Second Trimester Medical Abortion (RAPM)

• ClinicalTrials.gov Identifier: NCT04160221
• Recruitment Status: Recruiting
• First Posted: November 12, 2019
• Last Update Posted: November 5, 2021
• Sponsor: Sheba Medical Center
• Collaborator: Stanford University
• Information provided by (Responsible Party): Dr. Aya Mohr-Sasson, Sheba Medical Center

Tracking Information

• First Submitted Date: November 6, 2019
• First Posted Date: November 12, 2019
• Last Update Posted Date: November 5, 2021
• Actual Study Start Date: November 1, 2019
• Estimated Primary Completion Date: October 1, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 8, 2019)

Induction-abortion time [ Time Frame: Through completion of abortion, an estimated period of up to 3 days ]

Total induction to complete abortion ( estimated by hours)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 8, 2019)

• Fever [ Time Frame: From the beginning until completion of abortion,estimated up to two weeks ]
  Fever measure above 38 degrees
• Excessive blood loss [ Time Frame: From the beginning until completion of abortion, estimated up to two weeks ]
  Excessive blood loss estimated by the medical team ( remnants of blood on pad, active bleeding estimated to be equal to menstruation, heavier bleeding including blood clots, blood loss leading to hemodynamically instability including tachycardia and/or reduced blood pressure)
• Any emergency department visit [ Time Frame: From the beginning until completion of abortion, estimated up to two weeks ]
  Emergency department visit during the abortion or reported on follow up

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Second Trimester Medical Abortion
• Official Title: Second Trimester Medical Abortion- New Strategies
• Brief Summary: The use of Mifepristone, an antiprogesterone, and Misoprostol together, has been shown to make the medial abortion process more efficient and reduce the induction-to-abortion interval by almost 50%. Despite the recommended 24-48 Mifepristone-Misoprostol interval, recent retrospective study of a flexible interval, have revealed shorter total abortion time with shorter intervals. In this study we aim to compare 24 to 12 hours Mifepristone to Misoprostol intervals

Detailed Description

Women are looking for termination of pregnancies in the second trimester, after 12 weeks of gestation for social and medical reasons, as well as due to intrauterine fetal demise. Both surgical and medical methods can be used, depending on the patients' preference, providers skills, availability of drugs and instruments and more. Methods of medical abortion can be performed with the use of prostaglandin analogues, mifepristone, oxytocin, foley catheter and osmotic dilators. Misoprostol, a prostaglandin analogue (PGE1), is currently recommended over other agents due to its efficacy, low cost and ease of use. Misoprostol can be used alone or in combination with other agents. The use of Mifepristone, an antiprogesterone, and Misoprostol together, has been shown to make the medial abortion process more efficient and reduce the induction-to-abortion interval by almost 50%. Current guidelines recommend the use of Mifepristone 200 mg orally, followed by Misoprostol 400 mcg every 3-4, hours 24-48 later until expulsion of the fetus. Despite the recommended 24-48 Mifepristone-Misoprostol interval, recent retrospective study of a flexible interval, ≤12, 12-24 and >24 hours, have revealed shorter total abortion time (time from Mifepristone to fetal expulsion) with the shorter intervals. Thus, strict adherence to current guidelines may unnecessarily prolong the abortion procedure.

Objective Prompted by the need to explore more beneficial methods and regimes for second trimester medical abortion, we aim to compare 24 to 12 hours Mifepristone to Misoprostol intervals

Material and Methods Women eligible for second trimester medical abortion will be approached to enroll in the study at the clinic or emergency room when they arrive to schedule medical abortion. A research staff member will obtain informed consent. The patient will undergo a blood test including blood type, complete blood count and chemistry. Basic demographic information will be collected. A complete history and physical assessment will be performed. If an ultrasound report is not available to confirm gestational age dating, ultrasound will be performed to determine gestational age. A baseline cervical exam will be done at this visit to assess cervical consistency. Patients will be randomized into one of two groups according to a computer-generated random allocation sequence. Sequentially numbered sealed opaque envelopes will be used to provide allocation.

• Patients allocated to group 1 will receive 200 mg Mifepristone orally, followed by Misoprostol 400 mcg vaginally 12 hours later and subsequently 400 mcg orally every three hours until fetal expulsion to a maximum of 5 doses.
• Patients allocated to group 2 will receive 200 mg Mifepristone orally, followed by Misoprostol 400 mcg vaginally 24 hours later and subsequently 400 mcg orally every three hours until fetal expulsion to a maximum of 5 doses.

Patients will be discharged home after receiving Mifepristone, and hospitalized upon arrival for the Misoprostol administration.

If the abortion is not complete after five doses, the woman may be allowed to rest for 12 hours before starting the cycle again.

All participants will be contacted by phone as well as a chart review conducted to assess for delayed complications. During this follow up time, they will be asked to notify the research team if they should develop fatigue, malaise, abdominal pain, or jaundice. If these symptoms occur, a workup for liver injury would be performed. Patients will be asked to obtain repeat liver function tests within two weeks post-procedure to compare to their baseline hepatic panel.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Medical Abortion, Complete or Unspecified, Without Complication

Intervention

• Other: 12 hours interval
  Time interval between treatments
• Other: 24 hours interval
  Time interval between treatments

Study Arms

• Active Comparator: 12 hours interval
  Mifepristone followed by Misoprostol treatment
  Intervention: Other: 12 hours interval
• Active Comparator: 24 hours interval
  Mifepristone followed by Misoprostol treatment
  Intervention: Other: 24 hours interval

Publications *

• Lohr PA, Hayes JL, Gemzell-Danielsson K. Surgical versus medical methods for second trimester induced abortion. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD006714. doi: 10.1002/14651858.CD006714.pub2.
• ACOG Practice Bulletin No. 135: Second-trimester abortion. Obstet Gynecol. 2013 Jun;121(6):1394-1406. doi: 10.1097/01.AOG.0000431056.79334.cc. No abstract available.
• Borgatta L, Kapp N; Society of Family Planning. Clinical guidelines. Labor induction abortion in the second trimester. Contraception. 2011 Jul;84(1):4-18. doi: 10.1016/j.contraception.2011.02.005. Epub 2011 Mar 30.
• Costescu D, Guilbert E. No. 360-Induced Abortion: Surgical Abortion and Second Trimester Medical Methods. J Obstet Gynaecol Can. 2018 Jun;40(6):750-783. doi: 10.1016/j.jogc.2017.12.010.
• Li HWR, Gemzell-Danielsson K. Mechanisms of action of emergency contraception pills. Eur J Contracept Reprod Health Care. 2019 Feb;24(1):11-12. doi: 10.1080/13625187.2018.1555663. Epub 2019 Jan 21. No abstract available.
• Donnez J, Tomaszewski J, Vazquez F, Bouchard P, Lemieszczuk B, Baro F, Nouri K, Selvaggi L, Sodowski K, Bestel E, Terrill P, Osterloh I, Loumaye E; PEARL II Study Group. Ulipristal acetate versus leuprolide acetate for uterine fibroids. N Engl J Med. 2012 Feb 2;366(5):421-32. doi: 10.1056/NEJMoa1103180.
• Blithe DL, Nieman LK, Blye RP, Stratton P, Passaro M. Development of the selective progesterone receptor modulator CDB-2914 for clinical indications. Steroids. 2003 Nov;68(10-13):1013-7. doi: 10.1016/s0039-128x(03)00118-1.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 8, 2019): 300
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 1, 2022
• Estimated Primary Completion Date: October 1, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Women aged 18 years and older about to undergo medical second trimester abortion
• 12+0 to 28+0 weeks of gestation
• Singleton intrauterine pregnancy
• Able to sign informed consent

Exclusion Criteria:

• Inability to give informed consent
• Allergy to any of the drugs used in the study
• Genital bleeding of unknown etiology; cancer of the breast, cervix, uterus, or ovaries; hepatic disease (current or history of)
• Multiple gestation
• Rupture of membranes
• Taken a CYP3A4 inhibitor within 5 elimination half-lives of the drug from the procedure
• Pre-dosing abnormal liver function tests

• Patients at increased risk of hepatitis based on a history of any of the following:

  • Any history of underlying liver disorder, including hepatitis
  • A family history of hepatitis or currently living with a person 441 who has been given a diagnosis of hepatitis
  • A history of or currently working as a sex worker
  • A history of or currently using IV drugs
  • A self-reported history of alcoholic dependency or abuse

Sex/Gender

• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Female

• Ages: 18 Years to 43 Years (Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Aya A Mohr-Sasson, M.D; 97235302777 ext 97235302777; mohraya@gmail.com

Contact: Dr. A Mohr-Sasson, M.D; 97235302777 ext 97235302777; mohraya@gmail.com

• Listed Location Countries: Israel

Administrative Information

• NCT Number: NCT04160221
• Other Study ID Numbers: 6416-19
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Dr. Aya Mohr-Sasson, Sheba Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Sheba Medical Center
• Original Study Sponsor: Same as current
• Collaborators: Stanford University

Investigators

• Principal Investigator: Aya A Mohr-Sasson, M.D; Sheba Medical Center

• PRS Account: Sheba Medical Center
• Verification Date: October 2021