Ignite Creation Date:
2024-05-06 @ 5:48 PM
Last Modification Date:
2024-10-26 @ 2:35 PM
Study NCT ID:
NCT05434104
Status:
UNKNOWN
Last Update Posted:
2022-10-13
First Post:
2022-05-27
Brief Title:
The LISA Lactoferrin InStead of AntibioticsAntifungals Feasibility Study
Sponsor:
St Georges University of London
Organization:
St Georges University of London
Study Overview
Official Title:
Is the Naturally Occurring Prebiotic Lactoferrin an Acceptable Alternative to AntibioticAntifungal Tablets for Women With Bacterial Vaginosis or Thrush
Status:
UNKNOWN
Status Verified Date:
2022-10
Last Known Status:
NOT_YET_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
LISA
Brief Summary:
Three-quarters of women have bacterial vaginosis BV or vaginal thrushcandida 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 cows 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 antibioticantifungal 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
Lactoferrin is a prebiotic protein derived from cows 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 antibioticantifungal 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 antibioticsantifungals for women with bacterial vaginosis or thrush Background Over 200000 women are affected by bacterial vaginosis BV or vaginal candidathrush 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 antibioticsantifungals 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 n57 or candida n57 confirmed on vaginal Gram stain After completing questionnaires and providing self-taken vaginal samples women will be randomly allocated 21 into intervention or control groups All women will be followed up with repeat samples and textonline questionnaires after 1234 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 pessariestablets
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 antibioticsantifungals This allows for 24 women 21 either lost to follow up 12 recruited in general practice but not BVthrush 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 studys key feasibility outcomes 32
For example a recruitment rate of 50 114228 will have a 95 confidence interval of 435 to 565 and a follow-up rate of 80 91 114 will have a 95 confidence interval of 725 to 872
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 pessarytablet 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 21 to lactoferrinstandard treatment 6-19 12-week follow-up in clinic 11-20 qualitative evaluation 13-20 statisticalcostmicrobiome analyses 18-23 reportsdissemination
ImpactDissemination
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 rate50 follow-up 70 this could lead to a definitive trial which confirms that treating BVcandida 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
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 n57 or candida n57 confirmed on vaginal Gram stain After completing questionnaires and providing self-taken vaginal samples women will be randomly allocated 21 into intervention or control groups All women will be followed up with repeat samples and textonline questionnaires after 1234 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 pessariestablets
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 antibioticsantifungals This allows for 24 women 21 either lost to follow up 12 recruited in general practice but not BVthrush 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 studys key feasibility outcomes 32
For example a recruitment rate of 50 114228 will have a 95 confidence interval of 435 to 565 and a follow-up rate of 80 91 114 will have a 95 confidence interval of 725 to 872
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 pessarytablet 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 21 to lactoferrinstandard treatment 6-19 12-week follow-up in clinic 11-20 qualitative evaluation 13-20 statisticalcostmicrobiome analyses 18-23 reportsdissemination
ImpactDissemination
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 rate50 follow-up 70 this could lead to a definitive trial which confirms that treating BVcandida 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None