Summary

for people ages 18 years and up (full criteria)
healthy people welcome
study started
estimated completion
Jeffrey Barry

Description

Summary

Purpose of Study: In order to improve upon the modest results seen in irrigation and debridement for periprosthetic infection and limit the number of surgical procedures performed we ask if the use of intraosseous regional administration of antibiotics at the time of irrigation and debridement would further improve the results of irrigation debridement for prosthetic joint infection. Impact Question: How will this study benefit the patient? Currently when an I&D fails, the patient needs to undergo two more major procedures: 1) implant removal and 2) reimplantation of the prosthesis. Since I&D currently fails up to 2/3 of the time, any improvement will decrease the number of patients having to go through two procedures to cure their infection.

Details

Type of Study:

This is a two-arm, multi-center, randomized, superiority clinical trial.

Treatment Group & Comparison (Control) Group:

  • The treatment group includes any patient with an acute perioperative periprosthetic infection, or acute hematogenous infection with a gram positive organism sensitive to vancomycin and treated with intraoperative intraosseous vancomycin. Additionally, patients will be treated with at least 4 weeks of IV antibiotics under guidance of an infectious disease specialist, and indefinite antibiotic chronic suppression.
  • The control group includes any patient with an acute perioperative periprosthetic, or acute hematogenous infection with a vancomycin sensitive gram positive organism treated with intravenous vancomycin. Additionally, patients will be treated with at least 4 weeks of IV antibiotics, and indefinite antibiotic chronic suppression under guidance of an infectious disease specialist.
  • Therefore, the only difference between the study groups is the route of administration of intraoperative vancomycin.

Surgical and Antibiotic Administration Technique:

Initially, all patients will receive standard weight based cefazolin (1 gram for patients < 80kg, 2 grams for patients between 80-120kg, and 3 grams for patients over 120kg) preoperatively. Our protocol for MRSA positive patients is to use cefazolin and vancomycin preoperatively. Because irrigation and debridement in patients with gram positive infections are frequently done urgently before exact organism identification and sensitivities are available it is important to cover the patient broadly with cefazolin and vancomycin initially.

The control group (systemic IV therapy) will receive vancomycin preoperatively (15mg/kg) based on actual body weight (maximum 2 grams) IV beginning 60 to 120 minutes preoperatively. The interventional group will receive post debridement intraosseous vancomycin as described below. In total knee infections a pneumatic tourniquet must be used for the procedure. After entering the hip or knee joint the following process is followed:

  1. Fluid is collected in four syringes and placed into two sets of aerobic and anaerobic adult blood culture bottles,
  2. Two synovial tissue cultures from different areas of the joint are obtained and sent for culture,
  3. If not enough fluid is obtained send an additional tissue culture,
  4. Remaining tissue is sent for final pathologic analysis at the end of the case.

After obtaining cultures radical synovial debridement is performed debriding the inner surface of the entire hip or knee capsule including the posterior capsule of the knee and anterior capsule of the hip. Modular parts will be removed, that is the femoral head and polyethylene liner in hips and the polyethylene insert for knees.

Debridement and Irrigation Protocol:

After a complete synovectomy is performed along with extraction of modular parts any exposed metallic parts will be scrubbed with a sterile brush soaked in dilute betadine. A 5-step irrigation protocol will then be used for all surgeries:

  1. Pulse lavage with 3 liters of normal saline (NS),
  2. Lavage with 100 cc's of 3% H202 and 100 cc's of sterile water, a 50/50 solution left in wound for 2 minutes,
  3. Lavage 3 liters NS,
  4. Lavage with 1 liter of dilute, sterile Betadine (22.5 ml Betadine/liter NS) - left in wound for 3 minutes
  5. Pulse lavage with 3 liters of NS

After debridement and irrigation the interventional group will receive intraosseous vancomycin 500mg in 150ml of normal saline. This dose was selected based on the studies of Young (10) and Clarke (11) who used this dose in two high risk groups (revision TKA and high BMI patients) with no significant side effects or red man syndromes. This solution will be prepared by the hospital pharmacy and administered via an EZ-IO intraosseous cannula (Teleflex Corp, San Antonio TX: Food and Drug Administration approved). In total knees the cannula will be placed in the proximal medial tibia using a starter drill slightly smaller than the diameter of the cannula to ensure a press fit just distal to the tibia implant in the vicinity of the pes anserine tendons. 75ccs of the vancomycin solution will be injected as a bolus. Subsequent to this the remaining 75ccs will be placed in the distal femur just proximal to the femoral component evenly split between the medial and lateral femoral condyles. In hips the cannula is placed just distal to the femoral component and 75ccs of the vancomycin solution is injected as a bolus. The remaining 75ccs is placed into the supra acetabular region through the cannula.

After irrigation and debridement the wound will be closed over a betadine soaked lap sponge placed between the components. Contaminated drapes and instruments will be removed and the patient will be re-prepped with new drapes. New instruments will be used to insert the new modular parts. After opening the wound and prior to inserting new modular parts the wound will be irrigated this time with the following regime:

  1. Pulse lavage with 3 liters of normal saline (NS),
  2. Lavage with 100 cc's of 3% H202 and 100 cc's of sterile water, a 50/50 solution left in wound for 2 minutes,
  3. Lavage 1 liters NS,
  4. Lavage with 1 liter of dilute, sterile Betadine (22.5 ml Betadine/liter NS) - left in wound for 3 minutes
  5. Pulse lavage with 3 liters of NS

After the modular parts are reinserted the wound is closed with monofilament sutures over drains.

Post-operative treatment will be managed by an infectious disease specialist with at least four weeks of intravenous antibiotics followed by indefinite chronic suppression as recommended by the Musculoskeletal Infection Society (Table 1). Baseline creatinine will be obtained preoperatively and on postop days 1 and 2. Infectious disease consultants will monitor peak and trough levels based on the specific antibiotic administered and they will adjust dosage as indicated.

Keywords

Joint Infection Anti-Bacterial Agents Vancomycin Antibiotics, Antitubercular Intraoperative Intraosseous Vancomycin

Eligibility

You can join if…

Open to people ages 18 years and up

  1. Any patient with an acute perioperative periprosthetic infection or an acute hematogenous infection indicated for an irrigation debridement procedure of a hip or knee infection with a gram positive organism susceptible to vancomycin.

The patient must be deemed infected per MSIS criteria:

  1. A sinus communicating with the prosthesis OR
  2. Two positive cultures obtained from the prosthesis OR
  3. 3 of 5 criteria: (i) Elevated ESR (>30mm/hr) and CRP (>10mg/L) (ii) Elevated synovial leukocyte count (>3000 cells/μL) or change of ++ on leukocyte esterase strip (iii) Elevated synovial neutrophil percentage (>80%) (iv) One positive culture (v) Positive histological analysis of periprosthetic tissue (>5 neutrophils per high power field in 5 high power fields x400)

II. Acute perioperative periprosthetic infection in the first 90 days following primary surgery.

III. Acute hematogenous infection with symptoms less than four weeks.

You CAN'T join if...

  1. Any patient with a chronic infection or a surgical wound that cannot be closed.

II. Patients with PJI greater than 90 days following primary surgery. III. Acute hematogenous infection with symptoms greater than four weeks IV. Know hypersensitivity to Vancomycin V. Major Renal disease defined as creatinine > 1.5 (See previous comments, No Red Man syndrome in 2 subsequent studies on intraosseous vancomycin in revision TKA and High BMI patients respectively (10,11). Additional systematic levels were 8 times lower than IV Vancomycin.

VI. Unable to use a tourniquet due to vascular disease

Lead Scientist

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
OrthoCarolina Research Institute, Inc.
ID
NCT03713528
Phase
Phase 4
Study Type
Interventional
Last Updated