Bacteriophage Therapy, Phage Therapy, Skin and Soft Tissue Infections
Conditions
Brief summary
This study addresses the increasingly severe global public health challenge of antibiotic resistance, focusing on exploring phage therapy as a potential treatment strategy for multidrug-resistant bacterial skin infections. Bacteriophages, with advantages such as high specificity, low propensity for inducing resistance, and minimal side effects, have shown promise in preliminary clinical research for scenarios like chronic wound infections, demonstrating potential in reducing bacterial load and promoting healing. To this end, the study is designed as a prospective, double-blind, non-inferiority randomized controlled clinical trial, aiming to systematically evaluate the efficacy and safety of phage therapy compared to a placebo or standard treatment in patients with multidrug-resistant bacterial skin infections. The study plans to enroll patients aged 18 to 75 years, clinically diagnosed with a skin infection and with a wound area between 4 and 225 square centimeters. The infection must not involve deep tissue and should be suitable for topical treatment. All enrolled cases must have pathogenic bacteria detected in secretions or wound samples, and these bacteria must be resistant to key antibiotics (such as carbapenems) or show poor response to antibiotic therapy despite \*in vitro\* sensitivity. Patients who have received systemic antibacterial treatment within 72 hours before enrollment with no significant improvement may also be included. Participants of childbearing potential must agree to use effective contraception during the study and voluntarily provide written informed consent. Exclusion criteria primarily include: infections that can be effectively controlled by existing antimicrobials, or pathogens that are insensitive to the phage cocktail used in the study; pregnant or lactating women; patients whose infection symptoms have improved after using antimicrobials within 72 hours before enrollment; those receiving long-term or high-dose corticosteroids, immunosuppressants, chemotherapy, or other treatments that may interfere with the results; participation in other antimicrobial-related clinical trials within the past month; presence of severe wound infections (e.g., necrotizing fasciitis), chronic inflammatory skin diseases, multiple limb ulcers, non-removable implants, or gangrene; anticipated need for amputation surgery; history of clear allergic diseases, immune deficiency (including HIV positivity), mental disorders, or epilepsy; and any other condition deemed by the investigator as unsuitable for participation. These strict inclusion and exclusion criteria aim to select an appropriate target population, ensuring the scientific rigor and credibility of the study results.
Interventions
BIOLOGICALBacteriophage Treatment
Bacteriophage therapy for skin and soft tissue infections typically involves the targeted application of bacteriophage preparations directly to the infected site. Bacteriophage therapy for skin infections involves topical application of phage cocktails to the infected site. These phages specifically target and lyse drug-resistant bacteria, can penetrate biofilms, and are often used alongside standard wound care. Treatment is typically administered daily for 1-2 weeks, focusing on reducing bacterial load and promoting healing with minimal disruption to normal flora.
DRUGPlacebo treatment using 0.9% normal saline
In this double-blind clinical trial, 0.9% normal saline serves as the placebo, designed to be indistinguishable from the active bacteriophage cocktail in formulation, packaging, and appearance. It is administered identically: following standard wound cleaning, a measured volume is applied topically to the wound and covered with the same sterile dressing. The treatment schedule-frequency, duration, and concomitant background care including systemic antibiotics and routine wound management-is strictly standardized across all participants. This ensures any outcome difference is attributable only to the topical agent. Sterile, single-use saline meeting pharmacopeial standards is used to prevent contamination. Blinded researchers assess efficacy and safety at predefined intervals by monitoring wound parameters, bacterial load, and adverse events, maintaining trial integrity for a valid evaluation of the phage therapy's specific effect.
Sponsors
First Affiliated Hospital Xi'an Jiaotong University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* (1) Aged 18 to 75 years, regardless of gender. (2) Clinically diagnosed with a skin infection, with an infected wound area of 4-225 cm². (3) The infection does not involve deep tissues, is suitable for topical treatment, and is not expected to require surgical intervention. (4) Pathogenic bacteria are detected in secretions or wound samples. (5) The pathogen is resistant to key antibiotics (such as carbapenems, etc.), or, despite being susceptible in vitro, shows poor response to antibiotic therapy. (6) Patients who have received systemic antibacterial therapy within 72 hours prior to enrollment without significant improvement may also be included. (7) Subjects of childbearing potential must agree to use effective contraception during the study period. (8) Voluntarily sign the informed consent form, and are willing and able to comply with the requirements of the study protocol.
Exclusion criteria
* (1) The infection can be effectively controlled by available antimicrobial agents, or the causative pathogen is insensitive to the phage cocktail used in this study. (2) Pregnant or breastfeeding women. (3) Patients who have used antimicrobial agents within 72 hours prior to enrollment and have shown improvement in infection symptoms. (4) Patients currently receiving prolonged or high-dose corticosteroids, immunosuppressants, chemotherapy, or other treatments that may interfere with the study results. (5) Patients who have participated in other clinical trials related to antimicrobial agents within the past month. (6) Patients with severe wound infections (e.g., necrotizing fasciitis), chronic inflammatory skin diseases, multiple limb ulcers, non-removable implants, or gangrene, among other conditions. (7) Patients expected to require amputation surgery. (8) Patients with a documented history of allergic disorders, immunodeficiency (including HIV positivity), mental disorders, or epilepsy. (9) Any other condition deemed by the investigator as unsuitable for participation in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Cure Rate at End of Treatment | From enrollment to the end of the 7-day treatment period. | Defined as the proportion of patients achieving complete resolution of infection-related clinical symptoms without requiring additional antimicrobial intervention. |
| Microbiological Eradication Rate | From enrollment to Day 14 (7 days post-treatment). | The proportion of patients with eradication (or reduction below the detection limit) of the baseline pathogen, as confirmed by wound culture. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Wound Size Reduction | From enrollment to Day 7, Day 14, and Day 28. | The relative percentage reduction in wound area from baseline, assessed via standardized measurement. |
| Time to Cessation of Exudate | From enrollment through Day 28 follow-up. | The number of days from treatment initiation until the wound stops producing exudate. |
| Incidence of Treatment-Emergent Adverse Events | From enrollment through Day 28 post-treatment. | Recording of local or systemic adverse events considered related or potentially related to the study treatment. |
| Recurrence/Reinfection Rate within Follow-up | From the end of treatment through the Day 28 follow-up visit. | The proportion of patients with recurrence or new infection by the same pathogen at the original or adjacent site after initial clinical success. |
| Patient-reported Pain Score | From enrollment to Day 7, Day 14, and Day 28. | Change in wound pain intensity as evaluated by the patient using a Visual Analog Scale. |
Countries
China
Outcome results
None listed