Fosfomycin Plus Imipenem for Treatment of Infective Endocarditis

• ClinicalTrials.gov Identifier: NCT00871104
• Recruitment Status: Completed
• First Posted: March 30, 2009
• Last Update Posted: March 8, 2018
• Sponsor: Juan A. Arnaiz
• Information provided by (Responsible Party): Juan A. Arnaiz, Hospital Clinic of Barcelona

Tracking Information

• First Submitted Date: March 27, 2009
• First Posted Date: March 30, 2009
• Last Update Posted Date: March 8, 2018
• Study Start Date: July 2009
• Actual Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: March 27, 2009): Proportion of patients with negative blood cultures. [ Time Frame: 7 days ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: March 27, 2009): Toxicity due to treatment [ Time Frame: 20 weeks ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Fosfomycin Plus Imipenem for Treatment of Infective Endocarditis
• Official Title: Evaluation of the Efficacy and Safety of Fosfomycin Plus Imipenem for the Treatment of Methicillin-resistant Staphylococcus Aureus (MRSA) Infective Endocarditis.
• Brief Summary: The study evaluates the efficacy and safety of fosfomycin and imipenem for the treatment of methicillin-resistant staphyloccocus aureus infective endocarditis in comparison to vancomycin, the standard therapy.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Infective Endocarditis

Intervention

• Drug: Fosfomycin and imipenem
  IV Fosfomycin 2 gr./6 hours and IV Imipenem 1 gr./6 hours adjusted acoording to renal function during 4-8 weeks
• Drug: Vancomycin
  IV Vancomycin 30 mg/kg twice a day with valley leves higher than 15 mcg/kg

Study Arms

• Experimental: 1
  IV fosfomycin and imipenem adjusted to renal function
  Intervention: Drug: Fosfomycin and imipenem
• Active Comparator: 2
  IV Vancomycin twice a day with valley leves higher than 15 mcg/kg
  Intervention: Drug: Vancomycin

Publications *

• Pericàs JM, Ambrosioni J, Muñoz P, de Alarcón A, Kestler M, Mari-Hualde A, Moreno A, Goenaga MÁ, Fariñas MC, Rodríguez-Álvarez R, Ojeda-Burgos G, Gálvez-Acebal J, Hidalgo-Tenorio C, Noureddine M, Miró JM; GAMES Investigators. Prevalence of Colorectal Neoplasms Among Patients With Enterococcus faecalis Endocarditis in the GAMES Cohort (2008-2017). Mayo Clin Proc. 2021 Jan;96(1):132-146. doi: 10.1016/j.mayocp.2020.06.056.
• Pericàs JM, Llopis J, Muñoz P, Gálvez-Acebal J, Kestler M, Valerio M, Hernández-Meneses M, Goenaga MÁ, Cobo-Belaustegui M, Montejo M, Ojeda-Burgos G, Sousa-Regueiro MD, de Alarcón A, Ramos-Martínez A, Miró JM; GAMES Investigators. A Contemporary Picture of Enterococcal Endocarditis. J Am Coll Cardiol. 2020 Feb 11;75(5):482-494. doi: 10.1016/j.jacc.2019.11.047. Erratum in: J Am Coll Cardiol. 2020 Jun 16;75(23):2998-3000.
• del Río A, Gasch O, Moreno A, Peña C, Cuquet J, Soy D, Mestres CA, Suárez C, Pare JC, Tubau F, Garcia de la Mària C, Marco F, Carratalà J, Gatell JM, Gudiol F, Miró JM; FOSIMI Investigators. Efficacy and safety of fosfomycin plus imipenem as rescue therapy for complicated bacteremia and endocarditis due to methicillin-resistant Staphylococcus aureus: a multicenter clinical trial. Clin Infect Dis. 2014 Oct 15;59(8):1105-12. doi: 10.1093/cid/ciu580. Epub 2014 Jul 21.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 27, 2009): 50
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: April 15, 2015
• Actual Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Suspected methicillin-resistant staphyloccocus aureus infective endocarditis on a native valve, prosthetic valve or pacemakers´s electrode or defibrillators with definitive or probable diagnosis by the modified Duke criteria (Li J, et al. Clin Infect Dis. 2000).
• Patients over 18 years.

Exclusion Criteria:

• Patients who did not sign informed consent.
• Patients with active consumption intravenous drug.
• Patients with emergent surgery criteria (<72 hours).
• Patients or cardiogenic shock.
• Patients with antibiotic active against MRSA over 72 hours or they may need another antibiotic active against MRSA than those in the study.
• Patients with chronic renal failure on hemodialysis who received empirical treatment with vancomycin as a single dose and have a valley ≥ 15 mcg / mL on the third day.
• Patients with MRSA strains resistant to fosfomycin (MIC> 64 mg / L) (<10%) or vancomycin (MIC> 2 mg / L) or with an MIC to vancomycin of 2 mg / L.
• Patients with any formal contraindication to be treated with study drugs
• Patients treated with any investigational drug within 30 days prior to entering the study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Spain

Administrative Information

• NCT Number: NCT00871104
• Other Study ID Numbers: FOSIMI; EudraCT number: 2008-008683-28
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Juan A. Arnaiz, Hospital Clinic of Barcelona
• Study Sponsor: Juan A. Arnaiz
• Collaborators: Not Provided

Investigators

• Principal Investigator: Asunción Moreno Camacho, MD; Hospital Clínic of Barcelona

• PRS Account: Hospital Clinic of Barcelona
• Verification Date: March 2018