Clinical trial NCT04662632: Abbreviated Protocol for Two-Stage Exchange
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
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: 2020-12-10
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: 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.


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)

Primary outcomes:
measure: Composite endpoint of Overall Success at 90 days
timeFrame: 90 days
Secondary outcomes:
measure: Composite endpoint of Overall Success at 180 days
timeFrame: 180 days
measure: Composite endpoint of Overall Success at 365 days consisting of:
timeFrame: 365 days
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: University of Arizona, Phoenix
state: Arizona
city: Torrance
country: United States
facility: Harbor-UCLA Medical Center
state: California
city: Washington
country: United States
facility: VA Medical Center
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic
state: Florida
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Saginaw
country: United States
facility: Covenant Medical Center
state: Michigan
city: New York
country: United States
facility: New York University
state: New York
city: New York
country: United States
facility: Columbia
state: New York
city: Charlotte
country: United States
facility: OrthoCarolina Research Institute, Inc
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Oklahoma City
country: United States
facility: Integris Southwest Medical Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Rothman Orthopaedic Institute
state: Pennsylvania
city: Plano
country: United States
facility: Texas Health Presbyterian
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Charlottesville
country: United States
facility: UVA Orthopedics Center
state: Virginia
Study officials:
affiliation: Ortho Carolina
name: Bryan Springer, MD
role: PRINCIPAL_INVESTIGATOR
References: