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Clinical Trial Details — Status: Withdrawn

Administrative data

NCT number NCT04289948
Other study ID # DHRD/2018/080
Secondary ID
Status Withdrawn
Phase Phase 1/Phase 2
First received
Last updated
Start date March 1, 2019
Est. completion date September 1, 2022

Study information

Verified date February 2020
Source University Hospitals of Derby and Burton NHS Foundation Trust
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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


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.


Recruitment information / eligibility

Status Withdrawn
Enrollment 0
Est. completion date September 1, 2022
Est. primary completion date June 1, 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Intervention

Drug:
Phage
The studies will be undertaken using a cocktail of at least 2-3 anti-staphylococcal phages produced by Intralytix Inc, Baltimore, Maryland, USA. The phages will be included in a gel designed for application directly to the wound surface and packaged in 5 ml single use tubes.

Locations

Country Name City State
United Kingdom University Hospitals Derby and Burton NHS Foundation Trust Derby Derbyshire

Sponsors (4)

Lead Sponsor Collaborator
University Hospitals of Derby and Burton NHS Foundation Trust BioPhage Theraputics Limited, Nottingham University Hospitals NHS Trust, Wellcome Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Work Package 1: To assess the safety of the use of anti-staphylococcal phages therapy on the wound bacterial microbiome of uninfected DFU's. - Safety : Clinically significant change in safety bloods, vital signs, Full Blood Count (FBC), renal function, C-Reactive protein (CRP), Liver function Tests (LFT)s, Adverse events 7 months
Primary Work Package 2 To compare the effect on the microbiome of empirical systemic antibiotic therapy alone (ESAT) versus ESAT plus phage therapy in ulcers complicated by mild or moderate infection as assessed by IDSA criteria 16 months
Primary Work Package 3 To compare the use of empirical systemic antibiotic therapy versus phage therapy in ulcers complicated by mild infection on the eradication of the infection as assessed by IDSA criteria. 16 months
Secondary Work Package 1: Safety of phage gel and overt toxic effect of phage gel. The following outcomes will be recorded at weekly intervals for 4 weeks from baseline:
Incidence of new infection
Number of days of antibiotic usage
Change in surface microbiome
Adverse events
Change in safety bloods, vital signs, FBC, renal function, CRP, LFTs
Wound status (clinical infection, area, depth, extent of surface slough, pain by VAS, peri ulcer appearance)
Patient well-being using a Visual Analogue Scale, 0-100mm.
Vital signs (Resting pulse and blood pressure (BP))
7 months
Secondary Work Package 1: • Impact on the bacterial microbiome of anti-staphylococcal phage gel and systemically chosen antibiotics. The following outcomes will be recorded at weekly intervals for 4 weeks from baseline:
Incidence of new infection
Number of days of antibiotic usage
Change in surface microbiome
Adverse events
Change in safety bloods, vital signs, FBC, renal function, CRP, LFTs
Wound status (clinical infection, area, depth, extent of surface slough, pain by VAS, peri ulcer appearance)
Patient well-being using a Visual Analogue Scale, 0-100mm.
Vital signs (Resting pulse and blood pressure (BP))
7 months
Secondary Work Package 2: Safety of phage gel and overt toxic effect of phage gel. The following outcomes will be recorded at weekly intervals for 4 weeks from baseline:
change in surface microbiome
Number of antibiotic-free days
Adverse events
Change in safety bloods, vital signs, FBC, renal function, CRP, LFTs
Wound status (clinical infection, area, depth, extent of surface slough, pain by VAS, peri ulcer appearance)
Patient well-being using a Visual Analogue Scale, 0-100mm.
Eradication of clinical evidence of the infection in the index ulcer at weeks 1, 2 and 3, and time to eradication
Healing of all ulcers and time to healing
Resting pulse and blood pressure (BP)
7 months
Secondary 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. The following outcomes will be recorded at weekly intervals for 4 weeks from baseline:
change in surface microbiome
Number of antibiotic-free days
Adverse events
Change in safety bloods, vital signs, FBC, renal function, CRP, LFTs
Wound status (clinical infection, area, depth, extent of surface slough, pain by VAS, peri ulcer appearance)
Patient well-being using a Visual Analogue Scale, 0-100mm.
Eradication of clinical evidence of the infection in the index ulcer at weeks 1, 2 and 3, and time to eradication
Healing of all ulcers and time to healing
Resting pulse and blood pressure (BP)
16 months
Secondary Work Package 2: Impact on the bacterial microbiome of systemically chosen antibiotics and of anti-staphylococcal phage gel. The following outcomes will be recorded at weekly intervals for 4 weeks from baseline:
change in surface microbiome
Number of antibiotic-free days
Adverse events
Change in safety bloods, vital signs, FBC, renal function, CRP, LFTs
Wound status (clinical infection, area, depth, extent of surface slough, pain by VAS, peri ulcer appearance)
Patient well-being using a Visual Analogue Scale, 0-100mm.
Eradication of clinical evidence of the infection in the index ulcer at weeks 1, 2 and 3, and time to eradication
Healing of all ulcers and time to healing
Resting pulse and blood pressure (BP)
16 months
Secondary Work Package 3: Safety of phage gel and overt toxic effect of phage gel. The following outcomes will be recorded at weekly intervals for 4 weeks from baseline:
Change in surface microbiome
Number of antibiotic-free days
Adverse events
Change in safety bloods, FBC, renal function, CRP, LFTs
Wound status (clinical infection, area, depth, extent of surface slough, pain by VAS, peri ulcer appearance)
Patient well-being using a Visual Analogue Scale, 0-100mm.
Eradication of clinical evidence of the infection in the index ulcer at weeks 1, 2 and 3, and time to eradication
Healing of all ulcers and time to healing
Resting pulse and blood pressure (BP)
16 months
Secondary 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. The following outcomes will be recorded at weekly intervals for 4 weeks from baseline:
Change in surface microbiome
Number of antibiotic-free days
Adverse events
Change in safety bloods, FBC, renal function, CRP, LFTs
Wound status (clinical infection, area, depth, extent of surface slough, pain by VAS, peri ulcer appearance)
Patient well-being using a Visual Analogue Scale, 0-100mm.
Eradication of clinical evidence of the infection in the index ulcer at weeks 1, 2 and 3, and time to eradication
Healing of all ulcers and time to healing
Resting pulse and blood pressure (BP)
16 months
Secondary Work Package 3: Impact on the bacterial microbiome of systemically chosen antibiotics and of anti-staphylococcal phage gel. The following outcomes will be recorded at weekly intervals for 4 weeks from baseline:
Change in surface microbiome
Number of antibiotic-free days
Adverse events
Change in safety bloods, FBC, renal function, CRP, LFTs
Wound status (clinical infection, area, depth, extent of surface slough, pain by VAS, peri ulcer appearance)
Patient well-being using a Visual Analogue Scale, 0-100mm.
Eradication of clinical evidence of the infection in the index ulcer at weeks 1, 2 and 3, and time to eradication
Healing of all ulcers and time to healing
Resting pulse and blood pressure (BP)
16 months
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