Clinical trial NCT02957305: Misoprostol 400 µg Versus 200 µg for Cervical Ripening in 1st Trimester Miscarriage
Official title: Comparison Between 400 µg or 200 µg of Misoprostol for Cervical Dilatation in 1st Trimester Miscarriage - A Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Miscarriage in First Trimester
Keywords: misoprostol
miscarriage
Lead sponsor: Hospital de Clinicas de Porto Alegre
Sponsor class: OTHER
First posted: 2016-11-06
Enrollment: 211
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants Who Required Cervix Dilation at Initiation of the Manual Vacuum Aspiration
timeFrame: baseline at initiation of the Manual Vacuum Aspiration
Secondary outcomes:
measure: Number of Participants With a Presence of a Uterine Cervical Canal With ≥8 mm of Dilation
timeFrame: Baseline before Manual Vacuum Aspiration procedure
Other outcomes:
measure: Pain Score (VAS)
timeFrame: before Manual Vacuum Aspiration
Locations:
city: Porto Alegre
country: Brazil
facility: HCPA
state: RS
Study officials:
affiliation: HCPA
name: Ricardo F Ricardo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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/
citation: 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.
citation: 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.