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

MRSA Infection Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00711854
• Other study ID #: 08-059
• Status: Completed
• Phase: Phase 4
• First received: July 3, 2008
• Last updated: August 4, 2014
• Start date: January 2009
• Est. completion date: February 2014

Study information

• Verified date: August 2014
• Source: University Hospital, Geneva
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: February 2014
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Communicable Diseases
• Infection
• MRSA Infection
• Staphylococcal Infections

Intervention

Drug:
• trimethoprim-sulfamethoxazole (TMP-SMX)
TMP-SMX (160 mg TMP/ 800 mg SMX IV or PO 3x daily)
• Linezolid
Linezolid (600 mg IV or PO twice daily)
• Rifampicin
Rifampicin (600 mg IV or PO once daily)

Locations

Country	Name	City	State
Switzerland	Geneva University Hospitals	Geneva

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Geneva

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bacteriological and clinical cure		6 weeks	No
Secondary	Treatment costs		6 weeks	No