title: 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: BACKGROUND
  Pain 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
  We 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.
  
  
  CONCLUSIONS
  Although 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.
  
  
  BACKGROUND
  ACTRN12613000017729 (Prospectively registered 8/1/2013).
authors.affiliation: Department of Reproductive Health and Research, WHO, UNFP/UNDP/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Geneva, Switzerland. mvd2116@gmail.com.
authors.forename: Monica V
authors.initials: MV
authors.lastname: Dragoman
authors.affiliation: Advancing New Standards in Reproductive Health (ANSIRH), Bixby Center for Global Reproductive Health, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, USA.|Ibis Reproductive Health, Oakland, CA, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Grossman
authors.affiliation: Department of Reproductive Health and Research, WHO, UNFP/UNDP/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Geneva, Switzerland.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Kapp
authors.affiliation: Department of Reproductive Health and Research, WHO, UNFP/UNDP/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Geneva, Switzerland.
authors.forename: Nguyen My
authors.initials: NM
authors.lastname: Huong
authors.affiliation: Department of Reproductive Health and Research, WHO, UNFP/UNDP/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Geneva, Switzerland.
authors.forename: Ndema
authors.initials: N
authors.lastname: Habib
authors.affiliation: National Hospital for Obstetrics and Gynecology, Hanoi, Viet Nam.
authors.forename: Duong Lan
authors.initials: DL
authors.lastname: Dung
authors.affiliation: Center for Environment Health and Population Activities, Kathmandu, Nepal.
authors.forename: Anand
authors.initials: A
authors.lastname: Tamang
mesh_terms: D000020:Abortifacient Agents, Nonsteroidal / Q000009:adverse effects; D000021:Abortifacient Agents, Steroidal / Q000009:adverse effects; D000028:Abortion, Induced / Q000009:adverse effects* / Q000379:methods; D000293:Adolescent; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000627:therapeutic use; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use; D000932:Antiemetics / Q000008:administration & dosage / Q000627:therapeutic use; D002985:Clinical Protocols; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000627:therapeutic use; D008787:Metoclopramide / Q000008:administration & dosage; D015735:Mifepristone / Q000009:adverse effects*; D016595:Misoprostol / Q000009:adverse effects*; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control*; D059408:Pain Management / Q000379:methods*; D020250:Postoperative Nausea and Vomiting / Q000517:prevention & control; D011247:Pregnancy; D012107:Research Design; D014147:Tramadol / Q000008:administration & dosage / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000020:Abortifacient Agents, Nonsteroidal; D000021:Abortifacient Agents, Steroidal; D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D000932:Antiemetics; D016595:Misoprostol; D015735:Mifepristone; D014147:Tramadol; D008787:Metoclopramide; D007052:Ibuprofen
keywords: Medical abortion; Mifepristone; Misoprostol; Pain management