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Abbreviated Protocol for Two-Stage Exchange (APEX)

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ClinicalTrials.gov Identifier: NCT04662632
Recruitment Status : Active, not recruiting
First Posted : December 10, 2020
Last Update Posted : September 24, 2021
Sponsor:
Information provided by (Responsible Party):
Osteal Therapeutics, Inc.

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
Prosthetic Joint Infection Combination Product: VT-X7 Treatment System Drug: SOC Procedure: Two-stage exchange arthroplasty Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : July 1, 2021
Estimated Primary Completion Date : August 2023
Estimated Study Completion Date : August 2023

Resource links provided by the National Library of Medicine


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).




Primary Outcome Measures :
  1. Composite endpoint of Overall Success at 90 days [ Time Frame: 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 [ Time Frame: 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: [ Time Frame: 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.



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Ages Eligible for Study:   22 Years to 84 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 (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 6 months;
  • 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 >5 mg/day or equivalent);
  • Patients with immunodeficiency (e.g., splenectomy, sickle cell anemia, Stage 3 human immunodeficiency virus (HIV) infection, primary humoral immunodeficiency, or bone marrow or other transplantation);
  • 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 PJI pathogen that is not considered susceptible to vancomycin HCl or tobramycin sulfate, per the Principal Investigator's (PI's) opinion, including fungal infection;
  • Patients who have a "megaprosthesis" addressing a large skeletal defect in 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 are currently abusing drugs or alcohol or have been in 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 have participated in another clinical study of another investigational drug or investigational device within the past 30 days;
  • Patients who are judged by the PI to be unsuitable for the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04662632


Locations
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Sponsors and Collaborators
Osteal Therapeutics, Inc.
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Responsible Party: Osteal Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04662632    
Other Study ID Numbers: JPS-0301
First Posted: December 10, 2020    Key Record Dates
Last Update Posted: September 24, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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
Keywords provided by Osteal Therapeutics, Inc.:
Hip
Knee
Biofilm
Minimum-biofilm-eradication-concentration
Additional relevant MeSH terms:
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Infections