- ICH GCP
- Registr klinických studií v USA
- Klinická studie NCT07619924
Randomized Controlled Study on the Safety and Efficacy of Phage Cocktail in the Treatment of Multidrug-Resistant Bacterial Skin Infections
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.
Přehled studie
Postavení
Typ studie
Zápis (Odhadovaný)
Fáze
- Raná fáze 1
Kontakty a umístění
Studijní místa
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Shaanxi
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Xi'an, Shaanxi, Čína, 710061
- The First Affiliated Hospital of Xi'an Jiaotong University
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dospělý
- Starší dospělý
Přijímá zdravé dobrovolníky
Popis
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.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Čtyřnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Experimentální: Bacteriophage Treatment Group
Receive bacteriophage cocktail therapy for 7 days, combined with antibiotic therapy and conventional treatment.
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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.
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Komparátor placeba: Placebo Group
Receive 0.9% normal saline (placebo) for 7 days, combined with antibiotic therapy and conventional treatment.
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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. |
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Clinical Cure Rate at End of Treatment
Časové okno: From enrollment to the end of the 7-day treatment period.
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Defined as the proportion of patients achieving complete resolution of infection-related clinical symptoms without requiring additional antimicrobial intervention.
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From enrollment to the end of the 7-day treatment period.
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Microbiological Eradication Rate
Časové okno: From enrollment to Day 14 (7 days post-treatment).
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The proportion of patients with eradication (or reduction below the detection limit) of the baseline pathogen, as confirmed by wound culture.
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From enrollment to Day 14 (7 days post-treatment).
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Wound Size Reduction
Časové okno: From enrollment to Day 7, Day 14, and Day 28.
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The relative percentage reduction in wound area from baseline, assessed via standardized measurement.
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From enrollment to Day 7, Day 14, and Day 28.
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Time to Cessation of Exudate
Časové okno: From enrollment through Day 28 follow-up.
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The number of days from treatment initiation until the wound stops producing exudate.
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From enrollment through Day 28 follow-up.
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Incidence of Treatment-Emergent Adverse Events
Časové okno: From enrollment through Day 28 post-treatment.
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Recording of local or systemic adverse events considered related or potentially related to the study treatment.
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From enrollment through Day 28 post-treatment.
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Recurrence/Reinfection Rate within Follow-up
Časové okno: From the end of treatment through the Day 28 follow-up visit.
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The proportion of patients with recurrence or new infection by the same pathogen at the original or adjacent site after initial clinical success.
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From the end of treatment through the Day 28 follow-up visit.
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Patient-reported Pain Score
Časové okno: From enrollment to Day 7, Day 14, and Day 28.
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Change in wound pain intensity as evaluated by the patient using a Visual Analog Scale.
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From enrollment to Day 7, Day 14, and Day 28.
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Spolupracovníci a vyšetřovatelé
Publikace a užitečné odkazy
Obecné publikace
- 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. doi: 10.1093/cid/ciad335.
- GBD 2021 Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance 1990-2021: a systematic analysis with forecasts to 2050. Lancet. 2024 Sep 28;404(10459):1199-1226. doi: 10.1016/S0140-6736(24)01867-1. Epub 2024 Sep 16.
- Schooley RT, Biswas B, Gill JJ, Hernandez-Morales A, Lancaster J, Lessor L, Barr JJ, Reed SL, Rohwer F, Benler S, Segall AM, Taplitz R, Smith DM, Kerr K, Kumaraswamy M, Nizet V, Lin L, McCauley MD, Strathdee SA, Benson CA, Pope RK, Leroux BM, Picel AC, Mateczun AJ, Cilwa KE, Regeimbal JM, Estrella LA, Wolfe DM, Henry MS, Quinones J, Salka S, Bishop-Lilly KA, Young R, Hamilton T. Development and Use of Personalized Bacteriophage-Based Therapeutic Cocktails To Treat a Patient with a Disseminated Resistant Acinetobacter baumannii Infection. Antimicrob Agents Chemother. 2017 Sep 22;61(10):e00954-17. doi: 10.1128/AAC.00954-17. Print 2017 Oct.
- 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.
- Ding X, Tang Q, Xu Z, Xu Y, Zhang H, Zheng D, Wang S, Tan Q, Maitz J, Maitz PK, Yin S, Wang Y, Chen J. Challenges and innovations in treating chronic and acute wound infections: from basic science to clinical practice. Burns Trauma. 2022 May 21;10:tkac014. doi: 10.1093/burnst/tkac014. eCollection 2022.
- 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.
- 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.
- 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 outcomes for 100 consecutive cases: a multicentre, multinational, retrospective observational study. Nat Microbiol. 2024 Jun;9(6):1434-1453. doi: 10.1038/s41564-024-01705-x. Epub 2024 Jun 4.
- 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.
- Sulakvelidze A, Alavidze Z, Morris JG Jr. Bacteriophage therapy. Antimicrob Agents Chemother. 2001 Mar;45(3):649-59. doi: 10.1128/AAC.45.3.649-659.2001. No abstract available.
- Mu A, McDonald D, Jarmusch AK, Martino C, Brennan C, Bryant M, Humphrey GC, Toronczak J, Schwartz T, Nguyen D, Ackermann G, D'Onofrio A, Strathdee SA, Schooley RT, Dorrestein PC, Knight R, Aslam S. Assessment of the microbiome during bacteriophage therapy in combination with systemic antibiotics to treat a case of staphylococcal device infection. Microbiome. 2021 Apr 14;9(1):92. doi: 10.1186/s40168-021-01026-9.
- Chan BK, Stanley GL, Kortright KE, Vill AC, Modak M, Ott IM, Sun Y, Wurstle S, Grun CN, Kazmierczak BI, Rajagopalan G, Harris ZM, Britto CJ, Stewart J, Talwalkar JS, Appell CR, Chaudary N, Jagpal SK, Jain R, Kanu A, Quon BS, Reynolds JM, Teneback CC, Mai QA, Shabanova V, Turner PE, Koff JL. Personalized inhaled bacteriophage therapy for treatment of multidrug-resistant Pseudomonas aeruginosa in cystic fibrosis. Nat Med. 2025 May;31(5):1494-1501. doi: 10.1038/s41591-025-03678-8. Epub 2025 Apr 29.
Užitečné odkazy
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
Další identifikační čísla studie
- 2025YFC3408505
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Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
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