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Efficacy of Daptomycin Plus Fosfomycin Versus Daptomycin for Treatment of MRSA Bacteremia

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ClinicalTrials.gov Identifier: NCT01898338
Recruitment Status : Completed
First Posted : July 12, 2013
Last Update Posted : January 17, 2018
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
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.

Condition or disease Intervention/treatment Phase
Staph Aureus Methicillin Resistant Bacteremia Drug: Fosfomycin 2gr/6h iv Drug: Daptomycin 10mg/kg/24h iv Phase 3

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.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 167 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : December 2013
Primary Completion Date : January 10, 2018
Study Completion Date : January 10, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: MRSA
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Fosfomycin and Daptomycin
fosfomycin 2gr/6h + 10mg/kg/24h iv during 14 or 28 days
Drug: Fosfomycin 2gr/6h iv Drug: Daptomycin 10mg/kg/24h iv
Active Comparator: Daptomycin
daptomycin 10mg/kg/cada 24h iv during 14 or 28 days
Drug: Fosfomycin 2gr/6h iv


Outcome Measures

Primary Outcome Measures :
  1. Therapy response [ Time Frame: at week 6 after end of therapy (an average of 8 to 12 weeks from the beginnig of therapy) ]
    Therapy response is considered if clinical and microbiological response is achieved at week 6 after end of therapy


Secondary Outcome Measures :
  1. Mortality [ Time Frame: participants will be followed an average of 8 to 12 weeks from the begining of therapy ]
  2. Severe adverse effects [ Time Frame: participants will be followed an average of 8 to 12 weeks from the begining of therapy ]
    whatever

  3. Number of persistent bacteremia [ Time Frame: participants will be followed an average of 8 to 12 weeks from the begining of therapy ]
    Defined as a positive blood culture on day 7 after starting the study therapy

  4. Bacteremia recurrence [ Time Frame: participants will be followed an average of 8 to 12 weeks from the begining of therapy ]
    Defined as a positive blood culture to MRSA when previous ones were negative

  5. Therapy response at end of therapy (EOT visit) [ Time Frame: at end of therapy ]
    Success is considered if clinical resolution and negative blood culture at end of therapy.


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01898338


Locations
Spain
Hospital Universitari de Bellvitge
Hospitalet de Llobregat, Barcelona, Spain, 08907
Hospital Parc Taulí
Sabadell, Barcelona, Spain, 08208
Hospital Universitari Mútua de Terrassa
Terrassa, Barcelona, Spain, 08221
Hospital de Terrassa
Terrassa, Barcelona, Spain, 08227
Hospital Universitario de Cruces
Barakaldo, Spain, 48903
Hospital del Mar- Parc de Salut Mar
Barcelona, Spain, 08003
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain, 08025
Hospital Vall d'Hebron
Barcelona, Spain, 08035
Hospital Clinic
Barcelona, Spain, 08036
Hospital Universitario Virgen de las Nieves
Granada, Spain, 18014
Hospital Universitari Arnau de Vilanova
Lleida, Spain, 25198
Hospital Universitario Lucus Augusti
Lugo, Spain, 27004
Hospital General Gregorio Marañon
Madrid, Spain, 28007
Hospital Ramon y Cajal
Madrid, Spain, 28034
Hospital Universitario 12 de Octubre
Madrid, Spain, 28041
Complejo Asistencial Son Espases
Palma de Mallorca, Spain, 07120
Hospital Virgen Macarena
Sevilla, Spain, 41071
Hospital Universitari Joan XXIII
Tarragona, Spain, 43007
Sponsors and Collaborators
Miquel Pujol
Hospital Universitari de Bellvitge
Investigators
Study Director: Miquel Pujol, MD, PhD (Infectious Diseases Service) Hospital Universitari de Bellvitge
More Information

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Miquel Pujol, MD and PhD, Spanish Network for Research in Infectious Diseases
ClinicalTrials.gov Identifier: NCT01898338     History of Changes
Other Study ID Numbers: BACSARM
2013-000586-37 ( EudraCT Number )
First Posted: July 12, 2013    Key Record Dates
Last Update Posted: January 17, 2018
Last Verified: January 2018

Keywords provided by Miquel Pujol, Spanish Network for Research in Infectious Diseases:
MRSA
bacteremia
therapy

Additional relevant MeSH terms:
Bacteremia
Bacterial Infections
Sepsis
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Daptomycin
Fosfomycin
Anti-Bacterial Agents
Anti-Infective Agents