Misoprostol 400 µg Versus 200 µg for Cervical Ripening in 1st Trimester Miscarriage (MISO200)

Comparison Between 400 µg or 200 µg of Misoprostol for Cervical Dilatation in 1st Trimester Miscarriage - A Clinical Trial

Local current protocol for cervical ripening in 1st trimester miscarriage recommends 400 µg of misoprostol intravaginally 3 hours before uterine evacuation. This regime has been recommended by some international guidelines . So far, there are no recent studies comparing cervical dilatation between 400 µg of misoprostol and a reduced dose (e.g., 200 µg) for 6 hours. If cervical ripening is similar between these two regimens(i.e., 200µg regimen is not inferior to 400µg regimen), costs reductions and lower side effects may be issued without losing quality of cervix dilatation.

Study Overview

• Status: Completed
• Conditions: Miscarriage in First Trimester
• Intervention / Treatment: Drug: Misoprostol 400mcg Tab; Drug: Misoprostol 200mcg Tab

Detailed Description

Miscarriage is defined by the World Health Organization as the interruption of the pregnancy up to 20-23 weeks, or the products of pregnancy weighing less than 500 grams (1). Nearly 15% of known pregnancies end in miscarriage, especially in the first 12 weeks. Estimates indicate that 68000 women die worldwide each year, as a result of unsafe abortions. Abortions are the major cause of maternal death, particularly in Latin America and the Caribbean. In cases of retained and incomplete abortions, uterine emptying is recommended. In the first trimester of pregnancy, either pharmacological or surgical procedure is accepted according to international guidelines.

Pharmacological treatment for uterine evacuation includes the administration of mifepristone and misoprostol or misoprostol alone. Nevertheless, surgical methods have been shown a greater acceptability and patient satisfaction due to a reduced incidence of adverse effects. Currently, Manual Vacuum Aspiration (MVA) is the technique recommended by the Brazilian Ministry of Health and the Brazilian Federation of Gynecology and Obstetrics.

MVA should be performed after cervical ripening. This pre-surgical procedure makes the procedure safer and more effective. In Brazil, misoprostol is the most suitable drug to be used in these cases because of its efficacy, ease of use, low cost, stability at room temperature, and availability. Misoprostol is a synthetic prostaglandin E1 analog and can be administered by oral, sublingual, buccal, rectal, and vaginal routes.

• Study Type: Interventional
• Enrollment (Actual): 211
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • RS
    • Porto Alegre, RS, Brazil, 90035-903
      • HCPA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• All patients admitted at the Gynecological emergency Unit at Hospital de Clínicas de Porto Alegre scheduled for uterine evacuation with <12 weeks of gestation.

Exclusion Criteria:

• patients who do not wish to participate in the project;
• patients with ectopic pregnancy;
• patients with comorbidities (heart failure congestive, chronic obstructive pulmonary disease);
• patients with hypovolemic shock;
• patients with cervical incompetence;
• patients with infected miscarriage/abortion (presence of fever, pus from the cervix, leukocytosis [> 14000]);
• patients with twin pregnancy;
• patients with Marfan syndrome;
• patients allergic to misoprostol;
• patients with coagulopathy;
• patients with opening of cervical internal os (4 mm of dilatation at the time of consultation);
• patients with previous surgery of the cervix (conization);
• patients with concomitant use of IUDs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Misoprostol 400 µg; Participants received misoprostol 400 µg: 2 tablets of misoprostol (200µg each) introduced into the vagina, at least 6 hours before the Manual Vacuum Aspiration (MVA) procedure.	Drug: Misoprostol 400mcg Tab; 400µg of misoprostol (2 tablets); Other Names: Misoprostol control
Experimental: Misoprostol 200 µg; Participants received misoprostol 200 µg: 1 tablet of misoprostol introduced into the vagina, at least 6 hours before the Manual Vacuum Aspiration procedure.	Drug: Misoprostol 200mcg Tab; 200µg of misoprostol (1 tablet); Other Names: Misoprostol comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Required Cervix Dilation at Initiation of the Manual Vacuum Aspiration	this outcome identifies patients that had to have a mechanical dilator for opening the cervix to perform appropriate Manual Vacuum Aspiration	baseline at initiation of the Manual Vacuum Aspiration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With a Presence of a Uterine Cervical Canal With ≥8 mm of Dilation	This outcome measures how many mm of dilation the cervical canal has before the procedure. Cervical permeability (≥8 mm of dilation, used as a cut-off) was measured using Karman cannulas, from higher to low diameter.	Baseline before Manual Vacuum Aspiration procedure

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Score (VAS)	Pain scores were assessed using a verbal analog scale (VAS), ranging from zero (no pain) to 10 (worst possible pain)	before Manual Vacuum Aspiration

Collaborators and Investigators

• Sponsor: Hospital de Clinicas de Porto Alegre
• Investigators: Principal Investigator: Ricardo F Ricardo, MD, PhD, HCPA

Publications and helpful links

General Publications

• Kapp N, Lohr PA, Ngo TD, Hayes JL. Cervical preparation for first trimester surgical abortion. Cochrane Database Syst Rev. 2010 Feb 17;(2):CD007207. doi: 10.1002/14651858.CD007207.pub2.
• Blanchard K, Clark S, Winikoff B, Gaines G, Kabani G, Shannon C. Misoprostol for women's health: a review. Obstet Gynecol. 2002 Feb;99(2):316-32. doi: 10.1016/s0029-7844(01)01701-x.
• Marret H, Simon E, Beucher G, Dreyfus M, Gaudineau A, Vayssiere C, Lesavre M, Pluchon M, Winer N, Fernandez H, Aubert J, Bejan-Angoulvant T, Jonville-Bera AP, Clouqueur E, Houfflin-Debarge V, Garrigue A, Pierre F; College national des gynecologues obstetriciens francais. Overview and expert assessment of off-label use of misoprostol in obstetrics and gynaecology: review and report by the College national des gynecologues obstetriciens francais. Eur J Obstet Gynecol Reprod Biol. 2015 Apr;187:80-4. doi: 10.1016/j.ejogrb.2015.01.018. Epub 2015 Jan 31.
• National Collaborating Centre for Women's and Children's Health (UK). Ectopic Pregnancy and Miscarriage: Diagnosis and Initial Management in Early Pregnancy of Ectopic Pregnancy and Miscarriage. London: RCOG Press; 2012 Dec. Available from http://www.ncbi.nlm.nih.gov/books/NBK132775/
• ACOG Committee Opinion. American College of Obstetrician and Gynecologist. ACOG Committee Opinion. Number 283, May 2003. New U.S. Food and Drug Administration labeling on Cytotec (misoprostol) use and pregnancy. Obstet Gynecol. 2003 May;101(5 Pt 1):1049-50. doi: 10.1016/s0029-7844(03)00396-x.
• Tang J, Kapp N, Dragoman M, de Souza JP. WHO recommendations for misoprostol use for obstetric and gynecologic indications. Int J Gynaecol Obstet. 2013 May;121(2):186-9. doi: 10.1016/j.ijgo.2012.12.009. Epub 2013 Feb 19.

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2016
• Primary Completion (Actual): October 19, 2019
• Study Completion (Actual): June 30, 2020

Study Registration Dates

• First Submitted: November 4, 2016
• First Submitted That Met QC Criteria: November 4, 2016
• First Posted (Estimate): November 6, 2016

Study Record Updates

• Last Update Posted (Actual): April 30, 2021
• Last Update Submitted That Met QC Criteria: April 29, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: misoprostol; miscarriage
• Additional Relevant MeSH Terms: Pregnancy Complications; Abortion, Spontaneous; Physiological Effects of Drugs; Gastrointestinal Agents; Reproductive Control Agents; Anti-Ulcer Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Oxytocics; Misoprostol
• Other Study ID Numbers: 160309

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: We intend to share raw data with other researchers
• IPD Sharing Time Frame: unlimited
• IPD Sharing Access Criteria: free to read
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)