Clinical trial NCT05607030: A Second Trial of the Abbreviated Protocol Two-Stage Exchange
Official title: A Second Randomized Controlled Trial of Alternating Irrigation of Vancomycin Hydrochloride and Tobramycin Sulfate in Patients Undergoing Two-Stage Exchange Arthroplasty for Periprosthetic Joint Infection of the Hip or Knee
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prosthetic-joint Infection
Keywords: Hip
Knee
Biofilm
Minimum-biofilm-eradication-concentration
Lead sponsor: Osteal Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2022-11-07
Enrollment: 76
Sex: ALL
Minimum age (years): 22
Maximum age (years): 84
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Overall Treatment Success
timeFrame: 180 days
Secondary outcomes:
measure: Overall Treatment Success
timeFrame: 365 days
measure: Adverse Event Rate
timeFrame: 365 days
measure: Quality Adjusted Life Years
timeFrame: 365 days
measure: Survival
timeFrame: 365 days
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Banner - University Medical Center Phoenix
state: Arizona
city: Los Angeles
country: United States
facility: Harbor UCLA Medical Center
state: California
city: Sarasota
country: United States
facility: Kennedy White Orthopaedic Center
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Saginaw
country: United States
facility: Covenant Medical Center
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Columbia
country: United States
facility: University of Missouri
state: Missouri
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: Charlotte
country: United States
facility: OrthoCarolina
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cincinnati
country: United States
facility: Bethesda North Hospital - TriHealth Hatton Research
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: INTEGRIS Health Southwest Medical Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Rothman Orthopaedic Institute
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Houston
country: United States
facility: Houston Methodist Medical Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Health
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: The Cleveland Clinic
name: Nicolas Piuzzi, MD
role: PRINCIPAL_INVESTIGATOR
References: