Abbreviated Protocol for Two-Stage Exchange

NCT ID: NCT04662632

Last Updated: 2024-04-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 76 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-01
• Study Completion Date: 2023-12-22

Brief 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.

Conditions

Prosthetic Joint Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

VT-X7 Treatment System with Tobramycin Sulfate

Intervention Type: COMBINATION_PRODUCT

Seven-day local antibiotic irrigation with tobramycin sulfate via the VT-X7 Knee or Hip Spacer.

Two-stage exchange arthroplasty

Intervention Type: PROCEDURE

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 Hydrochloride

Intervention Type: COMBINATION_PRODUCT

Seven-day local antibiotic irrigation with vancomycin hydrochloride via the VT-X7 Knee or Hip Spacer.

Control

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.

Group Type: ACTIVE_COMPARATOR

Standard of Care

Intervention Type: DRUG

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 arthroplasty

Intervention Type: PROCEDURE

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).

Interventions

VT-X7 Treatment System with Tobramycin Sulfate

Seven-day local antibiotic irrigation with tobramycin sulfate via the VT-X7 Knee or Hip Spacer.

Intervention Type: COMBINATION_PRODUCT

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.

Intervention Type: DRUG

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).

Intervention Type: PROCEDURE

VT-X7 Treatment System with Vancomycin Hydrochloride

Seven-day local antibiotic irrigation with vancomycin hydrochloride via the VT-X7 Knee or Hip Spacer.

Intervention Type: COMBINATION_PRODUCT

Eligibility Criteria

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)

• Minimum Eligible Age: 22 Years
• Maximum Eligible Age: 84 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Osteal Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bryan Springer, MD

Role: PRINCIPAL_INVESTIGATOR

Ortho Carolina

Locations

University of Arizona, Phoenix

Phoenix, Arizona, United States

Harbor-UCLA Medical Center

Torrance, California, United States

VA Medical Center

Washington D.C., District of Columbia, United States

University of Florida

Gainesville, Florida, United States

Cleveland Clinic

Weston, Florida, United States

University of Kentucky

Lexington, Kentucky, United States

Covenant Medical Center

Saginaw, Michigan, United States

New York University

New York, New York, United States

Columbia

New York, New York, United States

OrthoCarolina Research Institute, Inc

Charlotte, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

Ohio State University

Columbus, Ohio, United States

Integris Southwest Medical Center

Oklahoma City, Oklahoma, United States

Rothman Orthopaedic Institute

Philadelphia, Pennsylvania, United States

Texas Health Presbyterian

Plano, Texas, United States

University of Utah

Salt Lake City, Utah, United States

UVA Orthopedics Center

Charlottesville, Virginia, United States

Countries

United States

Other Identifiers

JPS-0301

Identifier Type: -

Identifier Source: org_study_id