Comparison of Oral Antibiotics For Bone Infections of the Leg and Foot (OSTEO)

Oral Beta-lactams Versus Non-beta-lactamS for Treatment of Lower Extremity Osteomyelitis

The goal of this clinical trial is to compare different classes of oral antibiotics (beta-lactam and non-beta-lactam antibiotics) for the treatment of bone infections of the leg and foot. The hypothesis is that oral beta-lactam antibiotics work as well as oral non-beta-lactam antibiotics to treat these infections. The first step is to assess whether it is possible to perform the trial by determining whether participants can be recruited and followed successfully. If the trial is proven to be possible, it will be expanded to ensure an answer to whether the two antibiotic classes work as well for the treatment of bone infections of the leg and foot.

Study Overview

• Status: Recruiting
• Conditions: Osteomyelitis - Foot; Osteomyelitis of the Foot; Osteomyelitis of Lower Extremities
• Intervention / Treatment: Drug: Oral Beta-Lactam Antibiotic; Drug: Oral Non-Beta-Lactam Antibiotic

• Study Type: Interventional
• Enrollment (Estimated): 1418
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Christopher Kandel, MD; Phone Number: 14164696252; Email: christopher.kandel@tehn.ca

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1Y 4E9
      • Not yet recruiting
      • Ottawa Hospital
      • Contact: Derek MacFadden, MD; Email: dmacfadden@toh.ca
    • Toronto, Ontario, Canada, M5G 2C4
      • Not yet recruiting
      • University Health Network
      • Contact: Email: bryan.coburn@uhn.ca
    • Toronto, Ontario, Canada, M4C 3E7
      • Recruiting
      • Michael Garron Hospital
      • Contact: Christopher Kandel, MD; Phone Number: 4164696252; Email: christopher.kandel@tehn.ca
      • Contact: Mazen Almatry, MBA; Phone Number: +16473940003; Email: Mazen.Almatry@tehn.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adult (> 18 years old)
2. OM of the lower extremity (below the knee) as determined by the treating healthcare provider (clinically and/or radiographically)
3. Expected duration of treatment at least 28 additional days of antibiotic therapy for the infection episode, from the time of enrolment
4. Treating health care team has already transitioned or is willing to transition to oral antibiotic therapy for the remainder of the treatment duration

Exclusion Criteria:

1. Prior enrolment in the OSTEO trial
2. Already received more than 14 days of uninterrupted antibiotic treatment for this episode of OM

3. No beta-lactam or non-beta-lactam option due to any of:

   1. Allergy
   2. Suspected or confirmed antimicrobial resistance
   3. Medical contraindications
   4. Non-modifiable drug-drug interaction risk
4. Need to receive combination antibiotic therapy with both beta-lactam and non-beta-lactam, with the exception of metronidazole and rifampin
5. Prior antibiotic treatment for the same infection in the past 6 months
6. Known pregnancy, planning to become pregnant during the study period, or breastfeeding

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
Experimental: Oral Beta-Lactam Antibiotic	Drug: Oral Beta-Lactam Antibiotic; Participants in this arm are randomized to receive an oral antibiotic from the beta-lactam class (e.g., penicillins or cephalosporins) for the treatment of lower extremity osteomyelitis.
Active Comparator: Oral Non-Beta-Lactam Antibiotic	Drug: Oral Non-Beta-Lactam Antibiotic; Participants in this arm are randomized to receive an oral antibiotic from the non-beta-lactam class (e.g., fluoroquinolones, lincosamides, sulfonamides) for the treatment of lower extremity osteomyelitis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Effectiveness Outcomes	Cure (defined by meeting the criteria of: alive, not currently receiving antibiotics, no antibiotic switch from the assigned regimen and no surgical amputation)	24 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Effectiveness Outcomes	The number of participant deaths.	24 Weeks
Secondary Effectiveness Outcomes	Proportion of participants with an antibiotic switch (oral or IV)	24 weeks
Secondary Effectiveness Outcome	Number and level of amputations	24 weeks
Secondary Effectiveness Outcome	Number of debridement operations	24 weeks
Secondary Effectiveness Outcome	Proportion of participants receiving chronic antibiotics for infection suppression	24 weeks
Secondary Effectiveness Outcome	Total duration of antibiotics (oral and IV) for the initial treatment episode	24 weeks
Secondary Effectiveness Outcome	Number and type of antibiotic-related adverse events	24 weeks
Secondary Effectiveness Outcome	Wound colonization with a pathogen of interest	24 weeks
Secondary Effectiveness Outcome	Any positive clinical bacterial culture	52 weeks
Secondary Effectiveness Outcome	Quality of life measurement at 24 weeks (determined by EQ-5D questionnaire) The EQ-5D is a standardized instrument for measuring health-related quality of life. Scores range from 0 (worst possible health state) to 1 (best possible health state), with higher scores indicating better	24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility Outcome	The proportion of potentially eligible participants approached for the trial who provide consent and are randomized (recruitment rate)	24 weeks
Feasibility Outcome	The proportion of participants who receive an initial dose of an antibiotic from the class to which they were randomly allocated (adherence rate)	24 weeks
Feasibility Outcome	The proportion of participants from whom the primary effectiveness outcome is obtained (complete outcome ascertainment rate).	24 weeks

Collaborators and Investigators

• Sponsor: Michael Garron Hospital
• Collaborators: University Health Network, Toronto; The Ottawa Hospital Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2026
• Primary Completion (Estimated): December 31, 2031
• Study Completion (Estimated): December 31, 2033

Study Registration Dates

• First Submitted: November 24, 2025
• First Submitted That Met QC Criteria: November 24, 2025
• First Posted (Actual): December 5, 2025

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Osteomyelitis; Lower Extremity; Bone Infection; Oral beta-lactams versus non-beta-lactams
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Infections; Bone Diseases, Infectious; Osteomyelitis; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Amides; beta-Lactams; Lactams; Monobactams
• Other Study ID Numbers: IDRU-INT-2024-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Awaiting Research Ethics Board approval of the study.

Drug and device information, study documents

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