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A Second Trial of the Abbreviated Protocol Two-Stage Exchange (Apex-2)

Primary Purpose

Prosthetic-joint Infection

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
VT-X7 Treatment System
Two-stage exchange arthroplasty
Standard of Care
Sponsored by
Osteal Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prosthetic-joint Infection focused on measuring Hip, Knee, Biofilm, Minimum-biofilm-eradication-concentration

Eligibility Criteria

22 Years - 84 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 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)

Sites / Locations

  • Banner - University Medical Center PhoenixRecruiting
  • Harbor UCLA Medical CenterRecruiting
  • University of Florida Health
  • Kennedy White Orthopaedic CenterRecruiting
  • Cleveland Clinic FloridaRecruiting
  • Covenant Medical CenterRecruiting
  • Mayo ClinicRecruiting
  • University of MissouriRecruiting
  • NYU Langone HealthRecruiting
  • OrthoCarolinaRecruiting
  • University of CincinnatiRecruiting
  • Bethesda North Hospital - TriHealth Hatton Research
  • Cleveland ClinicRecruiting
  • The Ohio State University Medical CenterRecruiting
  • INTEGRIS Health Southwest Medical CenterRecruiting
  • Rothman Orthopaedic InstituteRecruiting
  • University of Pittsburgh Medical CenterRecruiting
  • Houston Methodist Medical CenterRecruiting
  • University of Virginia HealthRecruiting
  • Medical College of WisconsinRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Experimental

Control

Arm Description

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

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Adverse Event Rate
Comparison of the cumulative proportion of subjects with reported adverse events between the study arms.
Quality Adjusted Life Years
Comparison of Quality Adjusted Life Years between the study arms as estimated by EQ-5D-3L.
Survival
Comparison of the survival between the study arms.

Full Information

First Posted
October 31, 2022
Last Updated
August 17, 2023
Sponsor
Osteal Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05607030
Brief Title
A Second Trial of the Abbreviated Protocol Two-Stage Exchange
Acronym
Apex-2
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

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 23, 2023 (Actual)
Primary Completion Date
March 31, 2024 (Anticipated)
Study Completion Date
September 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Osteal Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prosthetic-joint Infection
Keywords
Hip, Knee, Biofilm, Minimum-biofilm-eradication-concentration

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Participant
Masking Description
Patients will be blinded to their randomization arm assignment until the completion of Stage 1 surgery.
Allocation
Randomized
Enrollment
76 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental
Arm Type
Experimental
Arm Description
Local antibiotic irrigation via the VT-X7 Treatment System adjuvant to two-stage exchange arthroplasty per SOC.
Arm Title
Control
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Combination Product
Intervention Name(s)
VT-X7 Treatment System
Intervention Description
Seven-day local antibiotic irrigation (alternating vancomycin hydrochloride and tobramycin sulfate) via the temporary VT-X7 Knee or Hip Spacer.
Intervention Type
Procedure
Intervention Name(s)
Two-stage exchange arthroplasty
Intervention Description
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
Drug
Intervention Name(s)
Standard of Care
Intervention Description
Forty-two days (minimum) systemic antibiotic administration adjuvant to two-stage exchange arthroplasty with temporary antibiotic-impregnated cement spacer per standard of care (SOC). Antibiotics will be selected by treatment provider and administered in accordance with national and local treatment guidelines.
Primary Outcome Measure Information:
Title
Overall Treatment Success
Description
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.
Time Frame
180 days
Secondary Outcome Measure Information:
Title
Overall Treatment Success
Description
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.
Time Frame
365 days
Title
Adverse Event Rate
Description
Comparison of the cumulative proportion of subjects with reported adverse events between the study arms.
Time Frame
365 days
Title
Quality Adjusted Life Years
Description
Comparison of Quality Adjusted Life Years between the study arms as estimated by EQ-5D-3L.
Time Frame
365 days
Title
Survival
Description
Comparison of the survival between the study arms.
Time Frame
365 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
22 Years
Maximum Age & Unit of Time
84 Years
Accepts Healthy Volunteers
No
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 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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Latania Chura
Phone
503-380-8623
Email
lchura@ostealtx.com
First Name & Middle Initial & Last Name or Official Title & Degree
Clay Cohorn
Phone
214-957-9353
Email
ccohorn@ostealtx.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicolas Piuzzi, MD
Organizational Affiliation
The Cleveland Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Banner - University Medical Center Phoenix
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85006
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marleny Munoz
Email
marlenymunoz@arizona.edu
First Name & Middle Initial & Last Name & Degree
Brock Walker, MD
Facility Name
Harbor UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90502
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elaine Santana
Email
esantana@lundquist.org
First Name & Middle Initial & Last Name & Degree
Lewis Moss, MD
Facility Name
University of Florida Health
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32608
Country
United States
Individual Site Status
Withdrawn
Facility Name
Kennedy White Orthopaedic Center
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34232
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jesse D'Alessio
Email
jdalessio@gulfcoast-research.com
First Name & Middle Initial & Last Name & Degree
Edward Stolarski, MD
Facility Name
Cleveland Clinic Florida
City
Weston
State/Province
Florida
ZIP/Postal Code
33331
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jesus Villa
Email
villaj2@ccf.org
First Name & Middle Initial & Last Name & Degree
Carlos Higuera-Rueda, MD
Facility Name
Covenant Medical Center
City
Saginaw
State/Province
Michigan
ZIP/Postal Code
48602
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Melanie Akin
Email
makin@chs-mi.com
First Name & Middle Initial & Last Name & Degree
Brian Debeaubien, MD
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Riley Voll
Email
voll.riley@mayo.edu
First Name & Middle Initial & Last Name & Degree
Rafael Sierra, MD
Facility Name
University of Missouri
City
Columbia
State/Province
Missouri
ZIP/Postal Code
65212
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vicky Jones
Email
jonesvicki@health.missouri.edu
First Name & Middle Initial & Last Name & Degree
Elie Ghanem, MD
Facility Name
NYU Langone Health
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daniel Waren
Email
daniel.waren@nyulangone.org
First Name & Middle Initial & Last Name & Degree
Ran Schwarzkopf, MD
Facility Name
OrthoCarolina
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28207
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Taylor Rowe
Email
taylor.rowe@orthocarolina.com
First Name & Middle Initial & Last Name & Degree
Bryan Springer, MD
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kimberly Hasselfield
Email
hasselky@ucmail.uc.edu
First Name & Middle Initial & Last Name & Degree
Toan Le, MD
Facility Name
Bethesda North Hospital - TriHealth Hatton Research
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45242
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tammy Roads
Email
tammy_roads@trihealth.com
First Name & Middle Initial & Last Name & Degree
Steven Goldfarb, MD
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
PJ Rullan
Email
rullanp@ccf.org
First Name & Middle Initial & Last Name & Degree
Nicholas Piuzzi, MD
Facility Name
The Ohio State University Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nikhil Punwani
Email
nikhil.punwani@osumc.edu
First Name & Middle Initial & Last Name & Degree
Andrew Glassman, MD
Facility Name
INTEGRIS Health Southwest Medical Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stephanie Plummer
Email
splummer122803@gmail.com
First Name & Middle Initial & Last Name & Degree
Bradley Reddick, DO
Facility Name
Rothman Orthopaedic Institute
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alicia Reyes
Email
alicia.reyes@rothmanortho.com
First Name & Middle Initial & Last Name & Degree
Max Courtney, MD
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrew Frear
Email
freara3@upmc.edu
First Name & Middle Initial & Last Name & Degree
Kenneth Urish, MD
Facility Name
Houston Methodist Medical Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thomas Sullivan
Email
tsullivan@houstonmethodist.org
First Name & Middle Initial & Last Name & Degree
Kwan Park, MD
Facility Name
University of Virginia Health
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22903
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eric McVey
Email
emcvey@virginia.edu
First Name & Middle Initial & Last Name & Degree
Ian Duensing, MD
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nick Giebel
Email
ngiebel@mcw.edu
First Name & Middle Initial & Last Name & Degree
William Lutes, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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A Second Trial of the Abbreviated Protocol Two-Stage Exchange

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