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Staph Aureus Methicillin Resistant BacteremiaPhase 3NCT01898338

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

A Phase 3 study testing Fosfomycin 2gr/6h iv and Daptomycin 10mg/kg/24h iv in people with Staph Aureus Methicillin Resistant Bacteremia, run by Miquel Pujol at 18 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 99 years
What is being tested?
Fosfomycin 2gr/6h iv and Daptomycin 10mg/kg/24h iv
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
167 participants
Where
18 sitesSpain
Study dates
Dec 2013to 10 Jan 2018
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

18 sites in 1 country.

18 sites in 1 country

Spain18 sites

  • Hospital Universitario de Cruces

    Barakaldo, 48903

  • Hospital del Mar- Parc de Salut Mar

    Barcelona, 08003

  • Hospital de la Santa Creu i Sant Pau

    Barcelona, 08025

  • Hospital Vall d'Hebron

    Barcelona, 08035

  • Hospital Clinic

    Barcelona, 08036

  • Hospital Universitario Virgen de las Nieves

    Granada, 18014

  • Hospital Universitari de Bellvitge

    L'Hospitalet de Llobregat, Barcelona, 08907

  • Hospital Universitari Arnau de Vilanova

    Lleida, 25198

  • Hospital Universitario Lucus Augusti

    Lugo, 27004

  • Hospital General Gregorio Marañon

    Madrid, 28007

  • Hospital Ramon y Cajal

    Madrid, 28034

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Complejo Asistencial Son Espases

    Palma de Mallorca, 07120

  • Hospital Parc Taulí

    Sabadell, Barcelona, 08208

  • Hospital Virgen Macarena

    Seville, 41071

  • Hospital Universitari Joan XXIII

    Tarragona, 43007

  • Hospital Universitari Mútua de Terrassa

    Terrassa, Barcelona, 08221

  • Hospital de Terrassa

    Terrassa, Barcelona, 08227

Other trials in Spain

About this study

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

To demonstrate that the combination of daptomycin and fosfomycin is superior to daptomycin alone in the treatment of methicillin resistant Staphylococcus aureus (MRSA) bacteremia.

Read the 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.

Being tested
Fosfomycin 2gr/6h iv, Daptomycin 10mg/kg/24h iv
Keywords
MRSA, bacteremia, therapy
Medical subject headings
Bacteremia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Fosfomycin 2gr/6h ivDrug

  • Daptomycin 10mg/kg/24h ivDrug

Study groups in NCT01898338
Study groupRoleWhat they receive
Fosfomycin and DaptomycinExperimentalfosfomycin 2gr/6h + 10mg/kg/24h iv during 14 or 28 days
Receives: Drug: Fosfomycin 2gr/6h iv; Drug: Daptomycin 10mg/kg/24h iv
DaptomycinActive comparatordaptomycin 10mg/kg/cada 24h iv during 14 or 28 days
Receives: Drug: Fosfomycin 2gr/6h iv

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Therapy response

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

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

Secondary outcomes (5)

  1. Mortality

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

  2. Severe adverse effects

    whatever

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

  3. Number of persistent bacteremia

    Defined as a positive blood culture on day 7 after starting the study therapy

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

  4. Bacteremia recurrence

    Defined as a positive blood culture to MRSA when previous ones were negative

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

  5. Therapy response at end of therapy (EOT visit)

    Success is considered if clinical resolution and negative blood culture at end of therapy.

    Measured: at end of therapy

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jul 2013 (estimated)
  2. Study startDec 2013
  3. Primary completion10 Jan 2018
  4. Study completion10 Jan 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
167 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01898338
Sponsor's protocol ID
BACSARM
Other IDs
2013-000586-37
Status last verified
Jan 2018
First submitted
2 Jul 2013
Last updated
17 Jan 2018
Results posted
No
Data monitoring committee
Yes

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

    PubMed 12491202

  • 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.

    PubMed 14530782

  • 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.

    PubMed 16914701

  • 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.

    PubMed 18782781

  • 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.

    PubMed 19254641

  • 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.

    PubMed 19915879

  • 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.

    PubMed 20186407

  • 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.

    PubMed 21217178

  • 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.

    PubMed 21549573

  • 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.

    PubMed 21612672

  • 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.

    PubMed 22644033

  • 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.

    PubMed 21923436

  • 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.

    PubMed 21862935

  • 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.

    PubMed 23331461

  • 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.

    PubMed 23089756

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Fosfomycin 2gr/6h iv and Daptomycin 10mg/kg/24h iv in people with Staph Aureus Methicillin Resistant Bacteremia, run by Miquel Pujol at 18 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Therapy response (time frame: at week 6 after end of therapy (an average of 8 to 12 weeks from the beginnig of therapy)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01898338, which also lists 18 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jan 2018.

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