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

Cirrhosis Clinical Trial

Official title:

Daptomycin + Meropenem Versus Ceftazidime in the Treatment of Nosocomial Spontaneous Bacterial Peritonitis: an Open, Randomized, Controlled Clinical Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01455246
• Other study ID #: 2059P
• Secondary ID: 2010-019625-34
• Status: Terminated
• Phase: Phase 2/Phase 3
• First received: October 13, 2011
• Last updated: October 11, 2014
• Start date: October 2010
• Est. completion date: July 2014

Study information

• Verified date: October 2014
• Source: University of Padova
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 32
• Est. completion date: July 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ascites
• Cirrhosis
• Nosocomial Spontaneous Bacterial Peritonitis
• Peritonitis

Intervention

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.
• 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

Locations

Country	Name	City	State
Italy	Dept. of Clinical and Experimental Medicine, University of Padova	Padova	PD

Sponsors (1)

Lead Sponsor	Collaborator
University of Padova

Country where clinical trial is conducted

Italy, 

References & Publications (4)

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. — View 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. — View Citation

Fasolato S, Angeli P, Dallagnese L, Maresio G, Zola E, Mazza E, Salinas F, Donà 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. — View Citation

Rimola A, García-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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary end-point of the study is the response to therapy	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.	48 hours and seven days	Yes
Secondary	Mortality during hospitalization		participants will be followed for the duration of hospital stay, an expected average of 6 weeks	Yes
Secondary	30 days mortality		30 days	Yes
Secondary	90 days mortality		90 days	Yes