The LISA (Lactoferrin InStead of Antibiotics/Antifungals) Feasibility Study

NCT05434104 | Not Yet Recruiting

• 1 other identifier: 2021.0268
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 2

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 3 and 12-weeks all women will be invited back for a 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.

Conditions

Bacterial Vaginosis; Candida Vaginal

Keywords

lactoferrin; prebiotic

Outcome Measures

Primary Outcomes (4)

• The acceptability of vaginal lactoferrin treatment

  This will be assessed from interviews with 15-20 participants

  4-16 weeks after recruitment

• Adherence to treatment

  This will be assessed from participants' weekly count of remaining pessaries/tablets from questionnaires at 1, 2, 3 and 4 weeks

  During the first 4 weeks of the study

• Recruitment rate

  Investigators will record the percentage of eligible women who agree to take part

  Up to 15 months

• Follow-up rate

  Investigators will record the percentage of randomised women who are followed up after 12 weeks

  Up to 20 months

Secondary Outcomes (6)

• 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.

  4-16 weeks after recruitment

• Adverse events such as nausea, vomiting, vaginal irritation, abdominal pain, rashes, diarrhoea

  Between recruitment and 12 week follow up

• Recurrence or persistence of infection by 12 weeks

  At 12 week follow up

• Feasibility of obtaining data on healthcare use

  Last 6 months of study

• Percentage of participants who complete weekly symptom questionnaires for the first four weeks after recruitment.

  During the 12 weeks after recruitment

Study Arms (2)

Lactoferrin intervention group

EXPERIMENTAL

Women will be given bovine lactoferrin 300mg vaginal pessaries to insert every evening for the first 21 days of the study \[25\].

Other: Vaginal lactoferrin

Usual care control - standard oral antibiotics/antifungals

ACTIVE COMPARATOR

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.

Drug: Usual care

Interventions

Vaginal lactoferrin OTHER

Lactoferrin vaginal pessaries to insert nightly for 21 nights

Also known as: Difesan vaginal pessaries

Lactoferrin intervention group

Usual care DRUG

Women with bacterial vaginosis will be given oral metronidazole and women with vaginal candida will be given oral fluconazole

Also known as: Oral metronidazole or fluconazole

Usual care control - standard oral antibiotics/antifungals

Eligibility Criteria

• Age: 16 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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)

Sponsors & Collaborators

• King's College London: collaborator
• Guy's and St Thomas' NHS Foundation Trust: lead
• Statens Serum Institut: collaborator

Study Sites (2)

St Thomas' NHS Trust

London, se1 7eh, United Kingdom

Location

St George's, University of London

London, SW17 ORE, United Kingdom

Location

MeSH Terms

Conditions

Vaginosis, Bacterial; Candidiasis, Vulvovaginal

Interventions

Metronidazole; Fluconazole

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Vaginitis; Vaginal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Candidiasis; Mycoses; Vulvovaginitis; Vulvitis; Vulvar Diseases

Intervention Hierarchy (Ancestors)

Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Triazoles

Study Officials

• Pippa Oakeshott, MD

  St George's, University of London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pippa Oakeshott, MD

CONTACT

020 8725 0153; oakeshot@sgul.ac.uk

Fiona Reid, MSc

CONTACT

fiona.reid@kcl.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: open label randomised feasibility study over 12 weeks with qualitative, economic and microbiological evaluations.

Study Record Dates

• First Submitted: May 27, 2022
• First Posted: June 27, 2022
• Study Start: March 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)