"Debridement PhagE AnTibiotics for PJI"

NCT07698002 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: DePHEAT PJI
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Total joint replacement (TJR) has revolutionized care provided for patients suffering from disabling joint pain. Unfortunately, periprosthetic joint infection (PJI) remains a devastating complication and the leading cause of failure after TJR. Current standard treatment for PJI requires multiple surgical revisions of the infected prosthesis in combination with a prolonged course of systemic antibiotic therapy. Debridement Antibiotic and Implant Retention (DAIR) procedure is one of the surgical options that is routinely used to manage PJI, due to its lower risk of morbidity and surgical cost. DAIR is often used for patients who present with an acute PJI or who cannot tolerate a complex implant revision. However, the overall success rate for DAIR is ranging between 60-70%. DAIR failures are often attributed to the residual infection and biofilm burden left behind on the retained implant surface, which cannot be targeted effectively with post-operative systemic antibiotics. Therefore, research has been ongoing to identify non-surgical multidrug resistance (MDR) treatment adjuncts that can synergize the therapeutic effects of antibiotics in PJI care. Numerous preclinical bone and joint infection models have clearly demonstrated such therapeutic benefits using bacteriophages (phages). Phages target bacterial cells and breakdown biofilm that it forms on the implant surface. Each bacterial strain tends to have a particular phage that is susceptible to that bacterial strain. Due to this phage specificity and the fact that bacteria can still develop resistance against a single phage, the concept of using a phage cocktail (mixture of 2 or more phage candidates) has been the preferred treatment approach for applying phage therapy. Using a phage cocktail provides a broader spectrum of bacterial strain coverage and makes it harder for the bacteria to develop resistance. Published literature has considered phage therapy to be safe for direct administration at the infection site with minimal adverse events provided that the phage preparation administered meets Good Manufacturing Practice (GMP). The DePHEAT PJI trail, is a prospective, single center, 1:1 non-blinded feasibility randomized controlled trial (RCT) that aims to assess the safety and the effectiveness of the experimental phage therapy cocktails for patients with hip or knee PJI caused by either Staphylococcus (S.) aureus or Pseudomonas (P.) aeruginosa and comparing it to standardized therapy. The investigator hypothesizes that this pilot RCT will help evaluate the practicality and potential risks associated with adding phage therapy to the conventional standard of care treatment plan. This will initiate the development of a necessary infrastructure for future phage trials and programs that expand our understanding on the benefits of using phage therapy for acute PJI.

Conditions

Periprosthetic Infection

Keywords

Phage therapy; Periprosthetic Joint Infection; Bacteriophage

Outcome Measures

Primary Outcomes (2)

• Incidence of treatment emergent adverse event

  focuses on documenting any adverse events (both transient and persistent) or reactions associated with phage therapy. * Monitoring for signs and symptoms of allergic reactions after each phage administration, which could be manifested as fever, rash, flushing, hypotension * Monitoring for any signs and symptoms of emerging new infections * Monitoring for emergence of resistance to phage therapy or to antibiotics

  up to 12 months

• Evaluation of the feasibility of the trial design

  To assess the practical aspect of administering phage therapy in a hospital setting. This trial will define the achievability of performing a future larger scale trial. This trial will be evaluating the following: * logistical challenges related to transportation, storage and handling of phage therapy * operational challenges including technical and time feasibility factors * patient recruitment and acceptance to participating in such a trial

  up to 3 months

Secondary Outcomes (3)

• Assessment of clinical response effectiveness to phage therapy

  up to 12 months

• Assessment of Microbiological effectiveness of phage therapy

  up to 12 months

• Assessment of biochemical effectiveness of the phage therapy

  Up to 12 months

Study Arms (2)

Standard of care (DAIR + Antibiotics)

NO INTERVENTION

Patients will receive the standard of care for hip and knee periprosthetic joint infection which is DAIR ( Debridement Antibiotic and Implant Retention) and antibiotic according to the bacterial culture.

Bacteriophage treatment + DAIR + Antibiotics

EXPERIMENTAL

In addition to the standard of care procedure (DAIR and antibiotics), patients in the experimental arm will receive 3 doses of intra-articular phage therapy. The first dose will be given intra-operatively after the DAIR and then will be done at day 14 and day 21 postoperatively. The second and third intra-articular injections will be done under image guidance.

Biological: The investigational product specifically targeting P. aeruginosa (DP-QB-PSA-005) and that targeting S. aureus (DP-QB-STA-005), each formed of a mixture of 5 bacteriophages.

Interventions

The investigational product specifically targeting P. aeruginosa (DP-QB-PSA-005) and that targeting S. aureus (DP-QB-STA-005), each formed of a mixture of 5 bacteriophages. BIOLOGICAL

For participants randomized to the intervention arm will receive a total of 3 local administrations (intra-articular) of the appropriate phage cocktail to the infected joint. The first dose will be administered intraoperatively during the DAIR procedure after closing the joint capsule. The second dose will be administered on post-operative days (POD) 14 and the third dose will be administered POD 21. The second and third doses will be administered by interventional radiology using image guidance (fluoroscopy) as per standard drug administration.

Also known as: Bacteriophage therapy

Bacteriophage treatment + DAIR + Antibiotics

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients are 18 years or older
• Patients have been diagnosed with bacterial PJI caused by a single organism (either S. aureus or P. aeruginosa) confirmed through synovial fluid cultures.
• Patients are undergoing DAIR surgical procedure for hip or knee PJI
• Patients are clinically stable and independently mobile
• Patients are willing and able to consent

You may not qualify if:

• Patients have cultured multiple bacteria, and it is difficult for physicians to determine which bacteria is causing the disease
• Patients develop a life-threatening condition or a condition that leads to deterioration of the patient's medical condition and that is unrelated to the known PJI as cerebrovascular accident, angina, cancer.
• Patient's clinical condition is no longer stable and deteriorating, for example, if the patient develops sepsis secondary to PJI prior to the commencement of the phage therapy.
• Patients who have only been through a hemiarthroplasty or uni-compartmental arthroplasty with infected implant component
• Patients receiving any immunomodulating or immunosuppressive therapy medications for malignancy or autoimmune disease (with exception to inflammatory arthritis), chronic glucocorticoid use (≥ 20mg of prednisolone daily for at least 1 month with another cause of immunosuppression), and history of solid organ and/or bone marrow transplantation.
• Presence of concurrent active viral infection, or history of uncontrolled HIV (CD4 count \<200 cells/uL).
• Patient is pregnant or breast feeding

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead

Study Sites (1)

Ottawa Hospital Research Institute

Ottawa, Canada

Location

MeSH Terms

Interventions

Phage Therapy

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Hesham Abdelbary, MD MSc FRCSC

  The Ottawa Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a pilot 1:1 non blinded randomized controlled trial.

Study Record Dates

• First Submitted: June 15, 2026
• First Posted: July 13, 2026
• Study Start: July 2, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2028
• Last Updated: July 13, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)