Clinical trial NCT01898338: Efficacy of Daptomycin Plus Fosfomycin Versus Daptomycin for Treatment of MRSA Bacteremia
Official title: Randomized Multicenter Study to Assess Efficacy of Daptomycin Plus Fosfomycin Versus Daptomycin Monotherapy for Treatment of Methicillin Resistant Staphylococcus Aureus Bacteremia in Hospitalized Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Staph Aureus Methicillin Resistant Bacteremia
Keywords: MRSA
bacteremia
therapy
Lead sponsor: Spanish Network for Research in Infectious Diseases
Sponsor class: OTHER
Collaborators: name: Hospital Universitari de Bellvitge
First posted: 2013-07-12
Enrollment: 167
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To demonstrate that the combination of daptomycin and fosfomycin is superior to daptomycin alone in the treatment of methicillin resistant Staphylococcus aureus (MRSA) bacteremia.

Detailed description: The mortality associated to MRSA bacteremia remains higher than 30% of episodes despite the availability of new antibiotics. Objective: To demonstrate that the combination of daptomycin and fosfomycin is superior to daptomycin alone in the treatment of methicillin resistant Staphylococcus aureus (MRSA) bacteremia. Design: Randomized, open-label and multicenter study. Intervention: Patients with MRSA bacteremia will be randomized (1:1) in Group 1: daptomycin 10mg/Kg/24h intravenous (iv) and Group 2: daptomycin 10 mg/kg/24 iv plus fosfomycin and 2g/6h iv. Duration of therapy will be 10-14 days for uncomplicated bacteremia and up to 42 days for complicated bacteremia. Follow up: There will be a clinical and microbiological evaluation at baseline, during treatment and at week 6 after the end of therapy (test of cure visit, TOC). Complicated bacteremia was considered if: a) persistence of a positive blood culture at 72-96 h from the start of antibiotic, b) evidence of spread of infection (metastatic infection) c) infection involving a non-removable device in less than 4 days. Sample size: Assuming 60% cure rate with daptomycin and a 20% difference in cure rates between both groups, we estimated that 103 patients will be needed for each group (α:0.05, ß: 0.2). Main endpoint: clinical and microbiological response at the TOC visit. Treatment success was defined as the resolution of clinical signs and symptoms and negative blood culture. Treatment failure was defined if any of the following situations: a) lack of clinical response at 72 h or more after initiation of the study therapy b) persistent bacteremia (positive blood culture on day 7 after randomization), c) withdrawal of treatment due to adverse effects or for any other reason based on clinical judgment. d) relapse of MRSA bacteremia before the TOC visit e) death for any reason before the TOC visit. Secondary endpoints: evaluation in both groups of clinical and microbiological response at end of therapy (EOT visit); mortality at EOT and TOC visit; persistent MRSA bacteremia; recurrence of MRSA bacteremia (positive blood culture when previous ones were negative); emergence of daptomycin or fosfomycin resistance and severe adverse effects.

Eligibility criteria: Inclusion Criteria:

* Patients with at least 1 positive blood culture to MRSA within 72h up to randomization
* Adult patients, equal or older than 18 years old
* Signed informed consent
* Mandatory use of contraception methods for fertile women during the study period and for 6 months after stopping antibiotic therapy

Exclusion Criteria:

* Polymicrobial bacteremia
* Pneumonia associated to the bacteremia
* Severe clinical status with expected survival of less than 24 hours
* Allergy to daptomycin or fosfomycin
* A positive pregnancy test at the time of inclusion
* Any clinical condition that requires additional antibiotic therapy with microbiological activity against MRSA
* Patient already included in another clinical trial
* Prior history of eosinophilic pneumonia

Primary outcomes:
measure: Therapy response
timeFrame: at week 6 after end of therapy (an average of 8 to 12 weeks from the beginnig of therapy)
Secondary outcomes:
measure: Mortality
timeFrame: participants will be followed an average of 8 to 12 weeks from the begining of therapy
measure: Severe adverse effects
timeFrame: participants will be followed an average of 8 to 12 weeks from the begining of therapy
measure: Number of persistent bacteremia
timeFrame: participants will be followed an average of 8 to 12 weeks from the begining of therapy
measure: Bacteremia recurrence
timeFrame: participants will be followed an average of 8 to 12 weeks from the begining of therapy
measure: Therapy response at end of therapy (EOT visit)
timeFrame: at end of therapy
Other outcomes:
Locations:
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge
state: Barcelona
city: Sabadell
country: Spain
facility: Hospital Parc Taulí
state: Barcelona
city: Terrassa
country: Spain
facility: Hospital Universitari Mútua de Terrassa
state: Barcelona
city: Terrassa
country: Spain
facility: Hospital de Terrassa
state: Barcelona
city: Barakaldo
country: Spain
facility: Hospital Universitario de Cruces
city: Barcelona
country: Spain
facility: Hospital del Mar- Parc de Salut Mar
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves
city: Lleida
country: Spain
facility: Hospital Universitari Arnau de Vilanova
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti
city: Madrid
country: Spain
facility: Hospital General Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Palma de Mallorca
country: Spain
facility: Complejo Asistencial Son Espases
city: Sevilla
country: Spain
facility: Hospital Virgen Macarena
city: Tarragona
country: Spain
facility: Hospital Universitari Joan XXIII
Study officials:
affiliation: (Infectious Diseases Service) Hospital Universitari de Bellvitge
name: Miquel Pujol, MD, PhD
role: STUDY_DIRECTOR
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