Periprosthetic Joint Infection Bubble Study (PJI)

Using Ultrasound and Microbubbles to Augment Antibiotic Efficiency Against Periprosthetic Joint Infections

Patients with an infected knee replacement will receive their standard of care surgical treatment of the infection, with and without additional ultrasound microbubble treatment (randomly divided 50/50 in the active and control groups). Subjects in the active group will receive a local bolus injection of antibiotics and ultrasound-active microbubbles within 24 hours of their revision surgery. The fundamental hypothesis is that a decrease in re-infection rates of at least 24% can be achieved in the active group relative to controls.

Study Overview

• Status: Not yet recruiting
• Conditions: Periprosthetic Joint Infection (PJI)
• Intervention / Treatment: Drug: Ultrasound-triggered microbubble destruction with antibiotics

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center (UPMC)
      • Principal Investigator: Kenneth Urish, MD, PhD
      • Contact: Dana Farrell; Phone Number: 412-641-3156; Email: djf52@pitt.edu
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
      • Contact: Jonathan Thompson; Phone Number: 214-645-1620; Email: jonathan.thompson@utsouthwestern.edu
      • Principal Investigator: Antonia Chen, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Be at least 18 years of age
• Be medically stable
• If female of child-bearing potential, must have a negative pregnancy test
• Be conscious and able to comply with study procedures
• Have read and signed the IRB-approved Informed Consent form for participating in the study
• For Cohort 1, be scheduled for one- or two-stage exchange arthroplasty revision surgery for PJI of the knee
• For Cohort 2, be scheduled for DAIR revision surgery for PJI of the knee

Exclusion Criteria:

• Females who are pregnant or nursing
• Patients currently on chemotherapy requiring systemic treatment
• Patients who are medically unstable, patients who are seriously or terminally ill, and patients whose clinical course is unpredictable
• Patients with a history of anaphylactic allergy to perflutren or any other components of Definity
• Patients with a history of failed one- or two-stage revision for infection
• Patients for which placement of a surgical drain is contraindicated
• Patients in protected classes (e.g., prisoners)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Cohort 1 Exchange anthroplasty; Will be enrolled and randomized into either the treatment or control group. The control group will undergo clinical standard of care with no therapeutic interventions from the study team, only the collection of the wound exudate from the wound drain. The experimental group will undergo an US exam within 24 hours following the revision surgery with a Logiq E10 scanner (GE HealthCare), with a B-mode scan to acquire the radiofrequency (RF) data for the quantitative H-scan analysis, and a contrast-enhanced US (CEUS) scan to perform the UTMD therapy. Following the B-mode scan, the wound site will be sterilized and subjects will receive a localized injection of antibiotics (determined by the orthopaedic surgeon based on intra-operative cultures) and Definity microbubbles to perform the UTMD therapy using commercially-available flash-replenishment sequences.	Drug: Ultrasound-triggered microbubble destruction with antibiotics; A combination of Definity microbubbles and clinically-relevant antibiotics will in injected into the intraarticular space of the knee the day after revision surgery. Ultrasound will be used to rupture the microbubbles to enhance antibiotic activity.; Other Names: antibiotics; ultrasound-triggered microbubble destruction
Other: Cohort 2 Debridement, antibiotics, and implant retention (DAIR) revision surgery; Will be enrolled and randomized into either the treatment or control group. The control group will undergo clinical standard of care with no therapeutic interventions from the study team, only the collection of the wound exudate from the wound drain. The experimental group will undergo an US exam within 24 hours following the revision surgery with a Logiq E10 scanner (GE HealthCare), with a B-mode scan to acquire the radiofrequency (RF) data for the quantitative H-scan analysis, and a contrast-enhanced US (CEUS) scan to perform the UTMD therapy. Following the B-mode scan, the wound site will be sterilized and subjects will receive a localized injection of antibiotics (determined by the orthopaedic surgeon based on intra-operative cultures) and Definity microbubbles to perform the UTMD therapy using commercially-available flash-replenishment sequences.	Drug: Ultrasound-triggered microbubble destruction with antibiotics; A combination of Definity microbubbles and clinically-relevant antibiotics will in injected into the intraarticular space of the knee the day after revision surgery. Ultrasound will be used to rupture the microbubbles to enhance antibiotic activity.; Other Names: antibiotics; ultrasound-triggered microbubble destruction

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Re-Infection Rate	Rate of re-infection within 2 years post-intervention	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Re-Infection	Time between initial intervention and presentation with re-infection	2 years
Bacterial Debris	Measurement of bacterial debris present in would exudate from drains	72 hours

Collaborators and Investigators

• Sponsor: Thomas Jefferson University
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)

Publications and helpful links

General Publications

• Zhao N, Curry D, Evans RE, Isguven S, Freeman T, Eisenbrey JR, Forsberg F, Gilbertie JM, Boorman S, Hilliard R, Dastgheyb SS, Machado P, Stanczak M, Harwood M, Chen AF, Parvizi J, Shapiro IM, Hickok NJ, Schaer TP. Microbubble cavitation restores Staphylococcus aureus antibiotic susceptibility in vitro and in a septic arthritis model. Commun Biol. 2023 Apr 17;6(1):425. doi: 10.1038/s42003-023-04752-y.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2030

Study Registration Dates

• First Submitted: May 14, 2026
• First Submitted That Met QC Criteria: May 14, 2026
• First Posted (Actual): May 20, 2026

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Periprosthetic knee infection; ultrasound-triggered microbubble destruction
• Additional Relevant MeSH Terms: Anti-Infective Agents; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Anti-Bacterial Agents
• Other Study ID Numbers: 2025-0492; 1R01AI187384-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: De-identified data will be shared upon request

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No