DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



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

Information source: Spanish Network for Research in Infectious Diseases
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Staph Aureus Methicillin Resistant Bacteremia

Intervention: Fosfomycin 2gr/6h iv (Drug); Daptomycin 10mg/kg/24h iv (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Miquel Pujol

Official(s) and/or principal investigator(s):
Miquel Pujol, MD, PhD, Study Director, Affiliation: (Infectious Diseases Service) Hospital Universitari de Bellvitge

Overall contact:
Miquel Pujol, MD, PhD, Phone: +34 93 260 73 83, Ext: 7383, Email: mpujol@bellvitgehospital.cat

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.

Clinical Details

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 design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Therapy response

Secondary outcome:

Mortality

Severe adverse effects

Number of persistent bacteremia

Bacteremia recurrence

Therapy response at end of therapy (EOT visit)

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

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Locations and Contacts

Miquel Pujol, MD, PhD, Phone: +34 93 260 73 83, Ext: 7383, Email: mpujol@bellvitgehospital.cat

Hospital Universitario de Cruces, Barakaldo 48903, Spain; Recruiting
Miguel Montejo, MD, Principal Investigator

Hospital Clinic, Barcelona 08036, Spain; Recruiting
Alex Soriano, MD, PhD, Principal Investigator

Hospital del Mar- Parc de Salut Mar, Barcelona 08003, Spain; Recruiting
Milagro Montero, MD, PhD, Principal Investigator

Hospital Vall d'Hebron, Barcelona 08035, Spain; Recruiting
Carles Pigrau, MD, PhD, Principal Investigator

Hospital Universitario Virgen de las Nieves, Granada 18014, Spain; Recruiting
Juan Pasquau, MD, Principal Investigator

Hospital Universitari Arnau de Vilanova, Lleida 25198, Spain; Recruiting
Fernando Barcenilla, MD, Principal Investigator

Hospital Universitario Lucus Augusti, Lugo 27004, Spain; Active, not recruiting

Hospital General Gregorio Marañon, Madrid 28007, Spain; Recruiting
Belen Padilla, MD, Principal Investigator

Hospital Ramon y Cajal, Madrid 28034, Spain; Recruiting
Vicente Pintado, MD, Principal Investigator

Hospital Universitario 12 de Octubre, Madrid 28041, Spain; Recruiting
Ana Garcia-Reyne, MD, Principal Investigator

Complejo Asistencial Son Espases, Palma de Mallorca 07120, Spain; Recruiting
Javier Murillas, MD, PhD, Principal Investigator

Hospital Virgen Macarena, Sevilla 41071, Spain; Recruiting
Jesús Rodriguez-Baño, MD, PhD, Principal Investigator

Hospital Universitari Joan XXIII, Tarragona 43007, Spain; Recruiting
Graciano Garcia Pardo, MD, Principal Investigator

Hospital Universitari i Politèncic La Fe, Valencia 46026, Spain; Active, not recruiting

Hospital de la Santa Creu i Sant Pau, Bacelona, Barcelona 08025, Spain; Recruiting
Joaquin Lopez-Contreras, MD, Principal Investigator

Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona 08907, Spain; Recruiting
Miquel Pujol, MD, PhD, Principal Investigator

Hospital Parc Taulí, Sabadell, Barcelona 08208, Spain; Recruiting
Oriol Gasch, MD, Principal Investigator

Hospital de Terrassa, Terrassa, Barcelona 08227, Spain; Recruiting
Helena Espejo, MD, Principal Investigator

Hospital Universitari Mútua de Terrassa, Terrassa, Barcelona 08221, Spain; Recruiting
Esther Calbo, MD, PhD, Principal Investigator

Additional Information

Related publications:

Cosgrove SE, Sakoulas G, Perencevich EN, Schwaber MJ, Karchmer AW, Carmeli Y. Comparison of mortality associated with methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteremia: a meta-analysis. Clin Infect Dis. 2003 Jan 1;36(1):53-9. Epub 2002 Dec 13.

Chang FY, Peacock JE Jr, Musher DM, Triplett P, MacDonald BB, Mylotte JM, O'Donnell A, Wagener MM, Yu VL. Staphylococcus aureus bacteremia: recurrence and the impact of antibiotic treatment in a prospective multicenter study. Medicine (Baltimore). 2003 Sep;82(5):333-9.

Fowler VG Jr, Boucher HW, Corey GR, Abrutyn E, Karchmer AW, Rupp ME, Levine DP, Chambers HF, Tally FP, Vigliani GA, Cabell CH, Link AS, DeMeyer I, Filler SG, Zervos M, Cook P, Parsonnet J, Bernstein JM, Price CS, Forrest GN, Fätkenheuer G, Gareca M, Rehm SJ, Brodt HR, Tice A, Cosgrove SE; S. aureus Endocarditis and Bacteremia Study Group. Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med. 2006 Aug 17;355(7):653-65.

Rehm SJ, Boucher H, Levine D, Campion M, Eisenstein BI, Vigliani GA, Corey GR, Abrutyn E. Daptomycin versus vancomycin plus gentamicin for treatment of bacteraemia and endocarditis due to Staphylococcus aureus: subset analysis of patients infected with methicillin-resistant isolates. J Antimicrob Chemother. 2008 Dec;62(6):1413-21. doi: 10.1093/jac/dkn372. Epub 2008 Sep 8.

Gudiol F, Aguado JM, Pascual A, Pujol M, Almirante B, Miró JM, Cercenado E, Domínguez Mde L, Soriano A, Rodríguez-Baño J, Vallés J, Palomar M, Tornos P, Bouza E; Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. [Consensus document for the treatment of bacteremia and endocarditis caused by methicillin-resistent Staphylococcus aureus. Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica]. Enferm Infecc Microbiol Clin. 2009 Feb;27(2):105-15. doi: 10.1016/j.eimc.2008.09.003. Epub 2009 Feb 11. Review. Spanish.

Popovic M, Steinort D, Pillai S, Joukhadar C. Fosfomycin: an old, new friend? Eur J Clin Microbiol Infect Dis. 2010 Feb;29(2):127-42. doi: 10.1007/s10096-009-0833-2. Epub 2009 Nov 14. Review.

Kastoris AC, Rafailidis PI, Vouloumanou EK, Gkegkes ID, Falagas ME. Synergy of fosfomycin with other antibiotics for Gram-positive and Gram-negative bacteria. Eur J Clin Pharmacol. 2010 Apr;66(4):359-68. doi: 10.1007/s00228-010-0794-5. Epub 2010 Feb 26.

Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, Kaplan SL, Karchmer AW, Levine DP, Murray BE, J Rybak M, Talan DA, Chambers HF. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children: executive summary. Clin Infect Dis. 2011 Feb 1;52(3):285-92. doi: 10.1093/cid/cir034.

Wu G, Abraham T, Rapp J, Vastey F, Saad N, Balmir E. Daptomycin: evaluation of a high-dose treatment strategy. Int J Antimicrob Agents. 2011 Sep;38(3):192-6. doi: 10.1016/j.ijantimicag.2011.03.006. Epub 2011 May 6. Review.

Chen LY, Huang CH, Kuo SC, Hsiao CY, Lin ML, Wang FD, Fung CP. High-dose daptomycin and fosfomycin treatment of a patient with endocarditis caused by daptomycin-nonsusceptible Staphylococcus aureus: case report. BMC Infect Dis. 2011 May 26;11:152. doi: 10.1186/1471-2334-11-152.

Miró JM, Entenza JM, Del Río A, Velasco M, Castañeda X, Garcia de la Mària C, Giddey M, Armero Y, Pericàs JM, Cervera C, Mestres CA, Almela M, Falces C, Marco F, Moreillon P, Moreno A; Hospital Clinic Experimental Endocarditis Study Group. High-dose daptomycin plus fosfomycin is safe and effective in treating methicillin-susceptible and methicillin-resistant Staphylococcus aureus endocarditis. Antimicrob Agents Chemother. 2012 Aug;56(8):4511-5. Epub 2012 May 29.

Kullar R, Davis SL, Levine DP, Zhao JJ, Crank CW, Segreti J, Sakoulas G, Cosgrove SE, Rybak MJ. High-dose daptomycin for treatment of complicated gram-positive infections: a large, multicenter, retrospective study. Pharmacotherapy. 2011 Jun;31(6):527-36. doi: 10.1592/phco.31.6.527.

Gasch O, Ayats J, Angeles Dominguez M, Tubau F, Liñares J, Peña C, Grau I, Pallarés R, Gudiol F, Ariza J, Pujol M. Epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection: secular trends over 19 years at a university hospital. Medicine (Baltimore). 2011 Sep;90(5):319-27. doi: 10.1097/MD.0b013e31822f0b54.

Gasch O, Camoez M, Dominguez MA, Padilla B, Pintado V, Almirante B, Molina J, Lopez-Medrano F, Ruiz E, Martinez JA, Bereciartua E, Rodriguez-Lopez F, Fernandez-Mazarrasa C, Goenaga MA, Benito N, Rodriguez-Baño J, Espejo E, Pujol M; REIPI/GEIH Study Groups. Predictive factors for mortality in patients with methicillin-resistant Staphylococcus aureus bloodstream infection: impact on outcome of host, microorganism and therapy. Clin Microbiol Infect. 2013 Nov;19(11):1049-57. doi: 10.1111/1469-0691.12108. Epub 2013 Jan 17.

Garrigós C, Murillo O, Lora-Tamayo J, Verdaguer R, Tubau F, Cabellos C, Cabo J, Ariza J. Fosfomycin-daptomycin and other fosfomycin combinations as alternative therapies in experimental foreign-body infection by methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2013 Jan;57(1):606-10. doi: 10.1128/AAC.01570-12. Epub 2012 Oct 22.

Lai CC, Sheng WH, Wang JT, Cheng A, Chuang YC, Chen YC, Chang SC. Safety and efficacy of high-dose daptomycin as salvage therapy for severe gram-positive bacterial sepsis in hospitalized adult patients. BMC Infect Dis. 2013 Feb 4;13:66. doi: 10.1186/1471-2334-13-66.

Starting date: December 2013
Last updated: April 13, 2015

Page last updated: August 23, 2015

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017