Clinical trial NCT05977491: Point-of-care Tests for Vaginal Discharge in Nepal
Official title: Randomized Controlled Trial in Nepal: Introducing Point-of-care Tests and Identifying Barriers to Reduce Antibiotics for Vaginal Discharge
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Vaginal Discharge
Sexually Transmitted Diseases
Keywords: antibiotic overtreatment
psychosomatic
domestic violence
anxiety and depression
chlamydia trachomatis
neisseria gonorrhoea
trichomonas vaginalis
bacterial vaginosis
process evaluation
point-of-care-test
Lead sponsor: Norwegian University of Science and Technology
Sponsor class: OTHER
Collaborators: name: Kathmandu University School of Medical Sciences
name: University of Oslo
name: Universiteit Antwerpen
First posted: 2023-08-04
Enrollment: 1500
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Three armed RCT.

1. Standard treatment
2. POCT result based treatment
3. POCT result based treatment plus patient education and addressing of anxiety, depression and domestic violence
Primary purpose: OTHER

Brief summary: 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 over-treatment 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 randomized in three groups:

* standard treatment according to current practice
* POCT result based treatment
* POCT result based treatment plus patient education and addressing of psycho social vulnerabilities

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 tests 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) the proportion of correcly pescribed antibiotics (as defined by gold-standard tests) C) 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 and available counseling for 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 and 2025.

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 over-treated 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.

Addition (22.09.2024): after the first 100 participants it was recognized, that sensitivity of the combination pH and whiff test was unacceptably low for TV for women with a high pH and negative whiff test. We will add another low cost, immunological POCT for TV for women with a high pH and a negative whiff test after the first half of participants has been enrolled. Based on our additional power calculation, we will have sufficient power to seperately analyse the diagnostic accuracy for TV both before and after the addition of this 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, woman screening positive for positive for anxiety, depression or domestic violence will be offered psychological counseling or referral to a crisis center Participants will be followed up telephonically after 1 and 4 months.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of participants prescribed antibiotics (excluding antifungals)
timeFrame: at inclusion
measure: Proportion of participant with correct antibiotic treatment
timeFrame: At the primary appointment for the individual included patient. Three periods: 1: Whole inclusion period, 17months.2. first half of participants without additional POCT for TV. 3- second half of participants with additional POCT for TV.
measure: Proportion of participants adhering to treatment recommendations
timeFrame: At telephonic follow up after 1 month and after 4 months
Secondary outcomes:
measure: Proportion of participants receiving POCT based treatment, on over the counter acquisition of medication, dependent on if they were offered counseling for anxiety and depression
timeFrame: At telephonic follow up 1 and 4 months after initial consultation
measure: Proportion of participants receiving POCT based treatment and offered counseling for domestic violence on on over the counter acquisition of medication
timeFrame: At telephonic follow up 1 and 4 months after initial consultation
measure: Proportion of participants reporting symptom improvement or deterioration regarding vaginal discharge, depending if they received counseling for anxiety and depression
timeFrame: At telephonic follow up 1 and 4 months after initial consultation
measure: Does the proportion of women screening positive for anxiety and/or depression change after consultation for vaginal discharge
timeFrame: comparing scores of the Hopkins Symptom Check list at inklusion to follow up score 4 months after inclusion for the last 400 included participants
measure: Proportion of participants receiving POCT based treatment and aquiring over the counter medication, depending on if they receieved educational information
timeFrame: At follow up 1 and 4 months after initial consultation
measure: Comparing mean patient satisfaction with consultation and treatment between all RCT arms
timeFrame: At follow up after 4 months
Other outcomes:
measure: Prevalence STIs and associated demographic and clinical findings
timeFrame: at enrollment
measure: Associations between self reported domestic violence, anxiety and depression and STI diagnosis
timeFrame: at enrollment
measure: Diagnostic accuracy for bacterial vaginosis(BV) and/or Trichomonas Vaginalis (TV) with pH and whiff test
timeFrame: First 500 participants at Dhulikhel Hospital and first 250 participants at ORC.
measure: Diagnostic accuracy of sequential screening for bacterial vaginosis (BV) and /or Trichomonas vaginalis (TV)
timeFrame: Second half of participants at Dhulikhel Hospital (participant 501 - 1000) and out-reach -centers (participantn1251-1500).
Locations:
city: Dhulikhel
country: Nepal
facility: Dhulikhel Hospital
state: Kavre
Study officials:
affiliation: Norwegian University for Science and Technology
name: Risa AM Lonnee-Hoffmann, PhD
role: PRINCIPAL_INVESTIGATOR
References: