Or v IV Antibiotics for Infection

Oral vs Intravenous Antibiotics for Treatment of Periprosthetic Joint Infection

Management of periprosthetic joint infection (PJI) commonly includes 6 weeks of intravenous (IV) antibiotics after surgical treatment. However, there is little evidence to suggest that oral (PO) therapy results in worse outcomes. This study aims to determine whether or not PO antibiotics are non-inferior to IV antibiotics in treating PJI. The study is a multicenter, parallel-group, randomized (1 : 1), open-label, non-inferiority trial. The non-inferiority margin will be set at 10%. Adults with a clinical diagnosis of PJI according to the International Consensus Meeting (ICM) criteria who would ordinarily receive at least 6 weeks of antibiotics and have received ≤ 7 days of IV therapy from surgery will be included. A total of 308 participants will be centrally computer-randomized to PO or IV antibiotics to complete the first 6 weeks of therapy. Follow-on PO therapy will be permitted in either arm. The primary outcome is the proportion of participants experiencing treatment failure within 1 year. An associated cost-effectiveness evaluation including complications, resource utilization and quality-of-life data will be performed.

Study Overview

• Status: Enrolling by invitation
• Conditions: Joint Infection
• Intervention / Treatment: Drug: Bactrim; Drug: Cefadroxil; Drug: Doxycycline Hcl; Drug: Clindamycin

• Study Type: Interventional
• Enrollment (Anticipated): 308
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Rothman Orthopaedic Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• aged ≥ 18 years
• willing and able to give informed consent

• primary THA or TKA diagnosed with PJI based on International Consensus Meeting criteria

  1. A sinus communicating with the prosthesis OR
  2. Two positive cultures obtained from the prosthesis OR
  3. 3 of 5 criteria:
• Elevated ESR (>30mm/hr) and CRP (>10mg/L)
• Elevated synovial leukocyte count (>3000 cells/µL) or change of ++ on leukocyte esterase strip
• Elevated synovial neutrophil percentage (>80%)
• One positive culture
• Positive histological analysis of periprosthetic tissue (>5 neutrophils per high power field in 5 high power fields x400)
• PJI treated by debridement and implant retention, or excision of the prosthetic joint (with or without planned reimplantation)
• received ≤ 7 days of IV therapy after an appropriate surgical intervention

Exclusion Criteria:

• Previously treated for native septic arthritis or PJI in the same joint
• S. aureus bacteremia on presentation or within the previous month
• clinical, histological or microbiological evidence of mycobacterial, fungal or parasitic etiology of the infection
• any other concomitant infection that, in the opinion of the clinician responsible for the patient, requires a prolonged course of IV antibiotic therapy (e.g. bacterial endocarditis, mediastinal infection, central nervous system infection)
• septic shock or systemic features that, in the opinion of the clinician responsible for the patient, requires a course of IV antibiotic therapy (the patient could be re-evaluated if these features resolved)
• an infection for which there are no suitable antibiotic choices to permit randomization between the two arms of the trial (e.g. when organisms are only sensitive to IV antibiotics or PO antibiotics)
• unlikely to comply with trial requirements following randomization in the opinion of the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oral Antibiotics; Participant will receive 6 weeks of oral antibiotic therapy to treat their infection. The type of antibiotic given will be at the discretion of the infectious disease doctor.	Drug: Bactrim; Bactrim will be given for 6 weeks to treat joint infection; Drug: Cefadroxil; Cefadroxil will be given for 6 weeks to treat joint infection; Drug: Doxycycline Hcl; Doxycycline HCl will given for 6 weeks to treat joint infection; Drug: Clindamycin; Clindamycin will given for 6 weeks to treat joint infection
Active Comparator: Intravenous Antibiotics; Participant will receive 6 weeks of intravenous (IV) antibiotic therapy to treat their infection. The type of antibiotic given will be at the discretion of the infectious disease doctor.	Drug: Bactrim; Bactrim will be given for 6 weeks to treat joint infection; Drug: Cefadroxil; Cefadroxil will be given for 6 weeks to treat joint infection; Drug: Doxycycline Hcl; Doxycycline HCl will given for 6 weeks to treat joint infection; Drug: Clindamycin; Clindamycin will given for 6 weeks to treat joint infection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Postoperative Infections	The investigator will measure the incidence of postoperative infections in participants treated with oral antibiotics versus those treated with intravenous antibiotics	2 years

Collaborators and Investigators

• Sponsor: Rothman Institute Orthopaedics

Study record dates

Study Major Dates

• Study Start (Anticipated): January 25, 2021
• Primary Completion (Anticipated): January 25, 2023
• Study Completion (Anticipated): January 25, 2023

Study Registration Dates

• First Submitted: January 22, 2021
• First Submitted That Met QC Criteria: January 22, 2021
• First Posted (Actual): January 26, 2021

Study Record Updates

• Last Update Posted (Actual): January 26, 2021
• Last Update Submitted That Met QC Criteria: January 22, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Anti-Infective Agents, Urinary; Renal Agents; Doxycycline; Clindamycin; Clindamycin palmitate; Clindamycin phosphate; Trimethoprim, Sulfamethoxazole Drug Combination; Cefadroxil
• Other Study ID Numbers: JPAR 20D.1085

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes