A Second Trial of the Abbreviated Protocol Two-Stage Exchange

NCT05607030 | Completed Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: OTX-0302
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 19

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.

Conditions

Prosthetic-joint Infection

Keywords

Hip; Knee; Biofilm; Minimum-biofilm-eradication-concentration

Outcome Measures

Primary Outcomes (1)

• Overall Treatment Success

  * 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.

  180 days

Secondary Outcomes (4)

• Overall Treatment Success

  365 days

• Adverse Event Rate

  365 days

• Quality Adjusted Life Years

  365 days

• Survival

  365 days

Study Arms (2)

Experimental

EXPERIMENTAL

Local antibiotic irrigation via the VT-X7 Treatment System adjuvant to two-stage exchange arthroplasty per SOC.

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

Control

ACTIVE COMPARATOR

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.

Procedure: Two-stage exchange arthroplasty; Drug: SOC Antibiotics

Interventions

VT-X7 Treatment System COMBINATION_PRODUCT

Seven-day local antibiotic irrigation (alternating vancomycin hydrochloride and tobramycin sulfate) via the temporary VT-X7 Knee or Hip Spacer.

Experimental

Two-stage exchange arthroplasty 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.

Control; Experimental

SOC Antibiotics DRUG

Administration of at least 6 weeks of systemic antibiotics post-Stage 1 surgery followed by a 2-week antibiotic holiday before the Stage 2 surgery. After Stage 2 surgery, administration of at least 12 weeks of systemic antibiotics. Antibiotics will be selected by the treatment provider based on the infecting organism and administered per national and local treatment guidelines.

Control

Experimental Antibiotics DRUG

After Stage 2 surgery, administration of at least 12 weeks of systemic antibiotics. Antibiotics will be selected by the treatment provider based on the infecting organism and administered per national and local treatment guidelines.

Experimental

Eligibility Criteria

• Age: 22 Years - 84 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Scheduled for two-stage exchange arthroplasty due to hip or knee periprosthetic joint infection (PJI)
• Signed informed consent
• 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

You may not qualify if:

• 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;

Sponsors & Collaborators

• Osteal Therapeutics, Inc.: lead

Study Sites (19)

Banner - University Medical Center Phoenix

Phoenix, Arizona, 85006, United States

Location

Harbor UCLA Medical Center

Los Angeles, California, 90502, United States

Location

Kennedy White Orthopaedic Center

Sarasota, Florida, 34232, United States

Location

Cleveland Clinic Florida

Weston, Florida, 33331, United States

Location

Covenant Medical Center

Saginaw, Michigan, 48602, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

University of Missouri

Columbia, Missouri, 65212, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

OrthoCarolina

Charlotte, North Carolina, 28207, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

Bethesda North Hospital - TriHealth Hatton Research

Cincinnati, Ohio, 45242, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

The Ohio State University Medical Center

Columbus, Ohio, 43202, United States

Location

INTEGRIS Health Southwest Medical Center

Oklahoma City, Oklahoma, 73109, United States

Location

Rothman Orthopaedic Institute

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Houston Methodist Medical Center

Houston, Texas, 77030, United States

Location

University of Virginia Health

Charlottesville, Virginia, 22903, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Study Officials

• Nicolas Piuzzi, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Patients will be blinded to their randomization arm assignment until the completion of Stage 1 surgery.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2022
• First Posted: November 7, 2022
• Study Start: January 23, 2023
• Primary Completion: May 20, 2024
• Study Completion: October 30, 2024
• Last Updated: January 7, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (19)