Clinical trial NCT04289948: Assessing the Efficacy of Anti-staphylococcal Phages in the Management of Infected Foot Ulcers in Diabetes
Official title: Assessing the Efficacy of Anti-staphylococcal Phages in the Management of Infected Foot Ulcers in Diabetes
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Diabetes
Diabetic Foot
Diabetic Foot Infection
Keywords: Diabetes
Diabetic Foot Disease
Diabetic Foot Ulcer
Lead sponsor: University Hospitals of Derby and Burton NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Wellcome Trust
name: BioPhage Theraputics Limited
name: Nottingham University Hospitals NHS Trust
First posted: 2020-02-28
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Work Package 1: Observational cohort pilot safety study Work Package 2: Randomised, double-blind, placebo controlled pilot study Work Package 3: Observer-blind pilot RCT

Detailed description: Work Package 1

WP1 is a safety cohort pilot study targeting patients with DFU which are non-infected as determined by the IDSA criteria. 20 participants will be recruited from Diabetic Foot Clinic at the Royal Derby Hospital. Phage gel will be applied to the index ulcer after the first and second sets of measures at baseline, weeks 1, 2 and 3. Samples will be taken at baseline and weekly up to 4 weeks by surface swab and deep tissue sample for determination of bacterial colonisation using both conventional and genotypic (molecular) microbiological methods, prior to any IMP application.

Work Package 2

WP2 is a pilot double blind, placebo-controlled, randomised study targeting patients with mild or moderate infection of DFUs and comparing systemic antibiotic therapy plus phage gel against systemic antibiotics therapy plus placebo gel. A total of 50 participants from two centres (foot clinics at Royal Derby Hospital and City Campus, Nottingham University Hospitals NHS Trust) will be recruited. Phage gel or placebo will be applied to the index ulcer after the first and second sets of measures at baseline, weeks 1, 2 and 3. Samples will be taken at baseline and weekly up to 4 weeks by surface swab and deep tissue sample for determination of bacterial colonisation using both conventional and genotypic (molecular) microbiological methods

Work Package 3

WP3 is an observer-blind RCT targeting patients with mild diabetic foot infection by IDSA criteria and comparing phage gel with systemic antibiotics. A total of 50 participants from two centres (foot clinics at Royal Derby Hospital and City Campus, Nottingham University Hospitals NHS Trust) will be recruited. Those with moderately severe infections will be withheld from this work package because of the clinical and ethical issues associated with withholding antibiotics in those with a moderately severe infection.

Eligibility criteria: Inclusion Criteria:

1. Diabetes Mellitus according to WHO criteria
2. are aged 18 years or over
3. Additionally, patients must meet one of the following criteria to participate in the described Work Package:

   * Patients are only eligible for WP1 if they also have one or more DFUs (area 25mm2) below the malleoli without infection according to IDSA criteria that have been present for at least 4 weeks
   * Patients are only eligible for WP2 if they also have one or more DFUs (area 25mm2) below the malleoli with mild or moderate infection according to IDSA criteria that have been present for at least 4 weeks
   * Patients are only eligible for WP3 if they also have one or more DFUs (area 25mm2) below the malleoli with mild infection according to IDSA criteria that have been present for at least 4 weeks

Exclusion Criteria:

We will exclude patients who meet ANY of the following criteria:

1. with mental incapacity to give informed consent,
2. who have other major co-morbidities, which in the opinion of the investigator would mean that the patient would not be able to complete the study
3. with significant peripheral arterial disease (PAD): ABPI (ankle brachial pressure index) \<0.7,
4. Who have osteomyelitis defined by agreed clinical criteria
5. who are receiving treatment with systemic glucocorticoids or other immunosuppressants,
6. who have received systemic or topical antibiotics in the preceding 14 days,
7. who are judged to require parenteral administration of antibiotics,
8. Who have been previously recruited to an earlier part of the project
9. who are women of childbearing age who are at risk of conception
10. History of antibiotic hypersensitivity

Primary outcomes:
measure: Work Package 1: To assess the safety of the use of anti-staphylococcal phages therapy on the wound bacterial microbiome of uninfected DFU's.
timeFrame: 7 months
measure: Work Package 2
timeFrame: 16 months
measure: Work Package 3
timeFrame: 16 months
Secondary outcomes:
measure: Work Package 1: Safety of phage gel and overt toxic effect of phage gel.
timeFrame: 7 months
measure: Work Package 1: • Impact on the bacterial microbiome of anti-staphylococcal phage gel and systemically chosen antibiotics.
timeFrame: 7 months
measure: Work Package 2: Safety of phage gel and overt toxic effect of phage gel.
timeFrame: 7 months
measure: Work Package 2: Clinical benefit and patient well-being associated with adding phage gel to systemically chosen antibiotics compared to placebo in the management of mild or moderate infection.
timeFrame: 16 months
measure: Work Package 2: Impact on the bacterial microbiome of systemically chosen antibiotics and of anti-staphylococcal phage gel.
timeFrame: 16 months
measure: Work Package 3: Safety of phage gel and overt toxic effect of phage gel.
timeFrame: 16 months
measure: Work Package 3: Clinical benefit and patient well-being associated with phage gel therapy compared to systemically chosen antibiotics in the management of mild infection.
timeFrame: 16 months
measure: Work Package 3: Impact on the bacterial microbiome of systemically chosen antibiotics and of anti-staphylococcal phage gel.
timeFrame: 16 months
Other outcomes:
Locations:
city: Derby
country: United Kingdom
facility: University Hospitals Derby and Burton NHS Foundation Trust
state: Derbyshire
Study officials:
References: