Techniques to Improve Efficacy of Second Trimester Medical Termination

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Jan Dickinson, King Edward Memorial Hospital
ClinicalTrials.gov Identifier:
NCT00864799
First received: March 18, 2009
Last updated: July 23, 2013
Last verified: July 2013
  Purpose

Interruption of a pregnancy after 14 weeks gestation may be required when the fetus 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 (Therapeutic Goods Administration) 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 fetus 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.


Condition Intervention
Pregnancy
Drug: Misoprostol

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Comparison of 3 Regimens Using Mifepristone and Misoprostol for Second Trimester Pregnancy Interruption.

Resource links provided by NLM:


Further study details as provided by King Edward Memorial Hospital:

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 fetus 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 fetus ] [ Designated as safety issue: No ]

Enrollment: 302
Study Start Date: April 2009
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Vaginal misoprostol

Women allocated to the vaginal misoprostol management protocol will receive a loading dose of 800 mcg misoprostol vaginally followed in 4 hours by 400 mcg vaginal misoprostol, the latter repeated every 4 hours for a maximum of 4 doses.

If abortion does not occur within 24 hours of commencement of this regimen, the sequence will be repeated.

If delivery is not accomplished within 48 hours of prostaglandin commencement, a transcervical Foley catheter will be inserted and a solution of prostaglandin F2 alpha infused 2-hourly until delivery occurs.

Drug: Misoprostol
Comparison of 3 routes of administration of misoprostol for termination of pregnancy 14-24 weeks
Active Comparator: Oral misoprostol

Women allocated to the standard management protocol will receive a loading dose of 800 mcg misoprostol vaginally followed in 3 hours by 400 mcg misoprostol orally, the latter repeated every 3-hours to a maximum of 4 oral doses.

If abortion does not occur within 24 hours of commencement of this regimen, the sequence will be repeated.

If delivery is not accomplished within 48 hours of prostaglandin commencement, a transcervical Foley catheter will be inserted and a solution of prostaglandin F2 alpha infused 2-hourly until delivery occurs.

Drug: Misoprostol
Comparison of 3 routes of administration of misoprostol for termination of pregnancy 14-24 weeks
Active Comparator: Sublingual misoprostol

Women allocated to the sublingual misoprostol protocol will receive a loading dose of 800 mcg misoprostol vaginally followed in 3 hours by 400 mcg sublingual misoprostol, the latter repeated every 3 hours for a maximum of 4 doses.

If abortion does not occur within 24 hours of commencement of this regimen, the sequence will be repeated.

If delivery is not accomplished within 48 hours of prostaglandin commencement, a transcervical Foley catheter will be inserted and a solution of prostaglandin F2 alpha infused 2-hourly until delivery occurs.

Drug: Misoprostol
Comparison of 3 routes of administration of misoprostol for termination of pregnancy 14-24 weeks

Detailed Description:

Aims:

  1. To compare the efficacy of the vaginal and sublingual administration of the synthetic prostaglandin misoprostol with the currently used vaginal administration route in second trimester pregnancy termination.
  2. To compare the impact of gestation of the duration of abortion within these three misoprostol regimens.
  3. To compare the incidence of maternal side-effects between the three routes of prostaglandin administration.
  4. To compare the incidence of placental retention and need for curettage between the three groups
  Eligibility

Ages Eligible for Study:   16 Years to 50 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 14-24 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
  • fetal demise
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00864799

Locations
Australia, Western Australia
King Edward Memorial Hospital
Perth, Western Australia, Australia, 6008
Sponsors and Collaborators
King Edward Memorial Hospital
Investigators
Principal Investigator: Jan E Dickinson, MD The University of Western Australia
  More Information

No publications provided by King Edward Memorial Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Jan Dickinson, Professor Maternal Fetal Medicine, King Edward Memorial Hospital
ClinicalTrials.gov Identifier: NCT00864799     History of Changes
Other Study ID Numbers: 1624/EW
Study First Received: March 18, 2009
Last Updated: July 23, 2013
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by King Edward Memorial Hospital:
Abortion
Misoprostol
Mifepristone
Pregnancy
Fetus

Additional relevant MeSH terms:
Mifepristone
Misoprostol
Abortifacient Agents, Steroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Contraceptives, Oral, Synthetic
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Contraceptives, Postcoital, Synthetic
Contraceptives, Postcoital
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Luteolytic Agents
Menstruation-Inducing Agents
Abortifacient Agents, Nonsteroidal
Anti-Ulcer Agents
Gastrointestinal Agents
Oxytocics

ClinicalTrials.gov processed this record on August 28, 2014