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Trial record 43 of 109 for:    Recruiting, Not yet recruiting, Available Studies | "Diabetic Foot"

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

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ClinicalTrials.gov Identifier: NCT02664740
Recruitment Status : Not yet recruiting
First Posted : January 27, 2016
Last Update Posted : April 19, 2018
Sponsor:
Collaborator:
Pherecydes Pharma
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Nīmes

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Diabetic Foot Staphylococcal Infections Drug: Topical anti-Staphylococcus bacteriophage therapy Drug: Topical placebo corresponding to anti-Staphylococcus bacteriophage therapy Phase 1 Phase 2

Detailed 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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Comparison of the Efficacy of Standard Treatment Associated With Phage Therapy Versus Standard Treatment Plus Placebo for Diabetic Foot Ulcers Monoinfected by Staphylococcus Aureus: a Randomized, Multi-centre, Controlled, 2-parallel-group, Double-blind, Superiority Trial
Estimated Study Start Date : January 2019
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : August 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Phage therapy

Patients randomized to this arm will have phage therapy.

Intervention: Topical anti-Staphylococcus bacteriophage therapy

Drug: Topical anti-Staphylococcus bacteriophage therapy
Patients randomized to the experimental arm will receive sterile compress dressings impregnated with a phage solution of 10^7 PFU/ml on days 0, 7 and 14 (unless the wound is already healed, i.e. phage solutions are not applied to healed wounds).

Placebo Comparator: Placebo

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

Drug: Topical placebo corresponding to anti-Staphylococcus bacteriophage therapy
Patients randomized to the placebo arm will receive sterile compress dressings impregnated with a placebo solution on days 0, 7 and 14 (unless the wound is already healed, i.e. placebo solutions are not applied to healed wounds).




Primary Outcome Measures :
  1. The relative reduction in wound surface area (%) [ Time Frame: 12 weeks ]

Secondary Outcome Measures :
  1. Immediate Safety [ Time Frame: Day 0, 1 hour after application of experimental dressing ]
    The presence/absence of the following symptoms during each 1 hour observation periods following the application of each experimental wound dressing: local side effects (local rash onset or worsening of local inflammatory signs) and general symptoms (vital signs, fever, rash, arthralgia, gastro-intestinal symptoms...) will be performed.

  2. Immediate Safety [ Time Frame: Day 7, 1 hour after application of experimental dressing ]
    The presence/absence of the following symptoms during each 1 hour observation periods following the application of each experimental wound dressing: local side effects (local rash onset or worsening of local inflammatory signs) and general symptoms (vital signs, fever, rash, arthralgia, gastro-intestinal symptoms...) will be performed.

  3. Immediate Safety [ Time Frame: Day 14, 1 hour after application of experimental dressing ]
    The presence/absence of the following symptoms during each 1 hour observation periods following the application of each experimental wound dressing: local side effects (local rash onset or worsening of local inflammatory signs) and general symptoms (vital signs, fever, rash, arthralgia, gastro-intestinal symptoms...) will be performed.

  4. The number of MedDRA coded Adverse Events per patient [ Time Frame: throughout the study; 12 weeks ]
  5. The presence/absence of abnormal laboratory results [ Time Frame: throughout the study; 12 weeks ]
  6. Wound surface area [ Time Frame: 2 weeks ]
  7. Wound surface area [ Time Frame: 4 weeks ]
  8. Wound surface area [ Time Frame: 6 weeks ]
  9. Wound surface area [ Time Frame: 8 weeks ]
  10. Wound surface area [ Time Frame: 10 weeks ]
  11. Wound surface area [ Time Frame: 12 weeks ]
  12. Wound depth [ Time Frame: 2 weeks ]
  13. Wound depth [ Time Frame: 4 weeks ]
  14. Wound depth [ Time Frame: 6 weeks ]
  15. Wound depth [ Time Frame: 8 weeks ]
  16. Wound depth [ Time Frame: 10 weeks ]
  17. Wound depth [ Time Frame: 12 weeks ]
  18. Time to healing [ Time Frame: censored at 12 weeks ]
  19. The % of completely healed wounds [ Time Frame: 12 weeks ]
  20. Classification of Staphylococcus isolates as MSSA or MRSA resistant [ Time Frame: 4 weeks ]

    MSSA: Methicillin-susceptible Staphylococcus aureus MRSA: Methicillin-resistant Staphylococcus aureus

    What is reported is a binary result: isolates are classified as either "MSSA" or "MRSA"


  21. Classification of Staphylococcus isolates as MSSA or MRSA resistant [ Time Frame: at modification of the first-line treatment or new antibiotic prescription (if any; most likey at 14 days and before 12 weeks) ]

    MSSA: Methicillin-susceptible Staphylococcus aureus MRSA: Methicillin-resistant Staphylococcus aureus

    What is reported is a binary result: isolates are classified as either "MSSA" or "MRSA"


  22. Classification of Staphylococcus isolates as MSSA or MRSA resistant [ Time Frame: at week 12 if the wound is still not healed ]

    MSSA: Methicillin-susceptible Staphylococcus aureus MRSA: Methicillin-resistant Staphylococcus aureus

    What is reported is a binary result: isolates are classified as either "MSSA" or "MRSA"


  23. Classification of Staphylococcus isolates according to clonal complexes (virulence classification) [ Time Frame: 4 weeks ]
  24. Classification of Staphylococcus isolates according to clonal complexes (virulence classification) [ Time Frame: at modification of the first-line treatment or new antibiotic prescription (if any; most likey at 14 days and before 12 weeks) ]
  25. Classification of Staphylococcus isolates according to clonal complexes (virulence classification) [ Time Frame: at week 12 if the wound is still not healed ]
  26. Presence/absence of non-Staphylococcus aureus bacteria that are antibiotic-resistant [ Time Frame: week 0 ]
  27. Presence/absence of non-Staphylococcus aureus bacteria that are antibiotic-resistant [ Time Frame: week 4 ]
  28. Presence/absence of non-Staphylococcus aureus bacteria that are antibiotic-resistant [ Time Frame: at modification of the first-line treatment or new antibiotic prescription (if any; most likey at 14 days and before 12 weeks) ]
  29. Presence/absence of non-Staphylococcus aureus bacteria that are antibiotic-resistant [ Time Frame: at week 12 if the wound is still not healed ]
  30. Wound microbiota: OTU richness [ Time Frame: week 0 ]
    OTU: Operational Taxonomic Unit

  31. Wound microbiota: OTU richness [ Time Frame: week 4 ]
    OTU: Operational Taxonomic Unit

  32. Wound microbiota: OTU richness [ Time Frame: at modification of the first-line treatment or new antibiotic prescription (if any; most likey at 14 days and before 12 weeks) ]
    OTU: Operational Taxonomic Unit

  33. Wound microbiota: OTU richness [ Time Frame: at week 12 if the wound is still not healed ]
    OTU: Operational Taxonomic Unit

  34. Wound microbiota: Shannon's Diversity [ Time Frame: week 0 ]
  35. Wound microbiota: Shannon's Diversity [ Time Frame: week 4 ]
  36. Wound microbiota: Shannon's Diversity [ Time Frame: at modification of the first-line treatment or new antibiotic prescription (if any; most likey at 14 days and before 12 weeks) ]
  37. Wound microbiota: Shannon's Diversity [ Time Frame: at week 12 if the wound is still not healed ]
  38. Wound microbiota: Functional richness [ Time Frame: week 0 ]
  39. Wound microbiota: Functional richness [ Time Frame: week 4 ]
  40. Wound microbiota: Functional richness [ Time Frame: at modification of the first-line treatment or new antibiotic prescription (if any; most likey at 14 days and before 12 weeks) ]
  41. Wound microbiota: Functional richness [ Time Frame: at week 12 if the wound is still not healed ]
  42. Wound microbiota: Functional diversity [ Time Frame: week 0 ]
  43. Wound microbiota: Functional diversity [ Time Frame: week 4 ]
  44. Wound microbiota: Functional diversity [ Time Frame: at modification of the first-line treatment or new antibiotic prescription (if any; most likey at 14 days and before 12 weeks) ]
  45. Wound microbiota: Functional diversity [ Time Frame: at week 12 if the wound is still not healed ]
  46. Wound microbiota: the relative abundance of Staphylococcus relative to other bacteria in the wound [ Time Frame: week 0 ]
  47. Wound microbiota: the relative abundance of Staphylococcus relative to other bacteria in the wound [ Time Frame: week 4 ]
  48. Wound microbiota: the relative abundance of Staphylococcus relative to other bacteria in the wound [ Time Frame: at modification of the first-line treatment or new antibiotic prescription (if any; most likey at 14 days and before 12 weeks) ]
  49. Wound microbiota: the relative abundance of Staphylococcus relative to other bacteria in the wound [ Time Frame: at week 12 if the wound is still not healed ]
  50. Wound microbiota: the number of Staphylococcus strains in a wound [ Time Frame: week 0 ]
  51. Wound microbiota: the number of Staphylococcus strains in a wound [ Time Frame: week 4 ]
  52. Wound microbiota: the number of Staphylococcus strains in a wound [ Time Frame: at modification of the first-line treatment or new antibiotic prescription (if any; most likey at 14 days and before 12 weeks) ]
  53. Wound microbiota: the number of Staphylococcus strains in a wound [ Time Frame: at week 12 if the wound is still not healed ]
  54. Wound microbiota: the relative abundance of Staphylococcus aureus relative to other bacteria in the wound [ Time Frame: week 0 ]
  55. Wound microbiota: the relative abundance of Staphylococcus aureus relative to other bacteria in the wound [ Time Frame: week 4 ]
  56. Wound microbiota: the relative abundance of Staphylococcus aureus relative to other bacteria in the wound [ Time Frame: at modification of the first-line treatment or new antibiotic prescription (if any; most likey at 14 days and before 12 weeks) ]
  57. Wound microbiota: the relative abundance of Staphylococcus aureus relative to other bacteria in the wound [ Time Frame: at week 12 if the wound is still not healed ]
  58. Wound microbiota: the relative abundance of Staphylococcus aureus relative to other Staphylococcus in the wound [ Time Frame: week 0 ]
  59. Wound microbiota: the relative abundance of Staphylococcus aureus relative to other Staphylococcus in the wound [ Time Frame: week 4 ]
  60. Wound microbiota: the relative abundance of Staphylococcus aureus relative to other Staphylococcus in the wound [ Time Frame: at modification of the first-line treatment or new antibiotic prescription (if any; most likey at 14 days and before 12 weeks) ]
  61. Wound microbiota: the relative abundance of Staphylococcus aureus relative to other Staphylococcus in the wound [ Time Frame: at week 12 if the wound is still not healed ]
  62. Wound microbiota: ordination scores on each of two principal components extracted from UniFrac distances between all bacterial samples taken during the study [ Time Frame: week 0 ]
  63. Wound microbiota: ordination scores on each of two principal components extracted from UniFrac distances between all bacterial samples taken during the study [ Time Frame: week 4 ]
  64. Wound microbiota: ordination scores on each of two principal components extracted from UniFrac distances between all bacterial samples taken during the study [ Time Frame: at modification of the first-line treatment or new antibiotic prescription (if any; most likey at 14 days and before 12 weeks) ]
  65. Wound microbiota: ordination scores on each of two principal components extracted from UniFrac distances between all bacterial samples taken during the study [ Time Frame: at week 12 if the wound is still not healed ]
  66. The presence/absence of anti-phage antibodies in plasma samples [ Time Frame: week 0 ]
  67. The presence/absence of anti-phage antibodies in plasma samples [ Time Frame: week 4 ]
  68. The presence/absence of anti-phage antibodies in plasma samples [ Time Frame: at modification of the first-line treatment or new antibiotic prescription (if any; most likey at 14 days and before 12 weeks) ]
  69. The presence/absence of anti-phage antibodies in plasma samples [ Time Frame: at week 12 if the wound is still not healed ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 target wound is classified as P (1 or 2), E (1-30 cm^2), D (2), I (2) and S (1 or 2) according to the PEDIS classification

Participant final 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 target wound is classified as P (1 or 2), E (1-30 cm^2), D (2), I (2) and S (1 or 2) according to the PEDIS classification
  • The patient's wound is mono-infected with Staphylococcus aureus (MRSA or MSSA)

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

Participant final 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 who have received antibiotics within the 7 days preceding inclusion
  • Patients with diabetic foot wounds associated with clinical or radiographic signs of arthritis or osteomyelitis*
  • Patients with diabetic foot wounds associated with critical limb ischemia according to P = grade 3 in the PEDIS classification
  • Patients whose wound is infected by a pathogen other than S. aureus (includes multi-infections) according to bacteriological sampling performed at the pre-inclusion visit

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02664740


Contacts
Contact: Albert Sotto, MD, PhD +33.(0)6.09.56.66.55 albert.sotto@chu-nimes.fr
Contact: Carey Suehs, PhD +33.(0)4.66.68.67.88 carey.suehs@chu-nimes.fr

Locations
France
CHU de Bordeaux - Hôpital Pellegrin Not yet recruiting
Bordeaux, France, 33000
Principal Investigator: Michel Dupon, MD, PhD         
CHRU de Nîmes - Hôpital Universitaire de Réadaptation du Grau du Roi Not yet recruiting
Le Grau du Roi, France, 30240
Principal Investigator: Sophie Schuldiner, MD         
CHU de Nantes - Hôtel Dieu Not yet recruiting
Nantes Cedex 1, France, 44093
Principal Investigator: David Boutoille, MD, PhD         
APHP - Groupe Hospitalier Pitié-Salpetrière Not yet recruiting
Paris Cedex 13, France, 75651
Principal Investigator: Agnès Hartemann, MD, PhD         
APHP - Hôpital Lariboisière Not yet recruiting
Paris, France, 75010
Principal Investigator: Jean-François Gautier, MD,PhD         
CHRU de Toulouse - Hôpital de Rangueil Not yet recruiting
Toulouse Cedex 9, France, 31059
Principal Investigator: Jacques Martini, MD         
CH de Tourcoing Not yet recruiting
Tourcoing, France, 59200
Principal Investigator: Eric Senneville, MD, PhD         
Institut Robert Merle d'Aubigné Not yet recruiting
Valenton, France, 94460
Principal Investigator: Gérard Chiesa, MD         
CH Intercommunal de Villeneuve-Saint-Georges Not yet recruiting
Villeneuve-Saint-Georges, France, 94195
Principal Investigator: Olivier Patey, MD         
Sponsors and Collaborators
Centre Hospitalier Universitaire de Nīmes
Pherecydes Pharma
Investigators
Study Director: Albert Sotto, MD, PhD Centre Hospitalier Universitaire de Nîmes

Responsible Party: Centre Hospitalier Universitaire de Nīmes
ClinicalTrials.gov Identifier: NCT02664740     History of Changes
Other Study ID Numbers: PHRC-N/2015/AS-01
First Posted: January 27, 2016    Key Record Dates
Last Update Posted: April 19, 2018
Last Verified: April 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Centre Hospitalier Universitaire de Nīmes:
Phage Therapy

Additional relevant MeSH terms:
Diabetic Foot
Foot Ulcer
Staphylococcal Infections
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Leg Ulcer
Skin Ulcer
Skin Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Diabetic Neuropathies
Foot Diseases
Gram-Positive Bacterial Infections
Bacterial Infections