Randomized Controlled Study on the Safety and Efficacy of Phage Cocktail in the Treatment of Multidrug-Resistant Bacterial Skin Infections

Обзор

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.

Вмешательства

• Биопрепарат Bacteriophage 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 bacter
• Препарат Placebo 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 str

Первичные конечные точки

• Clinical Cure Rate at End of Treatment [Срок оценки: From enrollment to the end of the 7-day treatment period.]
• Microbiological Eradication Rate [Срок оценки: From enrollment to Day 14 (7 days post-treatment).]

Вторичные конечные точки (5)

• Wound Size Reduction [Срок оценки: From enrollment to Day 7, Day 14, and Day 28.]
• Time to Cessation of Exudate [Срок оценки: From enrollment through Day 28 follow-up.]
• Incidence of Treatment-Emergent Adverse Events [Срок оценки: From enrollment through Day 28 post-treatment.]
• Recurrence/Reinfection Rate within Follow-up [Срок оценки: From the end of treatment through the Day 28 follow-up visit.]
• Patient-reported Pain Score [Срок оценки: From enrollment to Day 7, Day 14, and Day 28.]

Критерии участия

Критерии включения

• (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.

Критерии исключения

• (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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The First Affiliated Hospital of Xi'an Jiaotong University — Сиань

Публикации

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• Green SI, Clark JR, Santos HH, Weesner KE, Salazar KC, Aslam S, Campbell JW, Doernberg SB, Blodget E, Morris MI, Suh GA, Obeid K, Silveira FP, Filippov AA, Whiteson KL, Trautner BW, Terwilliger AL, Maresso A. A Retrospective, Observational Study of 12 Cases of Expanded-Access Customized Phage Therapy: Production, Characteristics, and Clinical Outcomes. Clin Infect Dis. 2023 Oct 13;77(8):1079-1091. PMID 37279523
• Khatami A, Lin RCY, Petrovic-Fabijan A, Alkalay-Oren S, Almuzam S, Britton PN, Brownstein MJ, Dao Q, Fackler J, Hazan R, Horne B, Nir-Paz R, Iredell JR. Bacterial lysis, autophagy and innate immune responses during adjunctive phage therapy in a child. EMBO Mol Med. 2021 Sep 7;13(9):e13936. doi: 10.15252/emmm.202113936. Epub 2021 Aug 9. PMID 34369652
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• Kohler T, Luscher A, Falconnet L, Resch G, McBride R, Mai QA, Simonin JL, Chanson M, Maco B, Galiotto R, Riat A, Civic N, Docquier M, McCallin S, Chan B, van Delden C. Personalized aerosolised bacteriophage treatment of a chronic lung infection due to multidrug-resistant Pseudomonas aeruginosa. Nat Commun. 2023 Jun 27;14(1):3629. doi: 10.1038/s41467-023-39370-z. PMID 37369702
• Dedrick RM, Freeman KG, Nguyen JA, Bahadirli-Talbott A, Smith BE, Wu AE, Ong AS, Lin CT, Ruppel LC, Parrish NM, Hatfull GF, Cohen KA. Potent antibody-mediated neutralization limits bacteriophage treatment of a pulmonary Mycobacterium abscessus infection. Nat Med. 2021 Aug;27(8):1357-1361. doi: 10.1038/s41591-021-01403-9. Epub 2021 Jul 8. PMID 34239133
• Pirnay JP, Djebara S, Steurs G, Griselain J, Cochez C, De Soir S, Glonti T, Spiessens A, Vanden Berghe E, Green S, Wagemans J, Lood C, Schrevens E, Chanishvili N, Kutateladze M, de Jode M, Ceyssens PJ, Draye JP, Verbeken G, De Vos D, Rose T, Onsea J, Van Nieuwenhuyse B; Bacteriophage Therapy Providers; Bacteriophage Donors; Soentjens P, Lavigne R, Merabishvili M. Personalized bacteriophage therapy PMID 38834776
• Liu M, Hernandez-Morales A, Clark J, Le T, Biswas B, Bishop-Lilly KA, Henry M, Quinones J, Voegtly LJ, Cer RZ, Hamilton T, Schooley RT, Salka S, Young R, Gill JJ. Comparative genomics of Acinetobacter baumannii and therapeutic bacteriophages from a patient undergoing phage therapy. Nat Commun. 2022 Jun 30;13(1):3776. doi: 10.1038/s41467-022-31455-5. PMID 35773283

Идентификаторы

NCT: NCT07619924 · 2025YFC3408505

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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