Clinical trial NCT01455246: Daptomycin + Meropenem Versus Ceftazidime in the Treatment of Nosocomial Spontaneous Bacterial Peritonitis
Official title: Daptomycin + Meropenem Versus Ceftazidime in the Treatment of Nosocomial Spontaneous Bacterial Peritonitis: an Open, Randomized, Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Cirrhosis
Ascites
Nosocomial Spontaneous Bacterial Peritonitis
Keywords: Cirrhosis
Nosocomial Spontaneous Bacterial Peritonitis
Ascites
Daptomycin
Meropenem
Ceftazidime
Nosocomial infection
Multi drug resistant bacteria
Sepsis
Albumin
Lead sponsor: University of Padova
Sponsor class: OTHER
First posted: 2011-10-19
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: The primary end-point of the study is the response to therapy
timeFrame: 48 hours and seven days
Secondary outcomes:
measure: Mortality during hospitalization
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 6 weeks
measure: 30 days mortality
timeFrame: 30 days
measure: 90 days mortality
timeFrame: 90 days
Other outcomes:
Locations:
city: Padova
country: Italy
facility: Dept. of Clinical and Experimental Medicine, University of Padova
state: PD
Study officials:
affiliation: Dept. of Clinical and Experimenatl Medicine, University of Padova, Italy
name: Paolo Angeli, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rimola A, Garcia-Tsao G, Navasa M, Piddock LJ, Planas R, Bernard B, Inadomi JM. Diagnosis, treatment and prophylaxis of spontaneous bacterial peritonitis: a consensus document. International Ascites Club. J Hepatol. 2000 Jan;32(1):142-53. doi: 10.1016/s0168-8278(00)80201-9. No abstract available.
citation: Fasolato S, Angeli P, Dallagnese L, Maresio G, Zola E, Mazza E, Salinas F, Dona S, Fagiuoli S, Sticca A, Zanus G, Cillo U, Frasson I, Destro C, Gatta A. Renal failure and bacterial infections in patients with cirrhosis: epidemiology and clinical features. Hepatology. 2007 Jan;45(1):223-9. doi: 10.1002/hep.21443.
citation: Angeli P, Guarda S, Fasolato S, Miola E, Craighero R, Piccolo F, Antona C, Brollo L, Franchin M, Cillo U, Merkel C, Gatta A. Switch therapy with ciprofloxacin vs. intravenous ceftazidime in the treatment of spontaneous bacterial peritonitis in patients with cirrhosis: similar efficacy at lower cost. Aliment Pharmacol Ther. 2006 Jan 1;23(1):75-84. doi: 10.1111/j.1365-2036.2006.02706.x.
citation: Cheong HS, Kang CI, Lee JA, Moon SY, Joung MK, Chung DR, Koh KC, Lee NY, Song JH, Peck KR. Clinical significance and outcome of nosocomial acquisition of spontaneous bacterial peritonitis in patients with liver cirrhosis. Clin Infect Dis. 2009 May 1;48(9):1230-6. doi: 10.1086/597585.