The LISA (Lactoferrin InStead of Antibiotics/Antifungals) Feasibility Study (LISA)
Primary Purpose
Bacterial Vaginosis, Candida Vaginal
Status
Not yet recruiting
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Vaginal lactoferrin
Usual care
Sponsored by
About this trial
This is an interventional health services research trial for Bacterial Vaginosis focused on measuring lactoferrin, prebiotic
Eligibility Criteria
Inclusion Criteria:
Aged 16-49 years
- Having periods (apart from women with a Mirena IUCD or polycystic ovary syndrome)
- Ability to consent
- Clinical diagnosis of BV or thrush confirmed on Gram stain
- Willing to be randomised to vaginal lactoferrin pessaries or oral antibiotics/antifungals
- Agrees to provide vaginal samples at home and post/deliver them back to the research team.
- Agrees to avoid douching during the study (as this can flush out lactobacilli needed for a healthy microbiome).
Exclusion Criteria:
- Pregnant or breast feeding
- Currently has chlamydia, gonorrhoea or trichomonas (as treatment for these would affect the results).
- Known allergy to metronidazole or azoles
- Post-menopausal (because of diagnostic confusion between atrophic vaginitis and bacterial vaginosis)
Sites / Locations
- St Thomas' NHS Trust
- St George's, University of London
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Lactoferrin intervention group
Usual care control - standard oral antibiotics/antifungals
Arm Description
Women will be given bovine lactoferrin 300mg vaginal pessaries to insert every evening for the first 21 days of the study [25].
Control women with BV will be given oral metronidazole 400mg twice daily for five days (and routine advice about avoiding alcohol). Control women with candida will be given a fluconazole 150mg capsule to take orally the same day.
Outcomes
Primary Outcome Measures
The acceptability of vaginal lactoferrin treatment
This will be assessed from interviews with 15-20 participants
Adherence to treatment
This will be assessed from participants' weekly count of remaining pessaries/tablets from questionnaires at 1, 2, 3 and 4 weeks
Recruitment rate
Investigators will record the percentage of eligible women who agree to take part
Follow-up rate
Investigators will record the percentage of randomised women who are followed up after 12 weeks
Secondary Outcome Measures
Acceptability of study procedures, and whether participants think other women would be willing to take part in a future randomised trial of lactoferrin versus oral antibiotics.
Investigators will conduct telephone interviews between 4 and 16 weeks after recruitment with 15-20 participants
Adverse events such as nausea, vomiting, vaginal irritation, abdominal pain, rashes, diarrhoea
Investigators will ask about adverse events during weekly text questionnaires during the first four weeks and on the final questionnaire at 12 weeks follow up
Recurrence or persistence of infection by 12 weeks
Investigators will ask about symptoms of infection on the final 12 week questionnaire and assess infection status by analysis of self-taken vaginal samples
Feasibility of obtaining data on healthcare use
This will be assessed by comparing reported healthcare use in final 12 week questionnaires with a medical record search in 30 participants
Percentage of participants who complete twice weekly symptom questionnaires for the first four weeks after recruitment.
This will be assessed from analysis of questionnaires.
Percent of self-taken samples suitable for microbiological analysis
This will be assessed from microbiological analysis of self-taken vaginal samples
Full Information
NCT ID
NCT05434104
First Posted
May 27, 2022
Last Updated
October 11, 2022
Sponsor
St George's, University of London
Collaborators
King's College London, Statens Serum Institut
1. Study Identification
Unique Protocol Identification Number
NCT05434104
Brief Title
The LISA (Lactoferrin InStead of Antibiotics/Antifungals) Feasibility Study
Acronym
LISA
Official Title
Is the Naturally Occurring Prebiotic Lactoferrin an Acceptable Alternative to Antibiotic/Antifungal Tablets for Women With Bacterial Vaginosis or Thrush?
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 2022 (Anticipated)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
June 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
St George's, University of London
Collaborators
King's College London, Statens Serum Institut
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Three-quarters of women have bacterial vaginosis (BV) or vaginal thrush/candida yeast infection at least once during their lifetime. Symptoms can include abnormal vaginal discharge, soreness, itching and an unpleasant smell. BV during pregnancy can make the baby come too early. In the UK over a million women suffer recurrent vaginal infections. These can affect their sexual relationships and quality of life, and may need repeated courses of treatment. But some women prefer not to keep taking antibiotics which can have side effects and encourage the growth of resistant superbugs.
Lactoferrin is a prebiotic protein derived from cow's milk. Women also have naturally occurring lactoferrin in their vagina where it helps to prevent infections and encourage the growth of healthy bacteria. Recent research suggests lactoferrin may be an effective treatment for BV and thrush, but this needs to be confirmed.
Aim To see if it is feasible to conduct a future trial to prove whether lactoferrin vaginal pessaries are an acceptable, effective and cost-effective alternative to antibiotic tablets for women with BV or thrush.
Methods The investigators will recruit a total of 57 women with BV and 57 with thrush from two sexual health clinics and a general practice. Women will be asked to provide self-taken vaginal samples with a cotton bud, and to complete a confidential sexual-health questionnaire. Then the women will be divided into two groups. One group will be given lactoferrin vaginal pessaries to use every night for 3-weeks. The other group will be given antibiotic/antifungal tablets. All women will be asked to provide repeat vaginal samples at home and text us about any symptoms to see if the treatment works, if the infection comes back and if they would like antibiotics. After 12-weeks all women will be invited back for a final check-up.
Outcome measures:
Acceptability and use of vaginal lactoferrin - from questionnaires, and interviews with 15-20 women
Recruitment and follow-up rates
Cost of lactoferrin treatment
The percentage of women who report their symptoms have resolved after a week
How quickly infections clear or recur - from analysis of samples
Patient benefit:
If this study leads to a trial showing vaginal lactoferrin is an acceptable and effective alternative to antibiotics, this could help relieve symptoms, prevent antimicrobial resistance and save NHS costs.
Detailed Description
Research Question: Is it feasible to conduct a future trial to investigate if Lactoferrin is an acceptable alternative to oral antibiotics/antifungals for women with bacterial vaginosis or thrush? Background Over 200,000 women are affected by bacterial vaginosis (BV) or vaginal candida/thrush each year in England. A million women suffer recurrent infections which many find distressing. The infections may also be associated with HIV infection and adverse pregnancy outcomes. Although BV and candida can be treated with oral antibiotics/antifungals, these can have side effects and encourage the development of antimicrobial resistance, a major global health problem.
Lactoferrin is a naturally occurring prebiotic protein present in the vagina where it helps to prevent infections and normalise the vaginal microbiome. It has been used to treat refractory BV and may also be effective against candida, but more evidence is needed.
Objective To see if it is feasible to conduct a future, definitive trial in women with BV or candida to investigate if vaginal lactoferrin pessaries are as effective as oral antibiotics in resolving symptoms, preventing recurrent infection and producing a healthy lactobacilli-dominated vaginal microbiome.
Design: open label randomised feasibility study over 12 weeks with qualitative, economic and microbiological evaluations.
Setting: a sexual health clinic and a general practice
Population 114 women with genitourinary symptoms and BV (n=57) or candida (n=57) confirmed on vaginal Gram stain. After completing questionnaires and providing self-taken vaginal samples women will be randomly allocated 2:1 into intervention or control groups. All women will be followed up with repeat samples and text/online questionnaires after 1,2,3,4 and 12 weeks.
Intervention 38 women with BV and 38 women with candida will be given vaginal 300mg lactoferrin pessaries to insert nightly for 21 nights
Comparator 19 women with BV will be given metronidazole 400mg twice daily for 5-days, and 19 women with candida will be given a fluconazole 150mg capsule.
Outcomes
Acceptability of vaginal lactoferrin - from questionnaires, and interviews
Adherence to treatment (from participants' weekly count of remaining pessaries/tablets)
Recruitment rate and willingness of women to be randomised
Follow-up rate
Acceptability of study procedures such as providing vaginal samples and responding to texts about symptoms.
Adverse events
Estimate of the cost of lactoferrin and the feasibility of obtaining data on healthcare use
Percentage of participants who complete twice weekly symptom questionnaires and provide self-taken vaginal samples at home which are suitable for microbiological analyses. These findings will inform the design of a future definitive trial.
Masking
This is an open label trial and there will be no blinding to treatment allocation of the participants or researchers. However, the analysis of samples (Gram stain and microbiome analysis) will be done blind to treatment allocation [1].
Sample size calculations and analysis
We will recruit 114 women in order to achieve a final sample of 90 followed-up women at 12-weeks (30 with BV given lactoferrin, 30 with candida given lactoferrin, and 30 controls (15 with BV, 15 candida) given oral antibiotics/antifungals. This allows for 24 women (21%) either lost to follow up (12%), recruited in general practice but not BV/thrush on Gram stain (4%) or given antibiotics for an STI (3%) an unrelated reason (2%, eg dental abscess) as antibiotics may affect both symptoms and the vaginal microbiome. Sixty intervention women and 30 controls is consistent with numbers recommended by Teare et al for feasibility studies and will provide an acceptable level of precision around the study's key feasibility outcomes [32].
For example, a recruitment rate of 50% (114/228) will have a 95% confidence interval of 43.5% to 56.5%; and a follow-up rate of 80% (91 /114) will have a 95% confidence interval of 72.5% to 87.2%.
Each week the sexual health specialist investigator sees an average of six eligible women in his recurrent vaginitis clinic and the general practitioner investigator sees one or two in general practice. PPI work and our previous trials suggest ≥50% of eligible women will agree to participate [26, 27]. If we recruit an average of 3 women a week (two in clinic, one in GP) we should complete recruitment of 114 women within 38 weeks. We will allow 12 months.
Analysis of quantitative study outcomes will be descriptive. Numbers and percentages will be presented, along with 95% confidence intervals. Weekly pessary/tablet counts will be presented as mean (SD) or median (IQR) as appropriate. Numbers of adverse events and number of women with adverse events will be summarised. The flow of participants through the study will be presented in a CONSORT diagram.
Timetable (months)
1-2 set-up 3-14 recruit 114 women and randomise 2:1 to lactoferrin/standard treatment 6-19 12-week follow-up in clinic 11-20 qualitative evaluation 13-20 statistical/cost/microbiome analyses 18-23 reports/dissemination
Impact/Dissemination
Study findings will be published in high impact journals and widely publicised. If progression criteria are met, (lactoferrin is acceptable to ≥70% of women, recruitment rate≥50%, follow-up ≥70%,) this could lead to a definitive trial which confirms that treating BV/candida with lactoferrin is an acceptable, effective, safe and cost-effective alternative to antibiotics. This could benefit women by reducing their use of antibiotics, preventing recurrent infections and decreasing the spread of antimicrobial resistance.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bacterial Vaginosis, Candida Vaginal
Keywords
lactoferrin, prebiotic
7. Study Design
Primary Purpose
Health Services Research
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
open label randomised feasibility study over 12 weeks with qualitative, economic and microbiological evaluations.
Masking
Outcomes Assessor
Masking Description
This is an open label trial and there will be no blinding to treatment allocation of the participants or researchers. However, the analysis of samples (Gram stain and microbiome analysis) will be done blind to treatment allocation
Allocation
Randomized
Enrollment
114 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Lactoferrin intervention group
Arm Type
Experimental
Arm Description
Women will be given bovine lactoferrin 300mg vaginal pessaries to insert every evening for the first 21 days of the study [25].
Arm Title
Usual care control - standard oral antibiotics/antifungals
Arm Type
Active Comparator
Arm Description
Control women with BV will be given oral metronidazole 400mg twice daily for five days (and routine advice about avoiding alcohol). Control women with candida will be given a fluconazole 150mg capsule to take orally the same day.
Intervention Type
Other
Intervention Name(s)
Vaginal lactoferrin
Other Intervention Name(s)
Difesan vaginal pessaries
Intervention Description
Lactoferrin vaginal pessaries to insert nightly for seven nights
Intervention Type
Drug
Intervention Name(s)
Usual care
Other Intervention Name(s)
Oral metronidazole or fluconazole
Intervention Description
Women with bacterial vaginosis will be given oral metronidazole and women with vaginal candida will be given oral fluconazole
Primary Outcome Measure Information:
Title
The acceptability of vaginal lactoferrin treatment
Description
This will be assessed from interviews with 15-20 participants
Time Frame
4-16 weeks after recruitment
Title
Adherence to treatment
Description
This will be assessed from participants' weekly count of remaining pessaries/tablets from questionnaires at 1, 2, 3 and 4 weeks
Time Frame
During the first 4 weeks of the study
Title
Recruitment rate
Description
Investigators will record the percentage of eligible women who agree to take part
Time Frame
Up to 15 months
Title
Follow-up rate
Description
Investigators will record the percentage of randomised women who are followed up after 12 weeks
Time Frame
Up to 20 months
Secondary Outcome Measure Information:
Title
Acceptability of study procedures, and whether participants think other women would be willing to take part in a future randomised trial of lactoferrin versus oral antibiotics.
Description
Investigators will conduct telephone interviews between 4 and 16 weeks after recruitment with 15-20 participants
Time Frame
4-16 weeks after recruitment
Title
Adverse events such as nausea, vomiting, vaginal irritation, abdominal pain, rashes, diarrhoea
Description
Investigators will ask about adverse events during weekly text questionnaires during the first four weeks and on the final questionnaire at 12 weeks follow up
Time Frame
Between recruitment and 12 week follow up
Title
Recurrence or persistence of infection by 12 weeks
Description
Investigators will ask about symptoms of infection on the final 12 week questionnaire and assess infection status by analysis of self-taken vaginal samples
Time Frame
At 12 week follow up
Title
Feasibility of obtaining data on healthcare use
Description
This will be assessed by comparing reported healthcare use in final 12 week questionnaires with a medical record search in 30 participants
Time Frame
Last 6 months of study
Title
Percentage of participants who complete twice weekly symptom questionnaires for the first four weeks after recruitment.
Description
This will be assessed from analysis of questionnaires.
Time Frame
During the 12 weeks after recruitment
Title
Percent of self-taken samples suitable for microbiological analysis
Description
This will be assessed from microbiological analysis of self-taken vaginal samples
Time Frame
During the 12 weeks after recruitment
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Aged 16-49 years
Having periods (apart from women with a Mirena IUCD or polycystic ovary syndrome)
Ability to consent
Clinical diagnosis of BV or thrush confirmed on Gram stain
Willing to be randomised to vaginal lactoferrin pessaries or oral antibiotics/antifungals
Agrees to provide vaginal samples at home and post/deliver them back to the research team.
Agrees to avoid douching during the study (as this can flush out lactobacilli needed for a healthy microbiome).
Exclusion Criteria:
Pregnant or breast feeding
Currently has chlamydia, gonorrhoea or trichomonas (as treatment for these would affect the results).
Known allergy to metronidazole or azoles
Post-menopausal (because of diagnostic confusion between atrophic vaginitis and bacterial vaginosis)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Pippa Oakeshott, MD
Phone
020 8725 0153
Email
oakeshot@sgul.ac.uk
First Name & Middle Initial & Last Name or Official Title & Degree
Fiona Reid, MSc
Email
fiona.reid@kcl.ac.uk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pippa Oakeshott, MD
Organizational Affiliation
St George's, University of London
Official's Role
Principal Investigator
Facility Information:
Facility Name
St Thomas' NHS Trust
City
London
ZIP/Postal Code
se1 7eh
Country
United Kingdom
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Phillip Hay, FRCP
Email
phillip.Hay@gstt.nhs.uk
Facility Name
St George's, University of London
City
London
ZIP/Postal Code
SW17 ORE
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
The LISA (Lactoferrin InStead of Antibiotics/Antifungals) Feasibility Study
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