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APEX: Abbreviated Protocol for Two-Stage Exchange

Sponsor
Osteal Therapeutics, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04662632
Collaborator
(none)
76
Enrollment
17
Locations
2
Arms
21
Anticipated Duration (Months)
4.5
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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. 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 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 (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.

Condition or Disease Intervention/Treatment Phase
  • Combination Product: VT-X7 Treatment System
  • Drug: SOC
  • Procedure: Two-stage exchange arthroplasty
 Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
76 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Participant)
Masking Description:
Patients will be blinded to their randomization arm assignment until the completion of Stage 1 surgery.
Primary Purpose:
Treatment
Official Title:
A Randomized Controlled Trial of Alternating Irrigation of Vancomycin HCl and Tobramycin Sulfate in Patients Undergoing Two-Stage Exchange Arthroplasty for Periprosthetic Joint Infection of the Hip or Knee
Actual Study Start Date :
Nov 1, 2021
Anticipated Primary Completion Date :
Aug 1, 2023
Anticipated Study Completion Date :
Aug 1, 2023

Arms and Interventions

Arm Intervention/Treatment
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
Seven-day local antibiotic irrigation (alternating tobramycin sulfate and vancomycin HCl) via the VT-X7 Knee or Hip Spacer with alternating NPWT.

Procedure: Two-stage exchange arthroplasty
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).
Active Comparator: Control

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.

Drug: SOC
Forty-two days (minimum) systemic antibiotic administration adjuvant to two-stage exchange arthroplasty with temporary antibiotic-impregnated cement spacer per SOC. Antibiotics will be selected by treatment provider and administered in accordance with national and local treatment guidelines.

Procedure: Two-stage exchange arthroplasty
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).

Outcome Measures

Primary Outcome Measures

  1. Composite endpoint of Overall Success at 90 days [90 days]

    Composite endpoint of Overall Success at 90 days consisting of: Stage 2 revision prosthesis implanted; Absence of PJI* post-Stage 2; Absence of reoperation*** of the affected joint pre- or post- Stage 2; and Absence of mortality. If clinical evidence of infection is present post-Stage 2 surgery, use ICMMI 2018 for definitive PJI confirmation. Reoperation includes only procedures to irrigate, debride, and remove or replace the Stage 1 spacer or any Stage 2 implant component.

Secondary Outcome Measures

  1. Composite endpoint of Overall Success at 180 days [180 days]

    Composite endpoint of Overall Success at 180 days consisting of: Stage 2 revision prosthesis implanted; Absence of PJI* post-Stage 2; Absence of continued antibiotic therapy for treatment or prophylaxis of PJI **; Absence of reoperation*** of the affected joint pre- and post-Stage 2; and Absence of mortality. If clinical evidence of infection is present post-Stage 2 surgery, use ICMMI 2018 for definitive PJI confirmation. Continued antibiotic therapy includes antibiotic therapy at 180 days or beyond 12 weeks post-Stage 2 surgery, excluding antibiotics for documented pre-procedural prophylaxis or infection other than PJI. Reoperation includes only procedures to irrigate, debride, remove or replace the Stage 1 spacer or any Stage 2 implant component.

  2. Composite endpoint of Overall Success at 365 days consisting of: [365 days]

    Composite endpoint of Overall Success at 365 days consisting of: Stage 2 revision prosthesis implanted; Absence of PJI* post-Stage 2; Absence of continued antibiotic therapy for treatment or prophylaxis of PJI **; Absence of reoperation*** of the affected joint pre- and post-Stage 2; and Absence of mortality. If clinical evidence of infection is present post-Stage 2 surgery, use ICMMI 2018 for definitive PJI confirmation. Continued antibiotic therapy includes antibiotic therapy at 365 days or beyond 12 weeks post-Stage 2 surgery, excluding antibiotics for documented pre-procedural prophylaxis or infection other than PJI. Reoperation includes only procedures to irrigate, debride, remove or replace the Stage 1 spacer or any Stage 2 implant component.

Eligibility Criteria

Criteria

Ages Eligible for Study:
22 Years to 84 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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 (ICMMI) 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 (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 (chronic kidney disease (CKD) Stage 4 or greater or glomerular filtration rate (GFR) <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 (HIV) infection, primary immunodeficiency disease, except immunodeficiency due to immunosuppressive therapy.

  • Patients who have an allergy to vancomycin HCl 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 NPWT 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 PI;

  • 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) Etenercept (Enbrel) Anakinra (Kineret) Golimumab (Simponi) Secukinimab (Cosentyx) Infliximab (Remicade) Ustekinumab (Stelara) Abatacept (Orencia) Rituximab (Rituxan) Certolizumab (Cimzia) Tofacitinib (Xeljanz) Belimumab (Benlysta)

Contacts and Locations

Locations

Site City State Country Postal Code
1 University of Arizona, Phoenix Phoenix Arizona United States 85004
2 Harbor-UCLA Medical Center Torrance California United States 90502
3 VA Medical Center Washington District of Columbia United States 20422
4 University of Florida Gainesville Florida United States 32611
5 Cleveland Clinic Weston Florida United States 33331
6 University of Kentucky Lexington Kentucky United States 40506
7 Covenant Medical Center Saginaw Michigan United States 48602
8 New York University New York New York United States 10003
9 Columbia New York New York United States 10032
10 OrthoCarolina Research Institute, Inc Charlotte North Carolina United States 28207
11 Cleveland Clinic Cleveland Ohio United States 44195
12 Ohio State University Columbus Ohio United States 43202
13 Integris Southwest Medical Center Oklahoma City Oklahoma United States 73103
14 Rothman Orthopaedic Institute Philadelphia Pennsylvania United States 19107
15 Texas Health Presbyterian Plano Texas United States 75093
16 University of Utah Salt Lake City Utah United States 84108
17 UVA Orthopedics Center Charlottesville Virginia United States 22903

Sponsors and Collaborators

  • Osteal Therapeutics, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Osteal Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT04662632
Other Study ID Numbers:
  • JPS-0301
First Posted:
Dec 10, 2020
Last Update Posted:
Aug 24, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
Yes
Keywords provided by Osteal Therapeutics, Inc.
Hip
Knee
Biofilm
Minimum-biofilm-eradication-concentration
Additional relevant MeSH terms:
Infections

Study Results

No Results Posted as of Aug 24, 2022