Clinical trial NCT01519765: Buccal Versus Vaginal Misoprostol for Third Trimester Induction of Labor
Official title: Buccal Versus Vaginal Misoprostol for Third Trimester Induction of Labor: Randomized Control Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Pregnancy
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
First posted: 2012-01-27
Enrollment: 73
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Approximately 22% of term pregnancies are induced. Misoprostol, a prostaglandin E1 analogue, is a widely accepted induction agent, that has been proven safe and effective for induction of labor. It stimulates both cervical ripening and uterine contractions, thus making it an ideal induction agent for unfavorable cervices. Research has examined the pharmacokinetics of different administration routes and effects on uterine contractility, side effects, and safety. Vaginal misoprostol has been shown to be superior over oral administration however patients often prefer a more tolerable route. Buccal administration has already been shown to be as effective as vaginal misoprostol for cervical ripening and induction in both first trimester and second trimester abortions. There is minimal research comparing buccal versus vaginal for third trimester induction of labor. The investigators study is a prospective, double blinded, randomized control trial comparing vaginal misoprostol and buccal misoprostol in equal dosages of 25 mcg. The investigators seek to answer the question whether buccal misoprostol is as effective as vaginal misoprostol for third trimester induction of labor.

Detailed description: Design Overview This will be a prospective, double blind, randomized, placebo-controlled trial comparing buccal versus vaginal misoprostol in equal doses (25 mcg every 4 hours). Each participant will receive one buccal and one vaginal tablet, only one containing misoprostol. The administration will be repeated every four hours if contractions are inadequate (frequency less than every 5 minutes) until the cervix is favorable, spontaneous rupture of membranes occurs, or the patient is in active labor. Patient will be continued on intermittent fetal heart monitoring 1 hour after administration. Prior to discharge women in the study will be asked to complete a questionnaire as to their preferences of route of administration and side effects.

1. Recruitment, Consenting, and Confirming Eligibility: Women with obstetric, medical, or psychosocial indications of induction of labor at University of California, Los Angeles Ronald Reagan Medical Center will be evaluated for participation. Those who meet eligibility criteria will be invited to participate. The subject will be counseled about the study, and if interested, will undergo the consent process. Each potential subject will receive a thorough overview of the study protocol and will review the consent form with study staff. All questions will be answered. The subject will be advised that a decision not to participate in the study will not affect the quality or availability of medical services she will receive at the hospital. She will also be advised that she can stop participating in the study at any time, for any reason, and that this will not impact the services she receives. If the subject elects to participate, two copies of the consent will be signed by the subject and research staff. A signed consent, along with a copy of the Experimental Subjects Bill of Rights, will be given to the subject. The other consent will be filed in a locked file cabinet.

   A general medical and gynecological history and physical will be done as is standard of care. Routine obstetric labs and any other medically indicated labs will be sent as is standard of care. Patients will undergo a non-stress test and uterine contraction monitoring prior to induction of labor. Obstetrical ultrasound will be reviewed or performed if indicated per the physician. Assessment of the cervix and Bishop score, pelvis, fetal size, and presentation will be performed. An unfavorable cervix is defined as Bishop score of 6 or less (ACOG). Women with ruptured membranes will not be able to participate. Gestational age will be determined on the basis of last menstrual period, confirmed by earliest ultrasound, or a corrected estimated date of confinement by the earliest ultrasound.
2. Misoprostol Administration/ Evaluation: The subject will be randomized to either of two groups. Each participant will receive both a vaginal and buccal tablet, with one tablet containing misoprostol. Subjects will be instructed by a nurse regarding buccal placement and to swallow any residue remaining after 20 minutes.

   Intravaginal administration of pill will be performed by a resident Physician or midwife. The subject will remain recumbent for at least 30 minutes. The subject will undergo fetal heart rate (FHR) and uterine contraction monitoring for at least 1 hour after misoprostol administration. The subject may undergo further FHR and uterine contraction monitoring per physician discretion. If the subject does not have adequate uterine contractions (uterine contraction occurring at least every 5 minutes), the same dosage and route of administration regimen will be repeated to 6 maximum dosage (maximum of 150mcg). Cervical assessment of Bishop score will be performed with each treatment during vaginal administration.

   Treatment will continue until spontaneous rupture of membranes, active labor, or favorable cervix (Bishop \>6). Augmentation of labor using pitocin may start after 4 hours of last misoprostol dose according to routine protocol. Amniotomy may be performed at the discretion of the managing obstetrician. If labor is not achieved after receiving 150mcg of misoprostol, it will be categorized as a failed induction. At this time, the subject may be offered oxytocin induction, foley bulb mechanical dilation, or cesarean section, according to the fetal and participant condition. Terbutaline 0.25mg subcutaneous may be given for tachysystole (5 uterine contractions in 10 minutes) with FHR changes or FHR category II-III changes (minimal variability, prolonged deceleration, repetitive variables, sinusoidal pattern, repetitive late deceleration) that are not responsive to resuscitative measures ( oxygen supplementation, side positioning, intravenous fluids) according to physician's discretion.
3. Follow up: A short survey questionnaire assessing gastrointestinal side effects, experiences, and preferences of route of administration will be given prior to discharge.

Eligibility criteria: Inclusion Criteria:

* Willingness to participate / consent in a placebo-controlled trial
* Age 18 and older
* Pregnancy between 34 and 42 years of gestation
* Admitted for labor induction because of either medical, obstetric, or psychosocial indications
* Live singleton fetus
* Bishop score less than or equal to six
* Cephalic presentation
* Reactive non-stress test or Negative contraction test

Exclusion Criteria:

* Premature rupture of membranes
* Multiparity \> 5
* Contraindication to vaginal or labor delivery
* Suspected placental abruption
* Significant hepatic, renal or cardiac disease
* Known hypersensitivity to misoprostol or prostaglandin analogue
* Recent prostaglandin administration for induction of labor
* Multifetal pregnancy
* Macrosomia \> 4500g estimated fetal weight by ultrasound or leopold

Primary outcomes:
measure: Vaginal Delivery Within 24 Hours of Labor Induction
timeFrame: Within 24 hours of labor induction
Secondary outcomes:
measure: Time to Vaginal Delivery
timeFrame: Start of induction until vaginal delivery
measure: Time to Delivery
timeFrame: Until delivery
measure: Time to Active Labor
timeFrame: Until active labor
measure: Rates of Vaginal Delivery
timeFrame: Until delivery
measure: Cesarean Delivery Rate
timeFrame: Until delivery
measure: Number of Misoprostol Doses
timeFrame: Until delivery
measure: Arrest of Dilation
timeFrame: Until delivery
measure: Failed Induction of Labor
timeFrame: Until delivery
measure: Pitocin
timeFrame: Until delivery
measure: Foley Bulb
timeFrame: Until delivery
measure: Artificial Rupture of Membranes (AROM)
timeFrame: Until delivery
measure: Abnormal Fetal Heart Tracing (FHT)
timeFrame: Until 4 hours of last misoprostol dose
measure: Tachysystole With Abnormal FHT
timeFrame: Until 4 hours after last misoprostol dose
measure: Tachysystole
timeFrame: Until 4 hours after last misoprostol dose
measure: Neonatal Intensive Care Unit (NICU) Admission
timeFrame: Until discharge from hospital
measure: Meconium
timeFrame: Until delivery
measure: Chorioamnionitis
timeFrame: Until 48 hours after delivery
measure: APGARS
timeFrame: 5 minutes after delivery
measure: Patient Satisfaction With Buccal Versus Vaginal Misoprostol Administration.
timeFrame: Until 72 hours after delivery
measure: Patient Preference
timeFrame: Until 72 hours after delivery
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
Study officials:
affiliation: Associate Clinical Professor
name: Ram Parvataneni, MD
role: PRINCIPAL_INVESTIGATOR
References: