated forms after having the contents explained, and all her questions are answered to her satisfaction and understanding. In the opinion of the investigator, the subject is able to understand the study and is able to give informed consent, as well as participate in it and adhere to study procedures. Exclusion Criteria: The subject has a previous history of an adverse reaction to progesterone or any component present in Prochieve® 8% vaginal gel. The subject has been treated with a progestogen within the previous 4 weeks. The subject is currently being treated for a seizure disorder, has an unstable psychiatric disorder, is taking antihypertensive therapy for chronic hypertension at the time of enrollment, has a history of congestive heart failure or chronic renal failure, or has uncontrolled diabetes mellitus (known end-organ dysfunction secondary to vascular disease). The subject has active thrombophlebitis or a thromboembolic disorder, or a history of hormone-associated thrombophlebitis or thromboembolic disorders. The subject has liver dysfunction or disease. The subject has known or suspected malignancy of the breast or genital organs. The subject is currently participating in another investigational study or has participated in an investigational drug study within one month prior to screening for this study. The subject's current pregnancy is complicated by a major fetal anomaly or known chromosomal abnormality. The subject has a uterine anatomic malformation (bicornuate uterus, septate uterus) The subject has a multifetal gestation. The subject has a cervical cerclage in place or has plans to have one placed during the current pregnancy. The subject, in the judgment of the investigator, will be unable or unwilling to comply with study-related assessments and procedures. The subject currently has preterm rupture of membranes, vaginal bleeding, known or suspected amnionitis, or signs or symptoms of preterm labor at the time of enrollment. The subject is HIV positive with a CD4 count of _<350 cells/mm3 and is receiving more than 1 medication to prevent the transfer of AIDS to the fetus. The subject has placenta previa or a low-lying placenta. The subject will be considered for the study if she is not at risk for increased bleeding and has not been given any vaginal precautions. The subject's qualifying preterm delivery was an indicated delivery without preterm labor (i.e. delivery performed for fetal distress, maternal eclampsia/preeclampsia, fetal death, or amnionitis in the absence of contractions).