Nonsurgical Management of Cesarean Scar Niche Related Abnormal Uterine Bleeding

Sponsor

Saudi German Hospital - Madinah (Other)

Overall Status

Completed

CT.gov ID

NCT05594186

Collaborator

(none)

158

Enrollment

Location

Arms

43.7

Actual Duration (Months)

3.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A study of the effect of three different nonsurgical methods for management of abnormal uterine bleeding caused by cesarean scar niche. The study was conducted at the Obstetrics and Gynaecology department of the Saudi German Hospital in Madinah- Saudi Arabia, during the period between March 2019 to October 2022. The study protocol was in accordance with the Helsinki declaration 1964 and the later amendments. A prospective approval was granted by the human research ethics committee of the hospital and the study participants have signed an informed consent.

Condition or Disease	Intervention/Treatment	Phase
Intermenstrual Bleeding	Drug: Tranexamic acid, Oral contraceptive pills and the Levonorgestrel-releasing intrauterine system.	N/A

Detailed Description

The study included 158 patients aged between 20 and 40 years who had a history of at least one caesarean delivery and presented with abnormal uterine bleeding in the form of postmenstrual spotting defined as bloody or brownish discharge of more than two days after the end of menstruation, with the total duration of (menses and spotting) of more than 7 days, or intermenstrual bleeding that starts after the end of the menses, who were diagnosed to have a caesarean scar niche by saline infusion sonography. Cesarean scar niche was defined as an anechoic triangular indentation at the site of the previous cesarean scar with a depth of at least 2 mm. Exclusion criteria were: pregnancy, desire for fertility within one year of enrolment in the study, any medical condition contraindicating the use of combined oral contraceptive pills, history of abnormal uterine bleeding dating before the last caesarean section, use of any hormonal treatment 3 months prior to enrolment, coagulopathy, and organic causes of bleeding like uterine fibroids, adenomyosis or endometrial hyperplasia. Saline infusion sonography was done, in which instillation of saline solution into the uterine cavity, enhanced the transvaginal ultrasonographic image by providing a sonolucent contrast medium to allow for better visualization and delineation of the defect. Evaluation was performed according to the 2019 modified Delphi procedure where the basic evaluation of CS niche included measurements of the length, depth and width of the defect, the residual myometrial thickness (RMT) and the adjacent myometrial thickness (AMT). All measurements were made in the sagittal plane except the width which was measured in the transverse plane. The 4.5 MHz endovaginal transducer (Canon Xario 200G Ultrasound, Japan) was used.

Using an Open Epi version 3.21 computer-based software, patients were divided into four groups (A, B, C and D). Patients in group A, received Tranexamic acid 1300 mg (2 tablets of 650 mg) three times daily for 5 days starting from the first day of menses for 12 months. Patients in group B, received combined oral contraceptive pill (OCP) once daily for 21 days starting from the first day of menses, then to have a one-week pill free period to allow for a withdrawal bleed, and that was repeated for 12 cycles. Patients in group C, received a combination of Tranexamic acid 1300 mg three times daily for 5 days, and a combined oral contraceptive pill once daily for 21 days, both starting from the first day of menses for 12 consecutive cycles. Patients in group D, had the levonorgestrel-releasing intrauterine system inserted into the uterine cavity. The insertion was done by a skilled gynecologist as an outpatient procedure without anesthesia. The possible long- and short-term side effects of the different interventions were carefully discussed with all patients, and those who were willing to participate had signed the informed consent before participation. The primary outcome was the improvement of postmenstrual spotting as reported by the patients in their menstrual diary at each of the follow up visits (three, six, nine and twelve months) after enrolment in the study.

The participants were asked to complete the menstrual diary card that was designed based on that used in the study of Johannes and colleagues in 1996. The illustrated symbols at the top of the card indicated the heaviness of menstrual bleeding (flooding, heavy, normal, light or spotting) and the names of the months were written on the left side of the card.

Study Design

Study Type:

Interventional

Actual Enrollment :

158 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Nonsurgical Management of Cesarean Scar Niche Related Abnormal Uterine Bleeding

Actual Study Start Date :

Mar 1, 2019

Actual Primary Completion Date :

Oct 20, 2022

Actual Study Completion Date :

Oct 20, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Tranexamic acid Patients in group A, received Tranexamic acid 1300 mg (2 tablets of 650 mg) three times daily for 5 days starting from the first day of menses for 12 months.	Drug: Tranexamic acid, Oral contraceptive pills and the Levonorgestrel-releasing intrauterine system. Comparing three different nonsurgical management options for abnormal uterine bleeding caused by cesarean scar niche.
Active Comparator: Combined oral contraceptive pill Patients in group B, received combined oral contraceptive pill (OCP) once daily for 21 days (Desogestrel 150 micrograms/ Ethinylestradiol 30 micrograms, tablets), starting from the first day of menses, then to have a one-week pill free period to allow for a withdrawal bleed, and that was repeated for 12 cycles.	Drug: Tranexamic acid, Oral contraceptive pills and the Levonorgestrel-releasing intrauterine system. Comparing three different nonsurgical management options for abnormal uterine bleeding caused by cesarean scar niche.
Active Comparator: Tranexamic acid plus Combined oral contraceptive pill Patients in group C, received a combination of Tranexamic acid 1300 mg three times daily for 5 days, and a combined oral contraceptive pill once daily for 21 days (Desogestrel 150 micrograms/ Ethinylestradiol 30 micrograms, tablets), both starting from the first day of menses for 12 consecutive cycles.	Drug: Tranexamic acid, Oral contraceptive pills and the Levonorgestrel-releasing intrauterine system. Comparing three different nonsurgical management options for abnormal uterine bleeding caused by cesarean scar niche.
Active Comparator: Levonorgestrel-releasing intrauterine system Patients in group D, had the levonorgestrel-releasing intrauterine system inserted into the uterine cavity. The insertion was done by a skilled gynecologist as an outpatient procedure without anesthesia.	Drug: Tranexamic acid, Oral contraceptive pills and the Levonorgestrel-releasing intrauterine system. Comparing three different nonsurgical management options for abnormal uterine bleeding caused by cesarean scar niche.

Outcome Measures

Primary Outcome Measures

Improvement of post-menstrual spotting [12 months]
Improvement of post-menstrual spotting as reported by the patients in their menstrual diary at each of the follow up visits (three, six, nine and twelve months) after enrolment in the study.

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 40 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

The study included 158 patients aged between 20 and 40 years who had a history of at least one caesarean delivery and presented with abnormal uterine bleeding in the form of postmenstrual spotting defined as bloody or brownish discharge of more than two days after the end of menstruation, with the total duration of (menses and spotting) of more than 7 days, or intermenstrual bleeding that starts after the end of the menses, who were diagnosed to have a caesarean scar niche by saline infusion sonography. Cesarean scar niche was defined as an anechoic triangular indentation at the site of the previous cesarean scar with a depth of at least 2 mm. Saline infusion sonography was done, in which instillation of saline solution into the uterine cavity, enhanced the transvaginal ultrasonographic image by providing a sonolucent contrast medium to allow for better visualization and delineation of the defect. Evaluation was performed according to the 2019 modified Delphi procedure where the basic evaluation of CS niche included measurements of the length, depth and width of the defect, the residual myometrial thickness (RMT) and the adjacent myometrial thickness (AMT). All measurements were made in the sagittal plane except the width which was measured in the transverse plane. The 4.5 MHz endovaginal transducer was used.

Exclusion Criteria:

Exclusion criteria were: pregnancy, desire for fertility within one year of enrolment in the study, any medical condition contraindicating the use of combined oral contraceptive pills, history of abnormal uterine bleeding dating before the last caesarean section, use of any hormonal treatment 3 months prior to enrolment, coagulopathy, and organic causes of bleeding like uterine fibroids, adenomyosis or endometrial hyperplasia.