Point-of-care Tests for Vaginal Discharge in Nepal (POCT-BRA)

Randomized Controlled Trial in Nepal: Introducing Point-of-care Tests and Identifying Barriers to Reduce Antibiotics for Vaginal Discharge

The goal of this clinical trial is to examine if and how the implementation of point-of care-tests (POCT) for sexually transmitted infections in the management of abnormal vaginal discharge reduces the overtreatment with antibiotics in a low income country. The setting is a university hospital in a semi-rural area in Nepal and several of its rural out-reach-centers. The plan is to include 1500 women attending the gynecological outpatients with a problem of vaginal discharge over approximately a one year period.

The main questions the clinical trial aims to answer are:

• Does POCT guided treatment result in reduced overtreatment of antibiotics, compared to the current approach in Nepal?
• What are the barriers and facilitators of the acceptability of POCTs and the resulting treatment from the perspective of both patients and health care practitioners?

Participants will be randomised in three groups:

• standard treatment according to current practice
• POCT result based treatment
• POCT result based treatment plus patient education and addressing of psychosocial vulnerabilities

Study Overview

• Status: Not yet recruiting
• Conditions: Sexually Transmitted Diseases; Vaginal Discharge
• Intervention / Treatment: Diagnostic test: Health care practitioner is informed of POCT results for CT and NG; Diagnostic test: Health care practitioner is informed about POCT result for TV and BV; Other: Health care practitioner is informed on result for anxiety, depression,domestic violence screening

Detailed Description

Abnormal vaginal discharge (AVD) is a common problem women seek treatment for allover the world. In low and low- middle income countries (LLMICs) about one third of these women will have a sexually transmitted disease (STI) caused by Chlamydia trachomatis (CT), Neisseria gonorrhoea (NG) or Trichomonal vaginalis (TV). Approximately another third will have an imbalance in the vaginal microbiotic flora, bacterial vaginosis (BV). These women and their sexual partners in the case of sexually transmitted diseases will benefit from specific antibiotic treatment. The last third of women will not have any infection and there are indications that psychosocial problems may be expressed as somatic complaints, for example of abnormal vaginal discharge in some cultures.

In high income countries, with the help of laboratory-based tests, available after few days, treatment is usually with a narrow spectrum antibiotic for specific bacteria. This involves less risk for the development of antibiotic resistance. In low-income countries, laboratory testing is not feasible due to costs and logistics. Women are usually receiving antibiotic treatment with several types of antibiotics to cover STIs. More recently, point-of -care tests which are nearly as accurate as laboratory-based tests have been developed. Implementation studies for these tests in LLMICs are lacking. However, these molecular tests are still expensive.

In this study the investigators propose a combination of molecular tests for the two most serious infections (CT and NG) and a cheap and simple test for TV and BV, which both are treated with the same type of antibiotic.

In addition, women attending an outpatient department in a LLMIC setting, expect (antibiotic) treatment, which they will not receive with a negative POCT. In LLMICs it is common practice to purchase over the counter medication, inclusive antibiotics. In particular for women with negative POCT results, there could be a lack of adherence to treatment recommendations.

We want to examine the following research questions (RQ) in the context of treatment for vaginal discharge:

1. Can POCTs effectively reduce the use of antibiotics? A) The amount of antibiotics prescribed at the time of the appointment B) Additional antibiotics used, as reported by the patients,
2. Barriers and facilitators for patients and health practitioners with a focus on psychosocial and educational elements

For this purpose, a RCT with three arms was designed:

(A) Treatment as usual, (B) Treatment according to POCT results, (C) Treatment according to POCT results and additional patient information on vaginal discharge and antibiotics and screening for and attention by the attending health care practitioner to psychosocial problems.

The investigators plan to include 1500 women with the complaint of abnormal vaginal during a 10-12 month period at Dhulikhel hospital, a tertiary university hospital in central Nepal and selected outreach centers in 2024.

Sample size calculation are based on RQ1 and RQ2, feasibility of recruitment and the precision of the estimates, a two-sided 95 % confidence intervals (CI). For RQ1, the use of any antibiotics will be assessed in both POCT arms combined versus the treatment as usual arm (n = 1500), whilst the effect of the educational material on the use of over-the-counter medications will be assessed in the POCTplus versus the POCT group (n = 1000). As many as 85% of women with AVD are overtreated with antibiotics in LLMICs, around 50 % receive antimicrobial resistance driving antibiotics and it is expected, that around 40 % women in the POCT group will subsequently seek over the counter antibiotics. With 1500 participants randomized 1:1:1, a 10 to 20 percentage point reduction in any of these measures will produce CIs with a width between 8 and 12 % and at least 90% power. When allowing for around 40 % loss to follow-up, when assessing the use of over-the-counter antibiotics, the expected width of the CI is still around 15 %.

The investigators will collect self-sampled urine and vaginal swabs from all included women and a self-administered questionnaire with a color-coded audio-computer. The questionnaire contains demographic information and a validated tool to screen for anxiety, depression and domestic violence.

Gold standard testing for the STIs and BV will be performed on all women. Participants will be randomized into three arms. In the standard treatment arm, the attending health practitioner will not be informed about POCT results. In the two POCT arms, the health care practitioner will be informed about CT and NG status and about the pH, inclusive a confirmatory whiff test.

In the POCT-PLUS arm, patients will receive additional educational information about physiological and abnormal vaginal discharge and about potentially negative effects of antibiotic treatment. In this arm, health care practitioners will be informed if the woman screened positive for anxiety, depression or domestic violence.

Participants will be followed up telephonically after 1 and 4 months.

• Study Type: Interventional
• Enrollment (Estimated): 1500
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Risa AM Lonnee-Hoffmann, PhD; Phone Number: 004741482354; Email: risa.lonnee-hoffmann@ntnu.no
• Study Contact Backup: Name: Sunila Shakya, PhD; Phone Number: 009779803972599; Email: sunilashakya@kusms.edu.np

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Women presenting with vaginal discharge to gynecological outpatients

Exclusion Criteria:

• Minors below the age of 18 years.
• Any bleeding from the vagina.
• Suspicion of gynecological cancer.
• Previous inclusion in the same study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard treatment; Patients are treated by the health care practitioner according to local protocol. This protocol corresponds to the syndromic approach without laboratory or microscopic testing. This may or may not include inspection and examination of the vulva, vagina, cervix and lower abdomen.
Active Comparator: POCT based treatment; The health care practitioner is informed about the POCT results for CT and NG (positive or negative). In addition, if the pH is within the normal level (4.5 and below). If it is higher, he will receive the outcome of the whiff test (positive or negative). Examination of the patient is performed according to the discretion of the health care practitioner.	Diagnostic test: Health care practitioner is informed of POCT results for CT and NG; Molecular, PCR based near-POCT performed by the research assistant on self -collected urine. The outcome is positive or negative; Other Names: GeneXpert test from Cepheid for CT andNG; Diagnostic test: Health care practitioner is informed about POCT result for TV and BV; The pH of vaginal secretion is measured from a self-collected swab by the research assistant, and if above 4.5 a dropp of KOH is added. If it smells fishy, the whiff test is positive.; Other Names: Narrow range pH and confirmatory whiff test with potassium hydroxide (KHO), Amsel criteria
Active Comparator: POCT based treatment PLUS; Same as in POCT based treatment PLUS: Patients are given a short educational leaflet and 10 min audio-recording about physiological and abnormal vaginal discharge and about problems associated with unnecessary use of antibiotics.; All women complete a questionnaire prior to examination, including a screening tool for anxiety and depression and domestic violence. If they screen positive, the health care practitioner will be informed, in addition to the POCT result.	Diagnostic test: Health care practitioner is informed of POCT results for CT and NG; Molecular, PCR based near-POCT performed by the research assistant on self -collected urine. The outcome is positive or negative; Other Names: GeneXpert test from Cepheid for CT andNG; Diagnostic test: Health care practitioner is informed about POCT result for TV and BV; The pH of vaginal secretion is measured from a self-collected swab by the research assistant, and if above 4.5 a dropp of KOH is added. If it smells fishy, the whiff test is positive.; Other Names: Narrow range pH and confirmatory whiff test with potassium hydroxide (KHO), Amsel criteria; Other: Health care practitioner is informed on result for anxiety, depression,domestic violence screening; The research assistant will inform the health care practitioner if screening positive for anxiety, depression or domestic violence.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amount of prescribed antibiotics (excluding antifungals)	Comparing the proportion of women prescribed antibiotics for treatment in total and in subgroups, depending if the health care practitioner was informed about the POCT results. Self reported by the health care practitioner. Subgroups: Doxycycline, Tetracycline, Ciprofloxacin, Azithromycin or Trimethoprim(sulfa), Metronidazole, Cephalosporin, other antibiotics.	At the primary appointment for the individual included patient. During inclusion (10-12 months), for the trial.
Antimicrobial resistance driving antibiotics prescribed	Comparing the proportion of women prescribed antimicrobial resistance driving antibiotics, in total and in subgroups (Cephalosporins, Azithromycin, Ciprofloxacin), depending if the health care practitioner was informed about the POCT results. Reported by health care practitioner.	At the primary appointment for the individual included patient. During inclusion (10-12 months), for the trial.
Adherence to treatment recommendations	Comparing the proportion of women reporting acquisition of self reported over the counter medication in total and subgroups (antibiotics, painkillers, others, unknown type) for the three different RCT arms.	At telephonic follow up after 1 month.
Adherence to treatment recommendations	Comparing the proportion of women reporting acquisition of over the counter medication in total and subgroups (antibiotics, painkillers, others, unknown type) for the three different RCT arms.	At telephonic follow up after 4 months
Correct antibiotic treatment	Comparing the proportion of women receiving correct antibiotic treatment for a Chlamydia trachomatis, Neisseria gonorrhoea, Trichomonas vaginalis infection or for bacterial vaginosis, depending if the health practitioner received POCT results.	At the primary appointment for the individual included patient. During inclusion (10-12 months), for the trial.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of educational measures on over the counter acquisition of medication	Comparing the proportion of patients buying over the counter medication in total and subgroups, depending if they received education on vaginal discharge and antibiotics. Subgroups: Antibiotics, painkillers, others, unknown type.	At follow up 1 and 4 months after initial consultation
Effect of screening for anxiety and depression on over the counter acquisition of medication	Comparing the proportion of patients buying over the counter medication in total and subgroups, depending if the health practitioner was informed about a positive anxiety or depression screen. Subgroups: Antibiotics, painkillers, others, unknown type.	At follow up 1 and 4 months after initial consultation
Effect of addressing domestic violence on over the counter acquisition of medication	Comparing the proportion of patients buying over the counter medication in total and subgroups, depending if the health practitioner was informed about a history of domestic violence. Subgroups: Antibiotics, painkillers, others, unknown type.	At follow up 1 and 4 months after initial consultation
Patient satisfaction	Satisfaction with consultation and treatment on a scale from 1-10	At follow up after 4 months

Collaborators and Investigators

• Sponsor: Norwegian University of Science and Technology
• Collaborators: University of Oslo; Kathmandu University School of Medical Sciences; Universiteit Antwerpen
• Investigators: Principal Investigator: Risa AM Lonnee-Hoffmann, PhD, Norwegian University for Science and Technology

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2024
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): April 30, 2025

Study Registration Dates

• First Submitted: July 4, 2023
• First Submitted That Met QC Criteria: July 26, 2023
• First Posted (Actual): August 4, 2023

Study Record Updates

• Last Update Posted (Actual): August 4, 2023
• Last Update Submitted That Met QC Criteria: July 26, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: domestic violence; bacterial vaginosis; chlamydia trachomatis; psychosomatic; process evaluation; anxiety and depression; trichomonas vaginalis; antibiotic overtreatment; neisseria gonorrhoea; point-of-care-test
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Communicable Diseases; Disease Attributes; Vaginal Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Sexually Transmitted Diseases; Vaginal Discharge
• Other Study ID Numbers: 335889

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in the applicable article, after deidentification (without participant number) (text, tables, figures,and appendices).
• IPD Sharing Time Frame: Immediately following publication. For five years
• IPD Sharing Access Criteria: To researchers who submit a sound proposal. Proposals should be directed to risa.lonnee-hoffmann@ntnu.no. To gain access, data requestors will need to sign a data access agreement. Data are available for 5 years at a third party website (Linkto be included).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• 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.: No