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

NCT01898338 | Completed Phase 3 DMC

• 2 other identifiers: BACSARM2013-000586-37
• Study Type: interventional
• Target: 167
• Locations: 1 country
• Sites: 18

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.

Conditions

Staph Aureus Methicillin Resistant Bacteremia

Keywords

MRSA; bacteremia; therapy

Outcome Measures

Primary Outcomes (1)

• Therapy response

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

  at week 6 after end of therapy (an average of 8 to 12 weeks from the beginnig of therapy)

Secondary Outcomes (5)

• Mortality

  participants will be followed an average of 8 to 12 weeks from the begining of therapy

• Severe adverse effects

  participants will be followed an average of 8 to 12 weeks from the begining of therapy

• Number of persistent bacteremia

  participants will be followed an average of 8 to 12 weeks from the begining of therapy

• Bacteremia recurrence

  participants will be followed an average of 8 to 12 weeks from the begining of therapy

• Therapy response at end of therapy (EOT visit)

  at end of therapy

Study Arms (2)

Fosfomycin and Daptomycin

EXPERIMENTAL

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

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

Daptomycin

ACTIVE COMPARATOR

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

Drug: Fosfomycin 2gr/6h iv

Interventions

Fosfomycin 2gr/6h iv DRUG

Daptomycin; Fosfomycin and Daptomycin

Daptomycin 10mg/kg/24h iv DRUG

Fosfomycin and Daptomycin

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Polymicrobial bacteremia
• Pneumonia associated to the bacteremia
• Severe clinical status with expected survival of less than 24 hours
• Allergy to daptomycin or fosfomycin
• 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

Sponsors & Collaborators

• Miquel Pujol: lead
• Hospital Universitari de Bellvitge: collaborator

Study Sites (18)

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Hospital Parc Taulí

Sabadell, Barcelona, 08208, Spain

Location

Hospital Universitari Mútua de Terrassa

Terrassa, Barcelona, 08221, Spain

Location

Hospital de Terrassa

Terrassa, Barcelona, 08227, Spain

Location

Hospital Universitario de Cruces

Barakaldo, 48903, Spain

Location

Hospital del Mar- Parc de Salut Mar

Barcelona, 08003, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic

Barcelona, 08036, Spain

Location

Hospital Universitario Virgen de las Nieves

Granada, 18014, Spain

Location

Hospital Universitari Arnau de Vilanova

Lleida, 25198, Spain

Location

Hospital Universitario Lucus Augusti

Lugo, 27004, Spain

Location

Hospital General Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Complejo Asistencial Son Espases

Palma de Mallorca, 07120, Spain

Location

Hospital Virgen Macarena

Seville, 41071, Spain

Location

Hospital Universitari Joan XXIII

Tarragona, 43007, Spain

Location

Related Publications (18)

• 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. doi: 10.1086/345476. Epub 2002 Dec 13.

  PMID: 12491202 BACKGROUND

• 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. doi: 10.1097/01.md.0000091184.93122.09.

  PMID: 14530782 BACKGROUND

• 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, Fatkenheuer 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. doi: 10.1056/NEJMoa053783.

  PMID: 16914701 BACKGROUND

• 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.

  PMID: 18782781 BACKGROUND

• Gudiol F, Aguado JM, Pascual A, Pujol M, Almirante B, Miro JM, Cercenado E, Dominguez Mde L, Soriano A, Rodriguez-Bano J, Valles J, Palomar M, Tornos P, Bouza E; Sociedad Espanola de Enfermedades Infecciosas y Microbiologia Clinica. [Consensus document for the treatment of bacteremia and endocarditis caused by methicillin-resistent Staphylococcus aureus. Sociedad Espanola de Enfermedades Infecciosas y Microbiologia Clinica]. Enferm Infecc Microbiol Clin. 2009 Feb;27(2):105-15. doi: 10.1016/j.eimc.2008.09.003. Epub 2009 Feb 11. Spanish.

  PMID: 19254641 BACKGROUND

• 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.

  PMID: 19915879 BACKGROUND

• 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.

  PMID: 20186407 BACKGROUND

• 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.

  PMID: 21217178 BACKGROUND

• 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.

  PMID: 21549573 BACKGROUND

• 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.

  PMID: 21612672 BACKGROUND

• Miro JM, Entenza JM, Del Rio A, Velasco M, Castaneda X, Garcia de la Maria C, Giddey M, Armero Y, Pericas 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. doi: 10.1128/AAC.06449-11. Epub 2012 May 29.

  PMID: 22644033 BACKGROUND

• 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.

  PMID: 21923436 BACKGROUND

• Gasch O, Ayats J, Angeles Dominguez M, Tubau F, Linares J, Pena C, Grau I, Pallares 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):319-327. doi: 10.1097/MD.0b013e31822f0b54.

  PMID: 21862935 BACKGROUND

• 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-Bano 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.

  PMID: 23331461 BACKGROUND

• Garrigos 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.

  PMID: 23089756 BACKGROUND

• 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.

  PMID: 23379510 BACKGROUND

• Pujol M, Miro JM, Shaw E, Aguado JM, San-Juan R, Puig-Asensio M, Pigrau C, Calbo E, Montejo M, Rodriguez-Alvarez R, Garcia-Pais MJ, Pintado V, Escudero-Sanchez R, Lopez-Contreras J, Morata L, Montero M, Andres M, Pasquau J, Arenas MD, Padilla B, Murillas J, Jover-Saenz A, Lopez-Cortes LE, Garcia-Pardo G, Gasch O, Videla S, Hereu P, Tebe C, Pallares N, Sanllorente M, Dominguez MA, Camara J, Ferrer A, Padulles A, Cuervo G, Carratala J; MRSA Bacteremia (BACSARM) Trial Investigators. Daptomycin Plus Fosfomycin Versus Daptomycin Alone for Methicillin-resistant Staphylococcus aureus Bacteremia and Endocarditis: A Randomized Clinical Trial. Clin Infect Dis. 2021 May 4;72(9):1517-1525. doi: 10.1093/cid/ciaa1081.

  PMID: 32725216 DERIVED

• Shaw E, Miro JM, Puig-Asensio M, Pigrau C, Barcenilla F, Murillas J, Garcia-Pardo G, Espejo E, Padilla B, Garcia-Reyne A, Pasquau J, Rodriguez-Bano J, Lopez-Contreras J, Montero M, de la Calle C, Pintado V, Calbo E, Gasch O, Montejo M, Salavert M, Garcia-Pais MJ, Carratala J, Pujol M; Spanish Network for Research in Infectious Diseases (REIPI RD12/0015); Instituto de Salud Carlos III, Madrid, Spain; GEIH (Hospital Infection Study Group). Daptomycin plus fosfomycin versus daptomycin monotherapy in treating MRSA: protocol of a multicentre, randomised, phase III trial. BMJ Open. 2015 Mar 11;5(3):e006723. doi: 10.1136/bmjopen-2014-006723.

  PMID: 25762232 DERIVED

MeSH Terms

Conditions

Bacteremia

Interventions

Daptomycin

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Miquel Pujol, MD, PhD

  (Infectious Diseases Service) Hospital Universitari de Bellvitge

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD and PhD

Study Record Dates

• First Submitted: July 2, 2013
• First Posted: July 12, 2013
• Study Start: December 1, 2013
• Primary Completion: January 10, 2018
• Study Completion: January 10, 2018
• Last Updated: January 17, 2018

Record last verified: 2018-01

Locations

ES (18)