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Daptomycin + Meropenem Versus Ceftazidime in the Treatment of Nosocomial Spontaneous Bacterial Peritonitis

This study has been terminated.
(Decision of independent monitoring committee after interim analysis: Risk of failure significantly higher in ceftazidime group.)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01455246
First Posted: October 19, 2011
Last Update Posted: October 15, 2014
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by:
University of Padova
  Purpose
Nosocomial spontaneous bacterial peritonitis (SBP) is frequently caused by multi drug resistant bacteria. Standard treatment of SBP could be ineffective. The aim of the study is to compare daptomycin + meropenem vs ceftazidime in the treatment of nosocomial SBP.

Condition Intervention Phase
Cirrhosis Ascites Nosocomial Spontaneous Bacterial Peritonitis Drug: Daptomycin + Meropenem Drug: Ceftazidime Phase 2 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Daptomycin + Meropenem Versus Ceftazidime in the Treatment of Nosocomial Spontaneous Bacterial Peritonitis: an Open, Randomized, Controlled Clinical Trial

Resource links provided by NLM:


Further study details as provided by University of Padova:

Primary Outcome Measures:
  • The primary end-point of the study is the response to therapy [ Time Frame: 48 hours and seven days ]
    The response to therapy is defined as the reduction of polymorphonuclear leukocytes (PMN) count in ascitic fluid more than 25 % from baseline after 48 hours and as a PMN count in ascitic fluid less then 250/mm³ after seven days.


Secondary Outcome Measures:
  • Mortality during hospitalization [ Time Frame: participants will be followed for the duration of hospital stay, an expected average of 6 weeks ]
  • 30 days mortality [ Time Frame: 30 days ]
  • 90 days mortality [ Time Frame: 90 days ]

Enrollment: 32
Study Start Date: October 2010
Study Completion Date: July 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Daptomycin + Meropenem
30 patients with cirrhosis and nosocomial SBP
Drug: Daptomycin + Meropenem
Daptomycin will be administered at the dose of 6 mg/kg every 24 hours and 6 mg/kg every 48 hours for an estimated creatinine clearance (CKD-EPI) of > 30 ml/min and < 30 ml/min respectively. Meropenem will be administered at the dose of 1 g t.i.d., 1 g b.i.d., 0.5 g every 24 hours for an estimated creatinine clearance of >50 ml/min, 10-50 ml/min, and < 10 ml/min respectively. The treatment will go on for 7 days. In the patients without response to treatment after 48 hours will be added a rescue therapy with fluconazole. In patients in which cultures shown a bacterial species resistant to therapy, daptomycin and meropenem will be discontinued and replaced by a therapy based on antibiotic susceptibility of isolated species.
Active Comparator: Ceftazidime
30 patients with cirrhosis and nosocomial SBP
Drug: Ceftazidime
Ceftazidime will be administered at the dose of 2 g t.i.d, 2 g b.i.d and 2 g at every 24 hours by intravenous infusion for an estimated creatinine clearance (CKD-EPI) of >50 ml/min, 10-50 ml/min, and < 10 ml/min respectively. The treatment will go on for 7 days. In the patients without response to treatment after 48 hours, or in which cultures shown a bacterial species resistant to therapy, ceftazidime will be discontinued and replaced by a rescue therapy with meropenem and daptomycin as provided for the experimental arm

Detailed Description:
Spontaneous bacterial peritonitis (SBP) is a well known complication in patients with liver cirrhosis and ascites. Nosocomial SBP is defined as SBP that occurs after 48 hours of hospitalization. It has been shown that patients with nosocomial SBP have a worse prognosis than patients with community-acquired SBP. It has also been shown that nosocomial SBP is frequently caused by multi drug resistant bacteria such as extended-spectrum-beta-lactamase (ESBL) producing enterobacteria or meticillin - resistant staphylococcus aureus. Currently the empirical treatment of SBP is the use of third generation cephalosporins or amoxicillin/clavulanic acid. In patients affected by nosocomial SBP these treatment could be ineffective. Up to now an empirical approach with a broader spectrum strategy (such as an association between meropenem and daptomycin) has never been compared to standard therapy in the treatment of nosocomial SBP. Thus, the aim of the study is to compare daptomycin + meropenem vs ceftazidime in the treatment of nosocomial SBP in patients with cirrhosis.
  Eligibility

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with liver cirrhosis and ascites
  • Meets all criteria for nosocomial SBP as outlined below

    • Ascitic fluid polymorphonuclear cells count >250/mm3
    • Onset of signs and symptoms of infection after 72 hours of hospitalization

Exclusion Criteria:

  • Hepatocellular carcinoma beyond the Milan criteria
  • Abdominal surgery within 4 weeks
  • Evidence of secondary peritonitis, pancreatitis or peritoneal carcinomatosis
  • Significant heart or respiratory failure
  • Allergy to ceftazidime, meropenem or daptomycin
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01455246


Locations
Italy
Dept. of Clinical and Experimental Medicine, University of Padova
Padova, PD, Italy, 35128
Sponsors and Collaborators
University of Padova
Investigators
Principal Investigator: Paolo Angeli, MD, PhD Dept. of Clinical and Experimenatl Medicine, University of Padova, Italy
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT01455246     History of Changes
Other Study ID Numbers: 2059P
2010-019625-34 ( EudraCT Number )
First Submitted: October 13, 2011
First Posted: October 19, 2011
Last Update Posted: October 15, 2014
Last Verified: October 2014

Keywords provided by University of Padova:
Cirrhosis
Nosocomial Spontaneous Bacterial Peritonitis
Ascites
Daptomycin
Meropenem
Ceftazidime
Nosocomial infection
Multi drug resistant bacteria
Sepsis
Albumin

Additional relevant MeSH terms:
Fibrosis
Ascites
Peritonitis
Pathologic Processes
Intraabdominal Infections
Infection
Peritoneal Diseases
Digestive System Diseases
Meropenem
Thienamycins
Daptomycin
Ceftazidime
Anti-Bacterial Agents
Anti-Infective Agents