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

Primary Purpose

Staph Aureus Methicillin Resistant Bacteremia

Status
Completed
Phase
Phase 3
Locations
Spain
Study Type
Interventional
Intervention
Fosfomycin 2gr/6h iv
Daptomycin 10mg/kg/24h iv
Sponsored by
Miquel Pujol
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Staph Aureus Methicillin Resistant Bacteremia focused on measuring MRSA, bacteremia, therapy

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hospital Universitari de Bellvitge
  • Hospital Parc Taulí
  • Hospital Universitari Mútua de Terrassa
  • Hospital de Terrassa
  • Hospital Universitario de Cruces
  • Hospital del Mar- Parc de Salut Mar
  • Hospital de la Santa Creu i Sant Pau
  • Hospital Vall d'Hebron
  • Hospital Clinic
  • Hospital Universitario Virgen de las Nieves
  • Hospital Universitari Arnau de Vilanova
  • Hospital Universitario Lucus Augusti
  • Hospital General Gregorio Marañon
  • Hospital Ramon y Cajal
  • Hospital Universitario 12 de Octubre
  • Complejo Asistencial Son Espases
  • Hospital Virgen Macarena
  • Hospital Universitari Joan XXIII

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Fosfomycin and Daptomycin

Daptomycin

Arm Description

fosfomycin 2gr/6h + 10mg/kg/24h iv during 14 or 28 days

daptomycin 10mg/kg/cada 24h iv during 14 or 28 days

Outcomes

Primary Outcome Measures

Therapy response
Therapy response is considered if clinical and microbiological response is achieved at week 6 after end of therapy

Secondary Outcome Measures

Mortality
Severe adverse effects
whatever
Number of persistent bacteremia
Defined as a positive blood culture on day 7 after starting the study therapy
Bacteremia recurrence
Defined as a positive blood culture to MRSA when previous ones were negative
Therapy response at end of therapy (EOT visit)
Success is considered if clinical resolution and negative blood culture at end of therapy.

Full Information

First Posted
July 2, 2013
Last Updated
January 16, 2018
Sponsor
Miquel Pujol
Collaborators
Hospital Universitari de Bellvitge
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1. Study Identification

Unique Protocol Identification Number
NCT01898338
Brief Title
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

2. Study Status

Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
December 2013 (undefined)
Primary Completion Date
January 10, 2018 (Actual)
Study Completion Date
January 10, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Miquel Pujol
Collaborators
Hospital Universitari de Bellvitge

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Staph Aureus Methicillin Resistant Bacteremia
Keywords
MRSA, bacteremia, therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
167 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Fosfomycin and Daptomycin
Arm Type
Experimental
Arm Description
fosfomycin 2gr/6h + 10mg/kg/24h iv during 14 or 28 days
Arm Title
Daptomycin
Arm Type
Active Comparator
Arm Description
daptomycin 10mg/kg/cada 24h iv during 14 or 28 days
Intervention Type
Drug
Intervention Name(s)
Fosfomycin 2gr/6h iv
Intervention Type
Drug
Intervention Name(s)
Daptomycin 10mg/kg/24h iv
Primary Outcome Measure Information:
Title
Therapy response
Description
Therapy response is considered if clinical and microbiological response is achieved at week 6 after end of therapy
Time Frame
at week 6 after end of therapy (an average of 8 to 12 weeks from the beginnig of therapy)
Secondary Outcome Measure Information:
Title
Mortality
Time Frame
participants will be followed an average of 8 to 12 weeks from the begining of therapy
Title
Severe adverse effects
Description
whatever
Time Frame
participants will be followed an average of 8 to 12 weeks from the begining of therapy
Title
Number of persistent bacteremia
Description
Defined as a positive blood culture on day 7 after starting the study therapy
Time Frame
participants will be followed an average of 8 to 12 weeks from the begining of therapy
Title
Bacteremia recurrence
Description
Defined as a positive blood culture to MRSA when previous ones were negative
Time Frame
participants will be followed an average of 8 to 12 weeks from the begining of therapy
Title
Therapy response at end of therapy (EOT visit)
Description
Success is considered if clinical resolution and negative blood culture at end of therapy.
Time Frame
at end of therapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Miquel Pujol, MD, PhD
Organizational Affiliation
(Infectious Diseases Service) Hospital Universitari de Bellvitge
Official's Role
Study Director
Facility Information:
Facility Name
Hospital Universitari de Bellvitge
City
Hospitalet de Llobregat
State/Province
Barcelona
ZIP/Postal Code
08907
Country
Spain
Facility Name
Hospital Parc Taulí
City
Sabadell
State/Province
Barcelona
ZIP/Postal Code
08208
Country
Spain
Facility Name
Hospital Universitari Mútua de Terrassa
City
Terrassa
State/Province
Barcelona
ZIP/Postal Code
08221
Country
Spain
Facility Name
Hospital de Terrassa
City
Terrassa
State/Province
Barcelona
ZIP/Postal Code
08227
Country
Spain
Facility Name
Hospital Universitario de Cruces
City
Barakaldo
ZIP/Postal Code
48903
Country
Spain
Facility Name
Hospital del Mar- Parc de Salut Mar
City
Barcelona
ZIP/Postal Code
08003
Country
Spain
Facility Name
Hospital de la Santa Creu i Sant Pau
City
Barcelona
ZIP/Postal Code
08025
Country
Spain
Facility Name
Hospital Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Clinic
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hospital Universitario Virgen de las Nieves
City
Granada
ZIP/Postal Code
18014
Country
Spain
Facility Name
Hospital Universitari Arnau de Vilanova
City
Lleida
ZIP/Postal Code
25198
Country
Spain
Facility Name
Hospital Universitario Lucus Augusti
City
Lugo
ZIP/Postal Code
27004
Country
Spain
Facility Name
Hospital General Gregorio Marañon
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Hospital Ramon y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Complejo Asistencial Son Espases
City
Palma de Mallorca
ZIP/Postal Code
07120
Country
Spain
Facility Name
Hospital Virgen Macarena
City
Sevilla
ZIP/Postal Code
41071
Country
Spain
Facility Name
Hospital Universitari Joan XXIII
City
Tarragona
ZIP/Postal Code
43007
Country
Spain

12. IPD Sharing Statement

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

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