Clinical Trial: A Randomized Trial of Two Regimens of Misoprostol for Second Trimester Termination for Intrauterine Fetal Death

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Randomized Trial of Two Regimens of Misoprostol for Second Trimester Intrauterine Fetal Death

Brief Summary:

Misoprostol (Cytotec®) is a synthetic prostaglandin E1 analog that has been marketed in the United States since 1988 as a gastric cytoprotective agent. Despite a focused campaign by the manufacturer to curtail its use in obstetric practice, misoprostol has, over the past several years, gained widespread acceptance to effect the medical termination of pregnancy in the second trimester, either alone or after pretreatment with mifepristone. The primary reasons for this prompt incorporation into standard practice include its low cost and the lack of stringent storage requirements.

Vaginal administration seems to be more efficacious than when given orally. The use of sublingual misoprostol for first trimester abortions has been extensively investigated as evidenced by the large number of publications comparing sublingual to other routes of misoprostol for first trimester pregnancy termination, on the assumption that the sublingual route would have a similar efficacy of the vaginal route. In addition, the sublingual route would combine an easier administration with the added advantage of no restriction of mobility after administration. There has been no previous report in the literature comparing the use of misoprostol given sublingually to that given vaginally for the second trimester termination following intrauterine fetal death. Our aim is to compare efficacy, safety and patient satisfaction with misoprostol given vaginally (the current standard) to that given sublingually.


Detailed Summary:

Prostaglandins have been recognized as effective abortifacients for several decades. Misoprostol, a synthetic analogue of prostaglandin E1, has several advantages over other prostaglandins that include low cost, easy storage at room temperature, and favorable side effect profile. In recent years, misoprostol has attracted attention as an effective and cost-efficient agent for the medical interruption of the second-trimester pregnancy. Nowadays, misoprostol has been accepted widely as a safe and effective agent for labor induction during the second trimester. Various doses, routes, and protocols for medical termination of pregnancy during the second trimester have been investigated. The optimal dosage and route of administration, however, have yet to be defined. Previous studies have demonstrated greater efficacy with vaginal misoprostol versus oral administration in effecting mid-trimester termination. However, oral administration of any medication is preferred by patients and health care providers alike. The higher efficacy after vaginal administration may be explained by the pharmacokinetics of the drug. Zeiman et al showed that the systemic bioavailability of vaginally administered misoprostol is 3 times higher than that after oral administration. Plasma concentrations of its metabolite, misoprostol acid, peak one to two hours after vaginal application as compared with the peak seen 30 minutes following oral administration, and although peak levels are lower with the vaginal route, they are sustained longer and overall exposure to the drug is increased, perhaps because of the presystemic gastrointestinal or hepatic metabolism that occurs with the oral route. An additional explanation for the higher efficacy could be that there is a direct effect on the cervix that initiates the physiologic events that lead to increased uterine contractility. The sublingual route of administration has not been reported in the literatur
Sponsor: American University of Beirut Medical Center

Current Primary Outcome: -The main outcome measures will be the induction time, defined as the time from placement of the first dose of misoprostol until the time of delivery of the fetus. [ Time Frame: 48 hours ]

Original Primary Outcome: -The main outcome measures will be the induction time, defined as the time from placement of the first dose of misoprostol until the time of delivery of the fetus.

Current Secondary Outcome:

  • The entry characteristics of the patients, including age, height, weight, parity, gestational age at induction, indication for the induction, and cervical score before the start of the induction [ Time Frame: 48 hours ]
  • The delivery rate within 24 hours of prostaglandin commencement [ Time Frame: 48 hours ]
  • Number of doses of misoprostol given [ Time Frame: 48 hours ]
  • Number of unsuccessful inductions [ Time Frame: 48 hours ]
  • Length of hospital stay [ Time Frame: 48 hours ]
  • Need for surgical intervention to remove the placenta [ Time Frame: 24 hours ]


Original Secondary Outcome:

  • The entry characteristics of the patients, including age, height, weight, parity, gestational age at induction, indication for the induction, and cervical score before the start of the induction
  • The delivery rate within 24 hours of prostaglandin commencement
  • Number of doses of misoprostol given
  • Number of unsuccessful inductions
  • -Frequency of side effect including: fever (oral temp > 38° C), nausea, vomiting, diarrhea, and headache
  • Length of hospital stay
  • -Length of third stage of labor
  • Need for surgical intervention to remove the placenta


Information By: American University of Beirut Medical Center

Dates:
Date Received: September 1, 2005
Date Started: September 2004
Date Completion:
Last Updated: July 18, 2013
Last Verified: July 2013