Two prophylactic medication approaches in addition to a pain control regimen for early medical abortion < 63 days’ gestation with mifepristone and misoprostol: study protocol for a randomized, controlled trial

Abstract

BackgroundPain is often cited as one of the worst features of medical abortion. Further, inadequate pain management may motivate some women to seek unnecessary clinical care. There is a need to identify effective methods for pain control in this setting.Methods/DesignWe propose a randomized, placebo-controlled trial. 576 participants (288 nulliparous; 288 parous) from study sites in Nepal, South Africa and Vietnam will be randomly allocated to one of three treatments: (1) ibuprofen 400 mg PO and metoclopramide 10 mg PO; (2) tramadol 50 mg PO and a placebo; or (3) two placebo pills, to be taken immediately before misoprostol and repeated once four hours later. All women will be provided with supplementary analgesia for use as needed during the medical abortion. We hypothesize that women receiving prophylactic analgesia will report lower maximal pain scores in the first 8 h following misoprostol administration compared to women receiving placebos for medical abortion through 63 days’ gestation. Our primary objective is to determine whether prophylactic administration of ibuprofen and metoclopramide or tramadol provides superior pain relief compared to analgesia administration after pain begins, measured during the first eight hours after misoprostol administration. Secondary objectives include identifying covariates associated with higher reported pain scores; determining any impact of the study medicines on medical abortion success; and, qualitatively exploring women’s physical experiences of medical abortion, especially related to pain, and how can they be improved. Data sources include medical records, participant symptom diaries and interview data obtained on the day of enrollment, during the medical abortion, and at follow-up. Participants will be contacted via telephone on day 3 and return for follow-up will occur approximately 14 days after mifepristone, concluding study participation. A subset of 42 women will also be invited to undergo in-depth qualitative interviews following study completion.DiscussionAlthough pain is one of the most common side effects encountered with medical abortion, little is known about optimal pain management for this process. This multi-arm trial design offers an efficient approach to evaluating two prophylactic pain management regimens compared to use of pain medication as needed.Trial registration ACTRN12613000017729 (Prospectively registered 8/1/2013).

Experiences with pain of early medical abortion: qualitative results from Nepal, South Africa, and Vietnam

“…The trial was conducted in Kathmandu, Nepal; Rustenburg, South Africa; and Hanoi, Vietnam. Participants were randomized in a 1:1:1 allocation ratio to either one of two active prophylactic pain management arms (group 1: tramadol 50 mg and a placebo, or group 2: ibuprofen 400 mg and metoclopramide 10 mg) or a placebo arm (group 3) [19]. Study treatment was given at the time of misoprostol administration and repeated 4 h later.…”

“…Written informed consent was obtained from all participants before conducting the interviews. The full study protocol has been previously published [19].…”

Two prophylactic pain management regimens for medical abortion ≤63 days' gestation with mifepristone and misoprostol: A multicenter, randomized, placebo-controlled trial

“…Secondary outcomes included use of additional analgesia, side effects, and satisfaction. The full study protocol has been published [7] .…”

“…The WHO Ethics Review Committee (Geneva, Switzerland), Nepal Health Research Council (Kathmandu, Nepal), Ministry of Health in Vietnam (Hanoi, Vietnam), Human Research Ethics Committee of the University of Witwatersrand (Johannesburg, South Africa), and Allendale Investigational Review Board (USA) approved the trial. We previously published the study protocol [7] .…”

“…WHO also identified that research to inform more pain management options for medical abortion, including additional medicines and evaluation of the timing of pain medication administration, is a priority [1] . We aimed to evaluate whether prophylactic administration of tramadol or ibuprofen plus metoclopramide are superior to placebo combined with analgesia administration after pain begins during the medical abortion process [7] .…”