Techniques to Improve Efficacy of Second Trimester Medical Termination

Interruption of a pregnancy after 14 weeks gestation may be required when the foetus is dead, severely malformed or in cases of maternal illness. This process is usually conducted medically in Australia, using the synthetic prostaglandin E1 analogue misoprostol. This prostaglandin, although not licensed for use in pregnancy termination, is now a common abortifacient with a large accumulated experience both within Australia and internationally. Since 1996, misoprostol has been used at King Edward Memorial Hospital as the principal agent for second trimester pregnancy termination.Misoprostol may be administered vaginally, orally, sublingually or buccally in the process of pregnancy termination. Each route of administration has its own advantages and disadvantages. The most appropriate route of administration, with the shortest duration of abortion and lowest side-effect profile has not been determined for all circumstances.The combination of mifepristone and misoprostol is an established and effective method for second trimester pregnancy termination. Prior studies have demonstrated a significant reduction in the duration of abortion with misoprostol when mifepristone priming is used. In November 2007, the TGA approved an application by the Principal Investigator of this planned study for Authorised Prescriber status for use of the antiprogesterone agent mifepristone. Since January 2008 the combination of mifepristone and misoprostol has been used at KEMH for first and second trimester pregnancy termination of pregnancy, predominantly for circumstances of severe fetal abnormality.There is however limited data on the impact of gestation on the duration of second trimester termination. Almost all published studies to date have recruited women in the early second trimester (typically with a median of 16 weeks gestation). However, most terminations of pregnancy for fetal abnormality (the most frequent reason for pregnancy interruption of a live foetus at KEMH) occur at 18-24 weeks gestation. The investigators’ experience indicates a significant impact of increasing gestation with prolongation of the duration of pregnancy termination. In this study the investigators aim to evaluate three misoprostol regimens for second trimester pregnancy termination following mifepristone priming with the primary intention to develop a protocol which results in a delivery rate within 24 hours for 95% of women at gestations <24 weeks.Secondary aims of this study will be to assess the incidence of maternal side-effects for each of the three regimens, the placental retention rates and the need for curettage for retained placental tissue. As the investigators will be using 3 different methods of misoprostol administration, the investigators will also review women’s satisfaction with the three regimens for pregnancy termination.

Official Title

Comparison of 3 Regimens Using Mifepristone and Misoprostol for Second Trimester Pregnancy Interruption

Conditions

• Pregnancy

Study Type

Interventional

Study Design

Treatment, Randomised, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Further Details

Primary outcome measures

• To compare the efficacy of the vaginal and sublingual administration of the synthetic prostaglandin misoprostol with the currently used oral administration route in second trimester pregnancy termination.
  [ Time Frame: Induction to delivery interval ] [ Designated as safety issue: No ]

Secondary outcome measures

• To compare the incidence of maternal side-effects between the three routes of prostaglandin administration.
  [ Time Frame: Admission to hospital discharge ] [ Designated as safety issue: Yes ]
• To compare the incidence of placental retention and need for curettage between the three groups
  [ Time Frame: Delivery of foetus to delivery of placenta interval ] [ Designated as safety issue: Yes ]
• To compare the impact of gestation of the duration of abortion within these three misoprostol regimens.
  [ Time Frame: Interval from commencement of prostaglandin to delivery of foetus ] [ Designated as safety issue: No ]

Study Start

April 2009- January 2011

Eligibility & Criteria

• Female aged 16-50 years

Inclusion criteria

• 4-24 weeks pregnant;
• Planned medical termination;
• Able to speak and understand English;
• No contraindication to prostaglandins.

Exclusion criteria

• Gestation < 13 weeks;
• Allergy/contraindication to misoprostol;
• Allergy/contraindication to mifepristone;
• Foetal demise.

Total Enrolment

312

Contact Details

Jan E Dickinson, MD
61 8 9340 1330
Jan.Dickinson@uwa.edu.au