Vancomycin Or Trimethoprim/Sulfamethoxazole for Methicillin-resistant Staphylococcus Aureus Osteomyelitis

A Prospective, Randomized Trial Comparing Vancomycin With Trimethoprim/Sulfamethoxazole for the Treatment of MRSA Osteomyelitis

The primary question of this study is to understand if trimethoprim-sulfamethoxazole (TMP-SMX) is as effective as vancomycin for treating methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis.

Study Overview

• Status: Completed
• Conditions: Methicillin-resistant Staphylococcus Aureus; Osteomyelitis
• Intervention / Treatment: Drug: trimethoprim-sulfamethoxazole; Drug: vancomycin

Detailed Description

Treatment of osteomyelitis is hampered by a paucity of evidence from prospective clinical trials with randomized treatment arms. Furthermore, previous randomized or observational trials have enrolled small numbers of subjects and thus often had non-definitive findings. One of the most common causes of osteomyelitis is Staphylococcus aureus. Over the past 10 years, rates of methicillin-resistant S. aureus (MRSA) have risen dramatically. Vancomycin is currently the treatment of choice for treating MRSA. While vancomycin is effective, it is only available in intravenous formulation and has renal and bone marrow toxicities. There is a critical need for effective, oral, cheap drugs for the treatment of MRSA. Trimethoprim-sulfamethoxazole (TMP-SMX) is a drug with several advantageous properties for the treatment of MRSA osteomyelitis. To address this question regarding optimal treatment of MRSA osteomyelitis, we designed a prospective, randomized trial comparing TMP-SMX with vancomycin for the treatment of MRSA osteomyelitis.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98104
      • University of Washington

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Culture-proven MRSA, obtained in operating room or sterile biopsy procedure from bone site. The infection and sampling site can either be within bone or a deep soft-tissue site that is contiguous with bone; OR radiographic abnormality consistent with osteomyelitis in conjunction with a positive blood culture for MRSA.
2. Surgical debridement of infection site, as needed.
3. Subject is capable of providing written informed consent.
4. Subject is at least 18 years of age.
5. Subject capable of receiving outpatient parenteral therapy for 12 weeks.

Exclusion Criteria:

1. Hypersensitivity to TMP-SMX or vancomycin.
2. S. aureus resistant to TMP-SMX or vancomycin.
3. Osteomyelitis that develops directly from a chronic, open wound.
4. Polymicrobial culture(the only exception is if coagulase-negative staphylococcus is present in the culture and the clinical assessment is that it is a contaminant).
5. Subject has a positive pregnancy test at study enrollment.
6. Convicted felon currently in prison.
7. Baseline renal or hepatic insufficiency that would preclude administration of study drugs.
8. Active injection drug use without safe conditions to administer intravenous antibiotics for 3 months.
9. Anticipated use of antibiotics for greater than 14 days for an infection other than osteomyelitis.

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: Trimethoprim-sulfamethoxazole; trimethoprim-sulfamethoxazole, double strength, 2-3 tabs twice a day by mouth for 6-12 weeks	Drug: trimethoprim-sulfamethoxazole; trimethoprim/sulfamethoxazole 320/1600 mg po bid; Drug: vancomycin; 1g iv bid
Active Comparator: Vancomycin; Vancomycin, dosage to be determined by serum levels, medication provided by vein and duration 6-12 weeks	Drug: vancomycin; 1g iv bid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical cure	No clinical or radiographic evidence of infection at 12 months	12 months

Collaborators and Investigators

• Sponsor: University of Washington
• Investigators: Principal Investigator: Timothy H. Dellitt, MD, UW; Principal Investigator: Jeanne Chan, PharmD, MPH, UW; Principal Investigator: Matthew Golden, MD, MPH, UW; Principal Investigator: M. Bradford Henley, MD, UW; Principal Investigator: Jeanne M Marrazzo, MD, MPH, UW; Principal Investigator: Lisa Taitsman, MD, UW; Principal Investigator: Thomas R Hawn, MD, PhD, UW; Principal Investigator: Robert D Harrington, MD, UW; Principal Investigator: Christian Ramers, MD, University of Washington

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2006
• Primary Completion (Actual): May 1, 2007
• Study Completion (Actual): May 1, 2007

Study Registration Dates

• First Submitted: May 9, 2006
• First Submitted That Met QC Criteria: May 9, 2006
• First Posted (Estimate): May 11, 2006

Study Record Updates

• Last Update Posted (Actual): April 11, 2023
• Last Update Submitted That Met QC Criteria: April 7, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Vancomycin; Trimethoprim-Sulfamethoxazole Combination
• Additional Relevant MeSH Terms: Infections; Musculoskeletal Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Bone Diseases; Bone Diseases, Infectious; Staphylococcal Infections; Osteomyelitis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Folic Acid Antagonists; Anti-Dyskinesia Agents; Anti-Infective Agents, Urinary; Renal Agents; Cytochrome P-450 CYP2C8 Inhibitors; Vancomycin; Trimethoprim; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination
• Other Study ID Numbers: 27915; 05-6396-B 01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes