Abbreviated Protocol for Two-Stage Exchange

Prosthetic Joint Infection Clinical Trial

— APEX  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04662632
• Other study ID #: JPS-0301
• Status: Completed
• Phase: Phase 2
• Start date: November 1, 2021
• Est. completion date: December 22, 2023

Study information

• Verified date: March 2024
• Source: Osteal Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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). 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: December 22, 2023
• Est. primary completion date: March 13, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 22 Years to 84 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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;

• 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)

Related Conditions & MeSH terms

• Infections
• Prosthetic Joint Infection

Intervention

Combination Product:
• VT-X7 Treatment System with Tobramycin Sulfate
Seven-day local antibiotic irrigation with tobramycin sulfate via the VT-X7 Knee or Hip Spacer.

Drug:
• Standard of Care
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.

Procedure:
• Two-stage exchange arthroplasty
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).

Combination Product:
• VT-X7 Treatment System with Vancomycin Hydrochloride
Seven-day local antibiotic irrigation with vancomycin hydrochloride via the VT-X7 Knee or Hip Spacer.

Locations

Country	Name	City	State
United States	OrthoCarolina Research Institute, Inc	Charlotte	North Carolina
United States	UVA Orthopedics Center	Charlottesville	Virginia
United States	Cleveland Clinic	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	University of Florida	Gainesville	Florida
United States	University of Kentucky	Lexington	Kentucky
United States	Columbia	New York	New York
United States	New York University	New York	New York
United States	Integris Southwest Medical Center	Oklahoma City	Oklahoma
United States	Rothman Orthopaedic Institute	Philadelphia	Pennsylvania
United States	University of Arizona, Phoenix	Phoenix	Arizona
United States	Texas Health Presbyterian	Plano	Texas
United States	Covenant Medical Center	Saginaw	Michigan
United States	University of Utah	Salt Lake City	Utah
United States	Harbor-UCLA Medical Center	Torrance	California
United States	VA Medical Center	Washington	District of Columbia
United States	Cleveland Clinic	Weston	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Osteal Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	90 days
Secondary	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.	180 days
Secondary	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.	365 days