Dose Comparison of Misoprostol for Cervix Ripening Before Operative Hysteroscopy.

Comparison Between 200 μg and 800 μg of Misoprostol for Cervical Ripening Prior to Operative Hysteroscopy: Randomized and Quadruple Blind Clinical Trial.

The medication misoprostol is used to facilitate the entry into the uterus of hysteroscopy surgery equipment and this research aims to compare the results of the use of this drug in two different doses trying to find the optimal one.

To perform this work we will use the misoprostol and will perform a questionnaire that will be asked during hospitalization, before, during and the 12hours after the surgery.

The patients who meet the inclusion criteria after signing the Informed Consent Form will be allocated into two groups getting misoprostol 200mcg or misoprostol 800mcg.

Study Overview

• Status: Completed
• Conditions: Cervix; Open
• Intervention / Treatment: Drug: Misoprostol 200mcg Tab; Drug: Misoprostol 800mcg Tab

Detailed Description

Background: Hysteroscopy represents a minimally invasive procedure that has been increasing its adoption in the treatment of many cervical canal and uterine cavity disorders. However, difficulties related to the introduction of the equipment through the cervix are frequent. Although several studies suggest advantages in the cervical preparation with misoprostol, reducing the resistance of the uterine cervix, systematic reviews are unison to indicate the need for clarification on the ideal dose.

Aim: Compare the intra and postoperative results of patients submitted to cervical dilatation for surgical hysteroscopy with previous use of misoprostol at doses of 200mcg or 800mcg for uterine cervix preparation at Recife school hospitals.

Methods: Randomized, quadruple-blind clinical trial with patients who underwent cervical dilatation prior to surgical hysteroscopy at Recife school hospitals, Pernambuco. Patients included will be allocated randomly into two groups. The first group will use misoprostol in the dosage of 200mcg and the second, will use the dosage of 800mcg. Administration, via the vaginal route, will occur 12 hours before performing the operative hysteroscopy. The following variables will be studied: cervical canal width, cervical length, degree of difficulty, duration and failure of cervical dilation, side effects, surgical complications and patient's satisfaction. For statistical analysis, chi-square tests of association, Fisher's exact and Mann-Whitney tests will be used to compare the groups, with an alpha error of less than 5% being considered significant.

Ethical aspects: This study will comply with Resolution 466/12 of the National Health Council and was submitted to and approved by the Professor Fernando Figueira Integral Medicine Institute Research Ethics Committee, beginning only after this approval. All participants will only be included if they voluntarily agree to participate by signing the Free and Informed Consent Form.

There are no conflicts of interest.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • PE
    • Recife, PE, Brazil, 52.050-020
      • Maria da Conceição Souto Maior

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Patients with indication for operative hysteroscopic.

Exclusion Criteria:

• Patient with contraindications to the use of prostaglandins such as asthma, glaucoma, renal failure, severe heart disease or drug allergy;
• Situations that impede the vaginal administration of medication such as major genital prolapse and virginity;
• Situations that prevent hysteroscopy as major uterine bleeding, diagnosis or suspected topical pregnancy and genital infection such as vaginosis and cervicitis;
• Situations that may influence cervical canal width such as a history of isthmo-cervical incompetence or major cervical surgery like conization or trachelotomy; presence of any structure like uterine fibroid or endometrial polyp inside the cervical canal or though the cervical os; patients on systemic or vaginal estrogen replacement therapy or who have recently used gonadotropin hormone-releasing hormone analogues.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Misoprostol 200mcg; In this group, the participants will receive 200mcg of misoprostol, single dose, via the vaginal route.	Drug: Misoprostol 200mcg Tab; In the misoprostol 200mcg group there will be one tablet of 200mcg and three identical tablets in shape, size and color without pharmacological properties. These four tablets will be single dose administered via vaginal route for each participant.; Other Names: synthetic prostaglandin
Active Comparator: Misoprostol 800mcg; In this group, the participants will receive 800mcg of misoprostol, single dose, via the vaginal route.	Drug: Misoprostol 800mcg Tab; In the misoprostol 800mcg group there will be four tablets of 200mcg. These four tablets will be single dose administered via vaginal route for each participant.; Other Names: synthetic prostaglandin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cervical canal width.	Maximum size of dilator that passes through the internal os without resistance.	during the surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time required to dilate the cervix to 9mm.	Time necessary to achieve cervical permeability up to 9mm by introducting the Hegar dilators through the internal os.	during the surgery
Ease of cervical dilation.	The feeling of ease or difficulty reported by the surgeon while dilating the cervix. Evaluated by LIKERT scale. It varies from one to five, one meaning very difficult and five meaning very easy .	during the surgery
Length of the cervix.	The distance between the external and the internal os measured in centimeters.	during the surgery
Abandonment of the procedure due to cervical dilation failure.	Impossibility of perform operative hysteroscopy due to difficulty to achieve complete cervical dilation up to 9mm.	during the surgery
Intraoperative complications.	Complications related to the difficulty of the dilate de cervical canal like uterine perforation, creation of false path, cervical tears and post-dilation bleeding.	during the surgery
Side effects due to the use of the misoprostol.	Adverse effects as nausea, vomiting, diarrhea, fever, chills, abdominal pain or any other complaint resulting from the use of the medication.	24 hours
Pain intensity	The highest level of pain reported by the patient according the Visual Analog Scale evaluated at 3 moments: at the time of hospitalization, at the preoperative time (between medication administration and anesthesia onset) and at the postoperative time (12 hours after the procedure).	24 hours
Patient satisfaction degree.	The satisfaction with the medication, reported by the participant. Evaluated by LIKERT scale. It varies from one to five, one meaning less than satisfied and five meaning very satisfied with the drug.	24 hours

Collaborators and Investigators

• Sponsor: Professor Fernando Figueira Integral Medicine Institute
• Investigators: Study Director: Aurélio Costa, PhD, Instituto Materno Infantil Prof. Fernando Figueira

Publications and helpful links

General Publications

• Maior MDCFS, Souza ASR, Souza GFA, da Costa AAR. Comparison between 200 μg and 800 μg of vaginal misoprostol for cervical ripening before operative hysteroscopy: A randomized controlled trial. Int J Gynaecol Obstet. 2022 Jul;158(1):205-212. doi: 10.1002/ijgo.13984. Epub 2021 Nov 3.

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2019
• Primary Completion (Actual): September 11, 2020
• Study Completion (Actual): September 12, 2020

Study Registration Dates

• First Submitted: November 2, 2019
• First Submitted That Met QC Criteria: November 4, 2019
• First Posted (Actual): November 5, 2019

Study Record Updates

• Last Update Posted (Actual): October 8, 2020
• Last Update Submitted That Met QC Criteria: October 6, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Misoprostol; Operative Hysteroscopy
• Additional Relevant MeSH Terms: Uterine Cervical Diseases; Uterine Diseases; Pregnancy Complications; Abortion, Habitual; Abortion, Spontaneous; Uterine Cervical Incompetence; Physiological Effects of Drugs; Gastrointestinal Agents; Reproductive Control Agents; Anti-Ulcer Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Oxytocics; Misoprostol
• Other Study ID Numbers: MISO.

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No