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

NCT ID: NCT00711854

Last Updated: 2014-08-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2014-02-28

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.

Conditions

MRSA Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

trimethoprim-sulfamethoxazole (TMP-SMX) plus rifampicin

Group Type: EXPERIMENTAL

trimethoprim-sulfamethoxazole (TMP-SMX)

Intervention Type: DRUG

TMP-SMX (160 mg TMP/ 800 mg SMX IV or PO 3x daily)

Rifampicin

Intervention Type: DRUG

Rifampicin (600 mg IV or PO once daily)

2

Linezolid

Group Type: ACTIVE_COMPARATOR

Linezolid

Intervention Type: DRUG

Linezolid (600 mg IV or PO twice daily)

Interventions

trimethoprim-sulfamethoxazole (TMP-SMX)

TMP-SMX (160 mg TMP/ 800 mg SMX IV or PO 3x daily)

Intervention Type: DRUG

Linezolid

Linezolid (600 mg IV or PO twice daily)

Intervention Type: DRUG

Rifampicin

Rifampicin (600 mg IV or PO once daily)

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Geneva

OTHER

Sponsor Role: lead

Responsible Party

Stephen Harbarth

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Stephan Harbarth, MD, MS

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Geneva

Locations

Geneva University Hospitals

Geneva, , Switzerland

Countries

Switzerland

References

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.

Reference Type: DERIVED

PMID: 25209610 (View on PubMed)

Related Links

http://medweb1.unige.ch/recherche/groupes/b_donnees/sujet_330_1.html

MRSA research center, Geneva University Hospitals and Medical School

Other Identifiers

08-059

Identifier Type: -

Identifier Source: org_study_id