Daptomycin plus fosfomycin versus daptomycin monotherapy in treating MRSA: protocol of a multicentre, randomised, phase III trial.

January 26, 2017 at 3:39 pm

BMJ Open. 2015 Mar 11;5(3):e006723.

Shaw E1, Miró JM2, Puig-Asensio M3, Pigrau C3, Barcenilla F4, Murillas J5, Garcia-Pardo G6, Espejo E7, Padilla B8, Garcia-Reyne A9, Pasquau J10, Rodriguez-Baño J11, López-Contreras J12, Montero M13, de la Calle C2, Pintado V14, Calbo E15, Gasch O16, Montejo M17, Salavert M18, Garcia-Pais MJ19, Carratalà J1, Pujol M1; Spanish Network for Research in Infectious Diseases (REIPI RD12/0015); Instituto de Salud Carlos III, Madrid, Spain; GEIH (Hospital Infection Study Group).

Collaborators (47)

Author information

1Hospital Universitari de Bellvitge-IDIBELL, Hospitalet de Llobregat, Barcelona, Spain.

2Hospital Universitari Clínic-IDIBAPS, Barcelona, Spain.

3Hospital Universitari Vall d’Hebron, Barcelona, Spain.

4Hospital Universitari Arnau de Vilanova, Lleida, Spain.

5Hospital Universitari Son Espases, Mallorca, Spain.

6Hospital Universitari Joan XXIII, Tarragona, Spain.

7Hospital Universitari de Terrassa, Terrassa, Barcelona, Spain.

8Hospital Universitario Gregorio Marañon, Madrid, Spain.

9Hospital Universitario 12 de Octubre, Madrid, Spain.

10Hospital Universitario Virgen de las Nieves, Granada, Spain.

11Hospital Universitario Virgen Macarena, Sevilla, Spain.

12Hospital Universitari Santa Creu i Sant Pau, Barcelona, Spain.

13Hospital Universitari Parc de Salut Mar, Barcelona, Spain.

14Hospital Universitario Ramón y Cajal, Madrid, Spain.

15Hospital Universitari Mutúa de Terrassa, Barcelona, Spain.

16Corporació Sanitaria Parc Taulí, Sabadell, Barcelona, Spain.

17Hospital Universitario de Cruces, Barakaldo, Spain.

18Hospital Universitari i Politècnic la Fe, Valencia, Spain.

19Hospital Universitario Lucus Augusti, Lugo, Spain.

Abstract

INTRODUCTION:

Despite the availability of new antibiotics such as daptomycin, methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia continues to be associated with high clinical failure rates. Combination therapy has been proposed as an alternative to improve outcomes but there is a lack of clinical studies. The study aims to demonstrate that combination of daptomycin plus fosfomycin achieves higher clinical success rates in the treatment of MRSA bacteraemia than daptomycin alone.

METHODS AND ANALYSIS:

A multicentre open-label, randomised phase III study. Adult patients hospitalised with MRSA bacteraemia will be randomly assigned (1:1) to group 1: daptomycin 10 mg/kg/24 h intravenous; or group 2: daptomycin 10 mg/kg/24 h intravenous plus fosfomycin 2 gr/6 g intravenous. The main outcome will be treatment response at week 6 after stopping therapy (test-of-cure (TOC) visit). This is a composite variable with two values: Treatment success: resolution of clinical signs and symptoms (clinical success) and negative blood cultures (microbiological success) at the TOC visit. Treatment failure: if any of the following conditions apply: (1) lack of clinical improvement at 72 h or more after starting therapy; (2) persistent bacteraemia (positive blood cultures on day 7); (3) therapy is discontinued early due to adverse effects or for some other reason based on clinical judgement; (4) relapse of MRSA bacteraemia before the TOC visit; (5) death for any reason before the TOC visit. Assuming a 60% cure rate with daptomycin and a 20% difference in cure rates between the two groups, 103 patients will be needed for each group (α:0.05, ß: 0.2). Statistical analysis will be based on intention to treat, as well as per protocol and safety analysis.

ETHICS AND DISSEMINATION:

The protocol was approved by the Spanish Medicines and Healthcare Products Regulatory Agency (AEMPS). The sponsor commits itself to publishing the data in first quartile peer-review journals within 12 months of the completion of the study.

TRIAL REGISTRATION NUMBER: NCT01898338.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4360784/pdf/bmjopen-2014-006723.pdf

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Entry filed under: Antimicrobianos, Bacterias, Bacteriemias, Biología Molecular, Epidemiología, Metodos diagnosticos, Resistencia bacteriana, REVIEWS, Sepsis, Update.

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