Fosfomycin Plus Imipenem for Treatment of Infective Endocarditis

Study Overview
=================
Brief Summary
-----------------
The study evaluates the efficacy and safety of fosfomycin and imipenem for the treatment of methicillin-resistant staphyloccocus aureus infective endocarditis in comparison to vancomycin, the standard therapy.

Official Title
-----------------
Evaluation of the Efficacy and Safety of Fosfomycin Plus Imipenem for the Treatment of Methicillin-resistant Staphylococcus Aureus (MRSA) Infective Endocarditis.

Conditions
-----------------
Infective Endocarditis

Intervention / Treatment
-----------------
* Drug: Fosfomycin and imipenem
* Drug: Vancomycin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Suspected methicillin-resistant staphyloccocus aureus infective endocarditis on a native valve, prosthetic valve or pacemakers´s electrode or defibrillators with definitive or probable diagnosis by the modified Duke criteria (Li J, et al. Clin Infect Dis. 2000). Patients over 18 years. Exclusion Criteria: Patients who did not sign informed consent. Patients with active consumption intravenous drug. Patients with emergent surgery criteria (<72 hours). Patients or cardiogenic shock. Patients with antibiotic active against MRSA over 72 hours or they may need another antibiotic active against MRSA than those in the study. Patients with chronic renal failure on hemodialysis who received empirical treatment with vancomycin as a single dose and have a valley ≥ 15 mcg / mL on the third day. Patients with MRSA strains resistant to fosfomycin (MIC> 64 mg / L) (<10%) or vancomycin (MIC> 2 mg / L) or with an MIC to vancomycin of 2 mg / L. Patients with any formal contraindication to be treated with study drugs Patients treated with any investigational drug within 30 days prior to entering the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>IV fosfomycin and imipenem adjusted to renal function | Drug: Fosfomycin and imipenem<br>* IV Fosfomycin 2 gr./6 hours and IV Imipenem 1 gr./6 hours adjusted acoording to renal function during 4-8 weeks<br>|
| Active Comparator: 2<br>IV Vancomycin twice a day with valley leves higher than 15 mcg/kg | Drug: Vancomycin<br>* IV Vancomycin 30 mg/kg twice a day with valley leves higher than 15 mcg/kg<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with negative blood cultures. |  | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity due to treatment |  | 20 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Infective endocarditis