A Second Trial of the Abbreviated Protocol Two-Stage Exchange

Phase 2

Completed

Conditions: Prosthetic-joint Infection

Interventions: Combination Product: VT-X7 Treatment System
Procedure: Two-stage exchange arthroplasty
Drug: SOC Antibiotics
Drug: Experimental Antibiotics

Registration Number: NCT05607030

Lead Sponsor: Osteal Therapeutics, Inc.

Brief Summary: Apex-2 is a multi-site, parallel group, randomized trial. Patients will be randomly assigned in a 1:1 ratio to the Experimental Arm or the Control Arm.

The objective of the study is to evaluate safety and determine efficacy of the VT-X7 system. Efficacy is evaluated as superiority of the Experimental Arm in a composite endpoint of Overall Success at 180 days, consisting of a revision prosthesis implanted at Stage 2, absence of periprosthetic joint infection (PJI), absence of continued antibiotic therapy for treatment or prophylaxis of PJI, absence of revision surgery and absence of mortality. Secondary objectives are to evaluate overall success at 365 days, overall safety of the VT-X7 procedure, quality of life (QoL), 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 76

Inclusion Criteria

Scheduled for two-stage exchange arthroplasty due to hip or knee periprosthetic joint infection (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 (ICMMI) 2018 definition of Periprosthetic Hip and Knee Infection

Exclusion Criteria

Patients with 2 or more prior exchange arthroplasties (septic or aseptic) of the infected joint. Exchange of modular components only is not considered an exchange arthroplasty;
Patients with 2 or more prior failed spacers for PJI;
Patients for whom a Stage 2 procedure within one year is contraindicated;
Patients with a medical history or current medical condition that requires a planned prescription of suppressive antibiotics to treat PJI of the index joint for > 12 months post Stage-2 surgery;
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 (IV) 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 (i.e., chronic kidney disease Stage 4 or 5 or patients with an estimated glomerular filtration rate <30 mL/min);
Patients on chemotherapy for malignant disease;
Patients on systemic glucocorticoid therapy (prednisone >10 mg/day or equivalent);
Patients who are immunodeficient (e.g., splenectomy, sickle cell anemia, Stage 3 human immunodeficiency virus infection, primary immunodeficiency disease), except patients who are immunodeficient 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 with a fungal PJI as determined by one or more positive fluid and/or tissue cultures;
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;
Patients who are incarcerated or are facing impending incarceration;
Patients who have been in treatment or referred to 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 the conduct of the study;
Patients who are judged by the Study Site PI 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 or the APEX study (JPS-0301);
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 planned surgery and ending at least 14 days following planned 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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental	VT-X7 Treatment System	Local antibiotic irrigation via the VT-X7 Treatment System adjuvant to two-stage exchange arthroplasty per SOC.
Experimental	Two-stage exchange arthroplasty	Local antibiotic irrigation via the VT-X7 Treatment System adjuvant to two-stage exchange arthroplasty per SOC.
Experimental	Experimental Antibiotics	Local antibiotic irrigation via the VT-X7 Treatment System adjuvant to two-stage exchange arthroplasty per SOC.
Control	Two-stage exchange arthroplasty	SOC 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.
Control	SOC Antibiotics	SOC 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.

Primary Outcome Measures

Name	Time	Method
Overall Treatment Success	180 days	* Stage 2 revision prosthesis implanted and * Absence of PJI post-Stage 2 and * Absence of continued antibiotic therapy for treatment or prophylaxis of PJI and * Absence of revision surgery of the affected joint pre- and post-Stage 2 and * Absence of mortality.

Secondary Outcome Measures

Name	Time	Method
Overall Treatment Success	365 days	* Stage 2 revision prosthesis implanted and * Absence of PJI post-Stage 2 and * Absence of continued antibiotic therapy for treatment or prophylaxis of PJI and * Absence of revision surgery of the affected joint pre- and post-Stage 2 and * Absence of mortality.
Adverse Event Rate	365 days	Comparison of the cumulative proportion of subjects with reported adverse events between the study arms.
Survival	365 days	Comparison of the survival between the study arms.
Quality Adjusted Life Years	365 days	Comparison of Quality Adjusted Life Years between the study arms as estimated by EQ-5D-3L.

Trial Locations

Locations (19): University of Missouri
🇺🇸
Columbia, Missouri, United States
The Ohio State University Medical Center
🇺🇸
Columbus, Ohio, United States
Harbor UCLA Medical Center
🇺🇸
Los Angeles, California, United States
Kennedy White Orthopaedic Center
🇺🇸
Sarasota, Florida, United States
Cleveland Clinic Florida
🇺🇸
Weston, Florida, United States
NYU Langone Health
🇺🇸
New York, New York, United States
OrthoCarolina
🇺🇸
Charlotte, North Carolina, United States
Cleveland Clinic
🇺🇸
Cleveland, Ohio, United States
Rothman Orthopaedic Institute
🇺🇸
Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical Center
🇺🇸
Pittsburgh, Pennsylvania, United States
Houston Methodist Medical Center
🇺🇸
Houston, Texas, United States
University of Virginia Health
🇺🇸
Charlottesville, Virginia, United States
Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
Covenant Medical Center
🇺🇸
Saginaw, Michigan, United States
Banner - University Medical Center Phoenix
🇺🇸
Phoenix, Arizona, United States
University of Cincinnati
🇺🇸
Cincinnati, Ohio, United States
Bethesda North Hospital - TriHealth Hatton Research
🇺🇸
Cincinnati, Ohio, United States
INTEGRIS Health Southwest Medical Center
🇺🇸
Oklahoma City, Oklahoma, United States
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States