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

NCT00711854 | Completed Phase 4

• 1 other identifier: 08-059
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

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

Keywords

Staphylococcal infection

Outcome Measures

Primary Outcomes (1)

• Bacteriological and clinical cure

  6 weeks

Secondary Outcomes (1)

• Treatment costs

  6 weeks

Study Arms (2)

1

EXPERIMENTAL

trimethoprim-sulfamethoxazole (TMP-SMX) plus rifampicin

Drug: trimethoprim-sulfamethoxazole (TMP-SMX); Drug: Rifampicin

2

ACTIVE COMPARATOR

Linezolid

Drug: Linezolid

Interventions

trimethoprim-sulfamethoxazole (TMP-SMX) DRUG

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

1

Linezolid DRUG

Linezolid (600 mg IV or PO twice daily)

2

Rifampicin DRUG

Rifampicin (600 mg IV or PO once daily)

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years
• Patients with clinical signs and symptoms of MRSA-related infection
• Culture of MRSA (predominant microorganism in culture) susceptible to all of the following:
• TMP-SMX
• rifampicin
• linezolid
• Patient must give written informed consent to participate in the study.

You may not qualify if:

• Women who are pregnant or nursing
• Women who refuse to substitute oral contraception during treatment
• Known or suspected hypersensitivity to linezolid, TMP-SMX or rifampicin
• 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
• Patients with a high probability of death within the week following study entry
• Patients who, in the opinion of the investigator, cannot be relied upon for post-therapy follow-up
• 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
• Hemodialyzed patients
• History of pheochromocytoma, carcinoid syndrome, untreated hyperthyroidism, uncontrolled hypertension, or patients receiving serotonin uptake inhibitors
• Severe thrombocytopenia (\< 50.000 platelets)
• Left-sided endocarditis with a poor prognosis (patients aged over 50; cerebral embolism)
• Chronic osteomyelitis without surgical debridement; superinfected indwelling foreign body, deliberately kept in place

Sponsors & Collaborators

• University Hospital, Geneva: lead

Study Sites (1)

Geneva University Hospitals

Geneva, 1211, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 25209610 DERIVED

Related Links

• MRSA research center, Geneva University Hospitals and Medical School

MeSH Terms

Conditions

Staphylococcal Infections

Interventions

Trimethoprim, Sulfamethoxazole Drug Combination; Linezolid; Rifampin

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Trimethoprim; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Acetamides; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Stephan Harbarth, MD, MS

  University Hospital, Geneva

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 3, 2008
• First Posted: July 9, 2008
• Study Start: January 1, 2009
• Primary Completion: December 1, 2013
• Study Completion: February 1, 2014
• Last Updated: August 5, 2014

Record last verified: 2014-08

Locations

CH (1)