Clinical trial NCT00711854: 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
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: MRSA Infection
Keywords: Staphylococcal infection
Lead sponsor: University Hospital, Geneva
Sponsor class: OTHER
First posted: 2008-07-09
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Bacteriological and clinical cure
timeFrame: 6 weeks
Secondary outcomes:
measure: Treatment costs
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Geneva
country: Switzerland
facility: Geneva University Hospitals
Study officials:
affiliation: University Hospital, Geneva
name: Stephan Harbarth, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Harbarth S, von Dach E, Pagani L, Macedo-Vinas M, Huttner B, Olearo F, Emonet S, Uckay I. Randomized non-inferiority trial to compare trimethoprim/sulfamethoxazole plus rifampicin versus linezolid for the treatment of MRSA infection. J Antimicrob Chemother. 2015 Jan;70(1):264-72. doi: 10.1093/jac/dku352. Epub 2014 Sep 10.