Introduction

This is the first prospective study that uses the same misoprostol regimen in pregnancies of 64-140 days gestation until abortion and comparing the 24^th and 48^th intervals between mifepristone and misoprostol administration throughout these gestational weeks. The present project forms part of the strategy of the Concept Foundation to undertake clinical research to obtain prospective data for registration of medical abortion regimen beyond 63 days of gestation. Registration would give justification for its use and avoid off-label use of these drugs at the proposed gestations. If the 24^th regimen is proven to be non-inferior to the 48^th regimen then it could be recommended in settings where it is more convenient for women to return for misoprostol administration one day rather than two days after mifepristone. The trial will require 12 to 14 months for data collection at each centre and between 6 and 12 months of centralized data analysis in Thailand.

Aims and Objectives

The aim of this study is to collect data on efficacy, side effects and complications while using this regimen to induce abortion. Also to investigate whether both 24^th and 48^th intervals between mifepristone and misoprostol give similar expulsion rates.

Methodology

The proposed study is a prospective, randomized multicentre trial that will involve up to 670 pregnant women with 64-140 days of gestational age (i.e. 10^th – 20^th weeks) requesting legal termination of pregnancy at clinics providing abortion services in India. Sweden, Thailand and Vietnam; 75 in Chandigarh, 75 in Delhi, 200 in Hanoi, 200 in Bangkok and Khon Kean (for 64-104 days LMP only) and 120 in Stockholm. Eligible women who wish to join the study will first receive 200 mg mifepristone, followed either 24^th or 48^th later by 0.8 mg misoprostol, administered vaginally. The treatment will continue with 0.4 mg misoprostol administered sublingually 3 hourly until abortion or up to a total of 4 doses of 0.4 mg misoprostol, whichever comes first. If the woman has not aborted during the three hours following the last dose of 0.4 mg misoprostol, she will be given 200 mg mifepristone and allowed to rest until the next morning when the same misoprostol regimen (0.8 mg followed by 0.4 mg doses) will continue. The final outcome regarding the efficacy, side-effects since treatment and acceptability will be assessed at the follow up visits on Day 14-15 of the study.

Data Analysis

A computer generated randomization sequence will be produced centrally in chulalongkorn University, Bangkok to assign participants within each centre to receive misoprostol 24 hr or 48 hrs after mifepristone. The randomization will use randomly permuted blocks and the sequence will be kept concealed from the staff at Concept Foundation and the trial investigators. Participating centres will record the data on paper data collection forms, enter them and send them electronically on a weekly basis using a Web-based system developed by a statistical consultant to Concept Foundation. Recruitment and data quality will be monitored by the staff of the Concept Foundation and the statistical consultant using this system.

Justification of Project

Abortion can be induced safely and effectively by using combination of mifepristone and misoprostol. These regimens for induction of abortion have not been extensively compared in a clinical trial. This study will help to provide answers as to which regimen is optimal from a clinical perspective. The present project forms part of the strategy of the Concept Foundation to undertake clinical research to obtain prospective data for registration of medical abortion regimen beyond 63 days of gestation. Registration would give justification for its use and avoid off-label use of these drugs at the proposed gestations.