DiabetesPhase 1/2PDFINCT04289948
Assessing the Efficacy of Anti-staphylococcal Phages in the Management of Infected Foot Ulcers in Diabetes
A Phase 1/2 study testing Phage in people with Diabetes and Diabetic Foot, run by University Hospitals of Derby and Burton NHS Foundation Trust at 1 site in United Kingdom.
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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetes, Diabetic Foot, Diabetic Foot Infection
- What is being tested?
- Phage
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Mar 2019to 1 Sep 2022
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diabetes Mellitus according to WHO criteria
- are aged 18 years or over
- 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
Who cannot join
- We will exclude patients who meet ANY of the following criteria:
- with mental incapacity to give informed consent,
- 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
- with significant peripheral arterial disease (PAD): ABPI (ankle brachial pressure index) <0.7,
- Who have osteomyelitis defined by agreed clinical criteria
- who are receiving treatment with systemic glucocorticoids or other immunosuppressants,
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- who have received systemic or topical antibiotics in the preceding 14 days,
- who are judged to require parenteral administration of antibiotics,
- Who have been previously recruited to an earlier part of the project
- who are women of childbearing age who are at risk of conception
- History of antibiotic hypersensitivity
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University Hospitals Derby and Burton NHS Foundation Trust
Derby, Derbyshire, DE22 3DT
About this study
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
Read the 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.
- Conditions
- Diabetes, Diabetic Foot, Diabetic Foot Infection
- Being tested
- Phage
- Keywords
- Diabetes, Diabetic Foot Disease, Diabetic Foot Ulcer
- Medical subject headings
- Diabetes Mellitus, Diabetic Foot
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PhageDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Phage | Experimental | Not described Receives: Drug: Phage |
| Placebo | Placebo comparator | Not described Receives: Drug: Phage |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 7 months
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
Measured: 16 months
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.
Measured: 16 months
Secondary outcomes (8)
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))
Measured: 7 months
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))
Measured: 7 months
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)
Measured: 7 months
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)
Measured: 16 months
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)
Measured: 16 months
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)
Measured: 16 months
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)
Measured: 16 months
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)
Measured: 16 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2020
- Study start1 Mar 2019 (estimated)
- Primary completion1 Jun 2022 (estimated)
- Study completion1 Sep 2022 (estimated)
Why it stopped: Funding issues meant that development of the study was halted.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospitals of Derby and Burton NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Wellcome Trust, BioPhage Theraputics Limited, Nottingham University Hospitals NHS Trust
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04289948
- Sponsor's protocol ID
- DHRD/2018/080
- Acronym
- PDFI
- Status last verified
- Feb 2020
- First submitted
- 3 Sep 2018
- Last updated
- 28 Feb 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessing the Efficacy of Anti-staphylococcal Phages in the Management of Infected Foot Ulcers in Diabetes
- ClinicalTrials.gov ID
- NCT04289948
- Acronym / sponsor ID
- PDFI / DHRD/2018/080
- Conditions
- Diabetes, Diabetic Foot, Diabetic Foot Infection
- Keywords
- Diabetes, Diabetic Foot Disease, Diabetic Foot Ulcer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Funding issues meant that development of the study was halted.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University Hospitals of Derby and Burton NHS Foundation TrustUniversity, hospital or other
- Collaborators
- Wellcome Trust, BioPhage Theraputics Limited, Nottingham University Hospitals NHS Trust
- Study start
- 1 Mar 2019 (estimated)
- Primary completion
- 1 Jun 2022 (estimated)
- Study completion
- 1 Sep 2022 (estimated)
- First posted
- 28 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phage | Experimental | Drug: Phage |
| Placebo | Placebo comparator | Drug: Phage |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Diabetes Mellitus according to WHO criteria
- are aged 18 years or over
- Additionally, patients must meet one of the following criteria to participate in the described Work Package:
Key exclusion criteria (11 listed)
- with mental incapacity to give informed consent,
- 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
- with significant peripheral arterial disease (PAD): ABPI (ankle brachial pressure index) <0.7,
- Who have osteomyelitis defined by agreed clinical criteria
- who are receiving treatment with systemic glucocorticoids or other immunosuppressants,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PhageThe 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. | Drug | Phage, Placebo |
Primary outcome
Work Package 1: To assess the safety of the use of anti-staphylococcal phages therapy on the wound bacterial microbiome of uninfected DFU's.
Time frame: 7 months
- 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
Work Package 2
Time frame: 16 months
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
Work Package 3
Time frame: 16 months
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.
8 secondary outcomes
Work Package 1: Safety of phage gel and overt toxic effect of phage gel.
Time frame: 7 months
Work Package 1: • Impact on the bacterial microbiome of anti-staphylococcal phage gel and systemically chosen antibiotics.
Time frame: 7 months
Work Package 2: Safety of phage gel and overt toxic effect of phage gel.
Time frame: 7 months
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.
Time frame: 16 months
Work Package 2: Impact on the bacterial microbiome of systemically chosen antibiotics and of anti-staphylococcal phage gel.
Time frame: 16 months
Work Package 3: Safety of phage gel and overt toxic effect of phage gel.
Time frame: 16 months
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.
Time frame: 16 months
Work Package 3: Impact on the bacterial microbiome of systemically chosen antibiotics and of anti-staphylococcal phage gel.
Time frame: 16 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2020.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Phage in people with Diabetes and Diabetic Foot, run by University Hospitals of Derby and Burton NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 28 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: 7 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2020; AzTrials last refreshed its copy on 8 Nov 2026.