Randomized Clinical Trial to Compare a Regimen of Trimethoprim-sulfamethoxazole Plus Rifampicin With a Regimen of Linezolid in the Treatment of Methicillin-Resistant Staphylococcus Aureus (MRSA) Infection

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Stephen Harbarth, University Hospital, Geneva
ClinicalTrials.gov Identifier:
NCT00711854
First received: July 3, 2008
Last updated: August 4, 2014
Last verified: August 2014
  Purpose

MRSA infections often require systemic antibiotic therapy and represent an important healthcare burden. Currently available treatment options are either only available in parenteral form (vancomycin) or expensive (linezolid). Thus, there is an urgent, unmet need to better investigate in-expensive but highly active alternatives to currently recommended standard treatment options. The purpose of the proposed study is to test the hypothesis that a combination of TMP-SMX and rifampicin is not inferior to linezolid for treatment of MRSA infections.


Condition Intervention Phase
MRSA Infection
Drug: trimethoprim-sulfamethoxazole (TMP-SMX)
Drug: Linezolid
Drug: Rifampicin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Clinical Trial to Compare a Regimen of Trimethoprim-sulfamethoxazole (TMP-SMX) Plus Rifampicin With a Regimen of Linezolid in the Treatment of Infections Caused by Methicillin-resistant Staphylococcus Aureus (MRSA)

Resource links provided by NLM:


Further study details as provided by University Hospital, Geneva:

Primary Outcome Measures:
  • Bacteriological and clinical cure [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Treatment costs [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

Enrollment: 150
Study Start Date: January 2009
Study Completion Date: February 2014
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
trimethoprim-sulfamethoxazole (TMP-SMX) plus rifampicin
Drug: trimethoprim-sulfamethoxazole (TMP-SMX)
TMP-SMX (160 mg TMP/ 800 mg SMX IV or PO 3x daily)
Drug: Rifampicin
Rifampicin (600 mg IV or PO once daily)
Active Comparator: 2
Linezolid
Drug: Linezolid
Linezolid (600 mg IV or PO twice daily)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age > 18 years
  2. Patients with clinical signs and symptoms of MRSA-related infection
  3. Culture of MRSA (predominant microorganism in culture) susceptible to all of the following:

    • TMP-SMX
    • rifampicin
    • linezolid
  4. Patient must give written informed consent to participate in the study.

Exclusion Criteria:

  1. Women who are pregnant or nursing
  2. Women who refuse to substitute oral contraception during treatment
  3. Known or suspected hypersensitivity to linezolid, TMP-SMX or rifampicin
  4. Clinical or laboratory evidence of significant impairment of hepatic function, as demonstrated by any of the following criteria:

    • Bilirubin > 3 x upper limit of normal range
    • AST or ALT > 5 x upper limit of normal range
    • Acute hepatitis or proven liver cirrhosis by liver histology
  5. Treatment with other antimicrobials with activity against MRSA for > 72 hours prior to study inclusion
  6. Patients with a high probability of death within the week following study entry
  7. Patients who, in the opinion of the investigator, cannot be relied upon for post-therapy follow-up
  8. Patients requiring alternative antibiotic therapy with anti-MRSA activity. However, if another antibiotic treatment without antistaphylococcal activity is necessary, the patient is acceptable for randomization. In that sense, the use of aztreonam (against Gram negative microorganisms) or metronidazole (against anaerobes) is allowed
  9. Hemodialyzed patients
  10. History of pheochromocytoma, carcinoid syndrome, untreated hyperthyroidism, uncontrolled hypertension, or patients receiving serotonin uptake inhibitors
  11. Severe thrombocytopenia (< 50.000 platelets)
  12. Left-sided endocarditis with a poor prognosis (patients aged over 50; cerebral embolism)
  13. Chronic osteomyelitis without surgical debridement; superinfected indwelling foreign body, deliberately kept in place
  14. Patients with severe sepsis or septic shock due to MRSA bacteremia
  15. Patients who receive any of the following drugs, which cannot be substituted or temporarily withdrawn: adrenergic and serotonergic agents, tramadol, pethidine, duloxetine, venlafaxine, milnacipran, sibutramine, chlorpheniramine, brompheniramine, cyproheptadine, citalopram, and paroxetine.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00711854

Locations
Switzerland
Geneva University Hospitals
Geneva, Switzerland, 1211
Sponsors and Collaborators
University Hospital, Geneva
Investigators
Principal Investigator: Stephan Harbarth, MD, MS University Hospital, Geneva
  More Information

Additional Information:
No publications provided

Responsible Party: Stephen Harbarth, Professor, University Hospital, Geneva
ClinicalTrials.gov Identifier: NCT00711854     History of Changes
Other Study ID Numbers: 08-059
Study First Received: July 3, 2008
Last Updated: August 4, 2014
Health Authority: Switzerland: Swissmedic

Keywords provided by University Hospital, Geneva:
Staphylococcal infection

Additional relevant MeSH terms:
Communicable Diseases
Infection
Staphylococcal Infections
Bacterial Infections
Gram-Positive Bacterial Infections
Linezolid
Rifampin
Sulfamethoxazole
Trimethoprim
Trimethoprim-Sulfamethoxazole Combination
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Infective Agents, Urinary
Antibiotics, Antitubercular
Antimalarials
Antiparasitic Agents
Antiprotozoal Agents
Antitubercular Agents
Enzyme Inhibitors
Folic Acid Antagonists
Leprostatic Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Protein Synthesis Inhibitors
Renal Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014