Prosthetic Joint InfectionPhase 2APEXNCT04662632
Abbreviated Protocol for Two-Stage Exchange
A Phase 2 study testing VT-X7 Treatment System with Tobramycin Sulfate, Two-stage exchange arthroplasty and VT-X7 Treatment System with Vancomycin Hydrochloride in people with Prosthetic Joint Infection, run by Osteal Therapeutics, Inc. at 17 sites in United States.
Trial summary
Study Type: A multi-site, parallel group, randomized trial. Study Objectives: The objective is to evaluate safety and determine preliminary efficacy of VT-X7 (Vancomycin and Tobramycin Exchanged over 7 Days). Read more about this study
- Who is it for?
- Ages 22 to 84 years
- Conditions the study is for
- Prosthetic Joint Infection
- What is being tested?
- VT-X7 Treatment System with Tobramycin Sulfate, Two-stage exchange arthroplasty and VT-X7 Treatment System with Vancomycin Hydrochloride
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 76 participants
- Where
- 17 sitesUnited States
- Study dates
- 1 Nov 2021to 22 Dec 2023
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 22 to 84 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Scheduled for two-stage exchange arthroplasty due to hip or knee PJI
- Signed informed consent
- 22 to 84 years of age (inclusive)
- Medical clearance for surgery
- Preoperative diagnosis of PJI of the hip or knee per the International Consensus Meeting of Musculoskeletal Infection 2018 definition of Periprosthetic Hip and Knee Infection
Who cannot join
- Patients with 2 or more prior one-stage or two-stage exchange arthroplasties of the infected joint;
- Patients with acute PJI, defined as total joint arthroplasty surgery within 4 weeks prior to enrollment (Stage 1) in this study;
- Patients with bacteremia or positive bacterial blood culture in the last 30 days;
- Patients with concurrent PJI of more than one joint;
- Patients with ongoing active infection of an intravenous site;
- Patients who require long-term anticoagulation or antiplatelet therapy, and for whom bridging or withholding therapy is not recommended based on the individual's clinical condition;
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- Patients with advanced renal insufficiency (chronic kidney disease Stage 4 or greater or glomerular filtration rate <30 mL/min);
- Patients on chemotherapy for malignant disease;
- Patients on systemic glucocorticoid therapy (prednisone >10 mg/day or equivalent);
- Patients with immunodeficiency (e.g., splenectomy, sickle cell anemia, Stage 3 human immunodeficiency virus infection, primary immunodeficiency disease, except immunodeficiency due to immunosuppressive therapy).
- Patients who have an allergy to vancomycin hydrochloride or tobramycin sulfate (Note: prior history of red man syndrome is not considered an allergy);
- Patients who have an allergy to titanium, titanium alloys, polymethylmethacrylate or polyurethane.
- Patients who are pregnant or planning to become pregnant in the next 12 months;
- Patients in whom negative pressure wound therapy is contraindicated;
- Patients with a fungal PJI;
- Patients who have a skeletal defect greater than 150 mm in length in the tibia or femur of the infected joint;
- Patients who have a planned surgical procedure within 6 months of enrollment that can impact the conduct of the study;
- Patients who are breastfeeding at the screening visit;
- Patients who are incarcerated or are facing impending incarceration;
- Patients who have been in treatment or referred for treatment for substance abuse within the past year;
- Patients with any medical condition, including schizophrenia or another psychiatric disorder with hallucinations and/or delusions, that would interfere with the interpretation of the study results, the conduct of the study, or patient participation would not be in the best interest of the patient in the opinion of the Study Site Principal Investigator;
- Patients who will participate in another clinical study of an investigational drug or investigational device or have participated in another clinical study of an investigational drug or investigational device within the past 30 days that would interfere with the interpretation of the study results or conduct of the study;
- Patients who are judged by the Investigator to be unsuitable for the study.
- Patients receiving immunosuppressive drug therapy for bone marrow or another transplant;
- Patients currently or previously enrolled in this study;
- Patients who receive therapy including any of the following biologic agents, which will not be withheld for a period beginning at least one dosing cycle (minimum 7 days) prior to Stage 1 surgery and ending at least 14 days following Stage 2 surgery:
- Adalimumab (Humira) Tocilizumab (Actemra) Etanercept (Enbrel) Anakinra (Kineret) Golimumab (Simponi) Secukinumab (Cosentyx) Infliximab (Remicade) Ustekinumab (Stelara) Abatacept (Orencia) Rituximab (Rituxan) Certolizumab (Cimzia) Tofacitinib (Xeljanz) Belimumab (Benlysta)
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
United States17 sites
OrthoCarolina Research Institute, Inc
Charlotte, North Carolina, 28207
UVA Orthopedics Center
Charlottesville, Virginia, 22903
Cleveland Clinic
Cleveland, Ohio, 44195
Ohio State University
Columbus, Ohio, 43202
University of Florida
Gainesville, Florida, 32611
University of Kentucky
Lexington, Kentucky, 40506
New York University
New York, New York, 10003
Columbia
New York, New York, 10032
Integris Southwest Medical Center
Oklahoma City, Oklahoma, 73103
Rothman Orthopaedic Institute
Philadelphia, Pennsylvania, 19107
University of Arizona, Phoenix
Phoenix, Arizona, 85004
Texas Health Presbyterian
Plano, Texas, 75093
Covenant Medical Center
Saginaw, Michigan, 48602
University of Utah
Salt Lake City, Utah, 84108
Harbor-UCLA Medical Center
Torrance, California, 90502
VA Medical Center
Washington D.C., District of Columbia, 20422
Cleveland Clinic
Weston, Florida, 33331
About this study
Official title: A Randomized Controlled Trial of Alternating Irrigation of Vancomycin Hydrochloride and Tobramycin Sulfate in Patients Undergoing Two-Stage Exchange Arthroplasty for Periprosthetic Joint Infection (PJI) of the Hip or Knee
Study Type: A multi-site, parallel group, randomized trial.
Study Objectives: The objective is to evaluate safety and determine preliminary efficacy of VT-X7 (Vancomycin and Tobramycin Exchanged over 7 Days). Efficacy is evaluated as superiority of the Experimental Arm in a composite endpoint of Overall Success at 90 days, consisting of a revision prosthesis implanted at Stage 2, patient survival, absence of reoperation and absence of periprosthetic joint infection (PJI). Secondary objectives are to evaluate superiority at 365 days in a composite endpoint of Overall Success, and in separate secondary endpoints for quality of life and patient survival. The exploratory objective is to compare Experimental and Control Arms in exploratory endpoints.
Follow-up: Patients will be evaluated at 90-, 180-, and 365-day follow-up visits.
- Conditions
- Prosthetic Joint Infection
- Being tested
- VT-X7 Treatment System with Tobramycin Sulfate, Standard of Care, Two-stage exchange arthroplasty, VT-X7 Treatment System with Vancomycin Hydrochloride
- Keywords
- Hip, Knee, Biofilm, Minimum-biofilm-eradication-concentration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VT-X7 Treatment System with Tobramycin SulfateCombination product
Seven-day local antibiotic irrigation with tobramycin sulfate via the VT-X7 Knee or Hip Spacer.
Standard of CareDrug
Forty-two days (minimum) systemic antibiotic administration adjuvant to two-stage exchange arthroplasty with temporary antibiotic-impregnated cement spacer per standard of care. Antibiotics will be selected by treatment provider and administered in accordance with national and local treatment guidelines.
Two-stage exchange arthroplastyProcedure or surgery
Stage 1 consists of surgical removal of the infected prosthesis, debridement, and implantation of a temporary spacer. Stage 2 surgery consists of explantation of the temporary spacer, debridement, and implantation of a permanent prosthesis, followed by systemic administration of postoperative antibiotics for 42 days (inclusive) to 90 days (inclusive).
VT-X7 Treatment System with Vancomycin HydrochlorideCombination product
Seven-day local antibiotic irrigation with vancomycin hydrochloride via the VT-X7 Knee or Hip Spacer.
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | Local antibiotic irrigation via the VT-X7 (Vancomycin and Tobramycin Exchanged over 7 Days) Treatment System adjuvant to two-stage exchange arthroplasty per standard of care. Receives: Combination Product: VT-X7 Treatment System with Tobramycin Sulfate; Procedure: Two-stage exchange arthroplasty; Combination Product: VT-X7 Treatment System with Vancomycin Hydrochloride |
| Control | Active comparator | Standard of care for treatment of chronic PJI - two-stage exchange arthroplasty: surgical removal of the infected implant, aggressive debridement, and exchange arthroplasty with administration of adjuvant systemic antibiotics and temporary antibiotic-impregnated cement spacer. Receives: Drug: Standard of Care; Procedure: Two-stage exchange arthroplasty |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite Endpoint of Overall Success at 90 Days
Composite endpoint of Overall Success at 90 days consisting of:
- Stage 2 revision prosthesis implanted;
- Absence of PJI* post-Stage 2;
- Absence of reoperation*** of the affected joint pre- or post- Stage 2; and
- Absence of mortality.
- If clinical evidence of infection is present post-Stage 2 surgery, use the International Consensus Meeting on Musculoskeletal Infection 2018 guidelines for definitive PJI confirmation.
- Reoperation includes only procedures to irrigate, debride, and remove or replace the Stage 1 spacer or any Stage 2 implant component.
Measured: 90 days
Secondary outcomes (2)
Composite Endpoint of Overall Success at 180 Days
Composite endpoint of Overall Success at 180 days consisting of:
- Stage 2 revision prosthesis implanted;
- Absence of PJI* post-Stage 2;
- Absence of continued antibiotic therapy for treatment or prophylaxis of PJI **;
- Absence of reoperation*** of the affected joint pre- and post-Stage 2; and
- Absence of mortality.
- If clinical evidence of infection is present post-Stage 2 surgery, use International Consensus Meeting on Musculoskeletal Infection 2018 guidelines for definitive PJI confirmation.
- Continued antibiotic therapy includes antibiotic therapy at 180 days or beyond 12 weeks post-Stage 2 surgery, excluding antibiotics for documented pre-procedural prophylaxis or infection other than PJI.
- Reoperation includes only procedures to irrigate, debride, remove or replace the Stage 1 spacer or any Stage 2 implant component.
Measured: 180 days
Composite Endpoint of Overall Success at 365 Days Consisting of:
Composite endpoint of Overall Success at 365 days consisting of:
- Stage 2 revision prosthesis implanted;
- Absence of PJI* post-Stage 2;
- Absence of continued antibiotic therapy for treatment or prophylaxis of PJI **;
- Absence of reoperation*** of the affected joint pre- and post-Stage 2; and
- Absence of mortality.
- If clinical evidence of infection is present post-Stage 2 surgery, use International Consensus Meeting on Musculoskeletal Infection 2018 guidelines for definitive PJI confirmation.
- Continued antibiotic therapy includes antibiotic therapy at 365 days or beyond 12 weeks post-Stage 2 surgery, excluding antibiotics for documented pre-procedural prophylaxis or infection other than PJI.
- Reoperation includes only procedures to irrigate, debride, remove or replace the Stage 1 spacer or any Stage 2 implant component.
Measured: 365 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2020
- Study start1 Nov 2021
- Primary completion13 Mar 2023
- Study completion22 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Prosthetic Joint InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- Osteal Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bryan Springer, MD, Principal investigator, Ortho Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04662632
- Sponsor's protocol ID
- JPS-0301
- Acronym
- APEX
- Status last verified
- Oct 2026
- First submitted
- 3 Dec 2020
- Last updated
- 15 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Springer BD, Higuera-Rueda CA, de Beaubien BC, Warner KD, Glassman AH, Parvataneni HK, Piuzzi NS. Safety Profile of Seven-Day Intra-articular Antibiotic Irrigation for the Treatment of Chronic Periprosthetic Joint Infection: A Prospective Randomized Phase II Comparative Study. J Arthroplasty. 2024 Sep;39(9 Suppl 1):S229-S235.e1. doi: 10.1016/j.arth.2024.03.069. Epub 2024 Apr 9.
PubMed 38604274