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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Spanish Network for Research in Infectious Diseases
Sponsor:
Collaborator:
Hospital Universitari de Bellvitge
Information provided by (Responsible Party):
Miquel Pujol, Spanish Network for Research in Infectious Diseases
ClinicalTrials.gov Identifier:
NCT01898338
First received: July 2, 2013
Last updated: June 30, 2014
Last verified: June 2014
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Spanish Network for Research in Infectious Diseases:

Primary Outcome Measures:
  • Therapy response [ Time Frame: at week 6 after end of therapy (an average of 8 to 12 weeks from the beginnig of therapy) ] [ Designated as safety issue: No ]
    Therapy response is considered if clinical and microbiological response is achieved at week 6 after end of therapy


Secondary Outcome Measures:
  • Mortality [ Time Frame: participants will be followed an average of 8 to 12 weeks from the begining of therapy ] [ Designated as safety issue: No ]
  • Severe adverse effects [ Time Frame: participants will be followed an average of 8 to 12 weeks from the begining of therapy ] [ Designated as safety issue: Yes ]
    whatever

  • Number of persistent bacteremia [ Time Frame: participants will be followed an average of 8 to 12 weeks from the begining of therapy ] [ Designated as safety issue: No ]
    Defined as a positive blood culture on day 7 after starting the study therapy

  • Bacteremia recurrence [ Time Frame: participants will be followed an average of 8 to 12 weeks from the begining of therapy ] [ Designated as safety issue: No ]
    Defined as a positive blood culture to MRSA when previous ones were negative

  • Therapy response at end of therapy (EOT visit) [ Time Frame: at end of therapy ] [ Designated as safety issue: No ]
    Success is considered if clinical resolution and negative blood culture at end of therapy.


Estimated Enrollment: 206
Study Start Date: November 2013
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01898338

Contacts
Contact: Miquel Pujol, MD, PhD +34 93 260 73 83 ext 7383 mpujol@bellvitgehospital.cat
Contact: Evelyn Shaw, MD +34 93 260 73 83 ext 7383 evelyn.shaw@bellvitgehospital.cat

Locations
Spain
Hospital de la Santa Creu i Sant Pau Active, not recruiting
Bacelona, Barcelona, Spain, 08025
Hospital Universitari de Bellvitge Recruiting
Hospitalet de Llobregat, Barcelona, Spain, 08907
Principal Investigator: Miquel Pujol, MD, PhD         
Hospital Parc Taulí Active, not recruiting
Sabadell, Barcelona, Spain, 08208
Hospital de Terrassa Recruiting
Terrassa, Barcelona, Spain, 08227
Principal Investigator: Helena Espejo, MD         
Hospital Universitari Mútua de Terrassa Recruiting
Terrassa, Barcelona, Spain, 08221
Principal Investigator: Esther Calbo, MD, PhD         
Hospital Universitario de Cruces Active, not recruiting
Barakaldo, Spain, 48903
Hospital Clinic Active, not recruiting
Barcelona, Spain, 08036
Hospital Vall d'Hebron Recruiting
Barcelona, Spain, 08035
Principal Investigator: Carles Pigrau, MD, PhD         
Hospital del Mar- Parc de Salut Mar Active, not recruiting
Barcelona, Spain, 08003
Hospital Universitario Virgen de las Nieves Recruiting
Granada, Spain, 18014
Principal Investigator: Juan Pasquau, MD         
Hospital Universitari Arnau de Vilanova Recruiting
Lleida, Spain, 25198
Principal Investigator: Fernando Barcenilla, MD         
Hospital Universitario Lucus Augusti Not yet recruiting
Lugo, Spain, 27004
Principal Investigator: M Jose Garcia-Pais, MD         
Hospital General Gregorio Marañon Recruiting
Madrid, Spain, 28007
Principal Investigator: Belen Padilla, MD         
Hospital Ramon y Cajal Recruiting
Madrid, Spain, 28034
Principal Investigator: Vicente Pintado, MD         
Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain, 28041
Principal Investigator: Ana Garcia-Reyne, MD         
Complejo Asistencial Son Espases Recruiting
Palma de Mallorca, Spain, 07120
Principal Investigator: Javier Murillas, MD, PhD         
Hospital Virgen Macarena Recruiting
Sevilla, Spain, 41071
Principal Investigator: Jesús Rodriguez-Baño, MD, PhD         
Hospital Universitari Joan XXIII Recruiting
Tarragona, Spain, 43007
Principal Investigator: Graciano Garcia Pardo, MD         
Hospital Universitari i Politèncic La Fe Active, not recruiting
Valencia, Spain, 46026
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:

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
Study First Received: July 2, 2013
Last Updated: June 30, 2014
Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by 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
Fosfomycin
Daptomycin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 14, 2014