Standard Treatment Associated With Phage Therapy Versus Placebo for Diabetic Foot Ulcers Infected by S. Aureus (PhagoPied)

Centre Hospitalier Universitaire de Nīmes

Status and phase: Begins enrollment in 5 months; Phase 2; Phase 1

Conditions: Staphylococcal Infections; Diabetic Foot

Treatments: Drug: Topical anti-Staphylococcus bacteriophage therapy; Drug: Topical placebo corresponding to anti-Staphylococcus bacteriophage therapy

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02664740

PHRC-N/2015/AS-01

Details and patient eligibility

About

The primary objective of this study is to compare the efficacy of standard treatment associated with a topical anti-staphylococcal bacteriophage cocktail versus standard treatment plus placebo for diabetic foot ulcers monoinfected by methicillin-resistant or susceptible S. aureus (MRSA or MSSA) as measured by the relative reduction in wound surface area (%) at 12 weeks.

Full description

The secondary objectives of this study are:

A. To compare the two study arms in terms of treatment safety and tolerance throughout the study.

B. To compare the two study arms in terms of further changes in wound healing at weeks 2, 4, 6, 8, 10, 12.

C. To describe the changes in the resistance and virulence of S. aureus (if present in the wound) from baseline to week 4, at modification of the first-line treatment or new antibiotic prescription (if any) and at week 12 if the wound is still not healed.

D. To describe in the two study arms the antibiotic resistance status of other bacteria isolated from wounds at week 4, at modification of the first-line treatment or new antibiotic prescription (if any) and at week 12 if the wound is still not healed.

E. To describe in the two study arms changes in wound microbiota from baseline to week 4, at modification of the first-line treatment or new antibiotic prescription (if any) and at week 12 if the wound is still not healed.

F. To describe the production of anti-phage antibodies during the topical treatment: baseline and week 4, at modification of the first-line treatment or new antibiotic prescription (if any), and at week 12.

G. Creation of a biobank for future ancillary studies (including, but not limited to, cytokine levels and cellular immune responses): days 0 and week 4, as well as week 12.

Enrollment: 60 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Participant pre-inclusion criteria:

• The patient must have given his/her informed and signed consent

• The patient must be insured or beneficiary of a health insurance plan

• The patient is at least 18 years old

• The patient has type 1 or type 2 diabetes

• The patient is hospitalized/consulting in a participating centre

• The patient has a wound below the ankle that has be evolving for >2 weeks

• The patient has a neuropathic foot wound, classified S (0 or 1), I (0 or 1), N (1), B (1), A (0 or1) and D (1) according to the SINBAD classification,

  • without ischaemia or with non-critical ischaemia defined by: ankle arterial pressure > 50 mm Hg or toe systolic arterial pressure > 30 mm Hg or TcpO2 > 30 mm Hg )
  • with a surface area ≥ 0,5 cm2
  • With IWGDF/IDSA grade 2 or 3 infection without osteomyelitis (normal radiography*)

• Females of childbearing potential or Sexually active males with partner of childbearing potential: commitment to consistently and correctly use an acceptable method of birth control (oral, transdermal, systemic or implant contraception birth control, intrauterine devices) for 1 month after the last study drug administration

• Negative pregnancy test must be obtained before starting any experimental drug

• Females of non-childbearing potential: either surgically sterilized or at least 1 year postmenopausal (amenorrhea duration at least 12 months)

Participant final inclusion criteria:

• The patient has a neuropathic foot wound:

  • Classified S (0 or 1), I (0 or 1), N (1), B (1), A (0 or1) and D (1) according to the SINBAD classification,

• without ischaemia or with non-critical ischaemia defined by: ankle arterial pressure > 50 mm Hg or toe systolic arterial pressure > 30 mm Hg or TcpO2 > 30 mm Hg )

• with a surface area ≥ 0,5 cm2

  • With IWGDF/IDSA grade 2 or 3 infection without osteomyelitis

• The patient's wound is monoinfected by methicillin-resistant or susceptible S. aureus (MSSA or MRSA ), or infected by MSSA or MRSA and other bacteria (a total of 3 bacteria when accounting for MSSA or MRSA)

• The Phagogram of the patient demonstrated that the strains are susceptible to at least one phage(PP1493 and/or PP1815).

Participant pre-exclusion criteria:

• The patient is participating in, or has participated in over the past three months, another trial
• The patient is participating in, or has participated in over the past three months, another study that may interfere with the results or conclusions of this study
• The patient is in an exclusion period determined by a previous study
• The patient is under judicial protection, or is an adult under guardianship
• It is impossible to correctly inform the patient
• The patient refuses to sign the consent
• The patient is pregnant, parturient or breastfeeding. Patients should not be enrolled if they plan to become pregnant during the treatment period and 1 month after the last administration of study drug
• Women/Men refusing to use an effective contraception during and1 month after the last administration of study drug

Participant final exclusion criteria:

• The patient refuses to participate to the study
• The patient is pregnant, parturient or breastfeeding. Patients should not be enrolled if they plan to become pregnant during the treatment period and 1 month after the last administration of study drug
• Women/Men refusing to use an effective contraception during and1 month after the last administration of study drug
• Patients with diabetic foot wounds associated with clinical or radiographic signs of arthritis or osteomyelitis*
• Patient is not infected by S. aureus or infected by more than 3 bacteria even if the culture isolates a S. aureus.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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60 participants in 2 patient groups, including a placebo group

Phage therapy

Experimental group

Description:

Patients randomized to this arm will have phage therapy. Intervention: Topical anti-Staphylococcus bacteriophage therapy

Treatment:

Drug: Topical anti-Staphylococcus bacteriophage therapy

Placebo

Placebo Comparator group

Description:

Patients randomized to this arm will have placebo therapy anologous to that of the experimental arm. Intervention: Topical placebo corresponding to anti-Staphylococcus bacteriophage therapy

Treatment:

Drug: Topical placebo corresponding to anti-Staphylococcus bacteriophage therapy