Daptomycin + Meropenem Versus Ceftazidime in the Treatment of Nosocomial Spontaneous Bacterial Peritonitis - Full Text View

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 Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: 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:

Genetics Home Reference related topics: North American Indian childhood cirrhosis

MedlinePlus related topics: Cirrhosis

Drug Information available for: Ceftazidime sodium Ceftazidime Meropenem Daptomycin

U.S. FDA Resources

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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
30 days mortality [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
90 days mortality [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	60
Study Start Date:	October 2010
Estimated Study Completion Date:	January 2014
Estimated Primary Completion Date:	October 2013 (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

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

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01455246

Contacts

Contact: Paolo Angeli, MD, PhD	+39-049-8212004	pangeli@unipd.it
Contact: Salvatore Piano, MD	+39-049-8211836	salvatoresilvio.piano@unipd.it

Locations

Italy
Dept. of Clinical and Experimental Medicine, University of Padova	Recruiting
Padova, PD, Italy, 35128
Contact: Paolo Angeli, MD, PhD +39-049-8212004 pangeli@unipd.it
Contact: Salvatore Piano, MD +39-049-8211836 salvatoresilvio.piano@unipd.it
Principal Investigator: Paolo Angeli, MD, PhD
Sub-Investigator: Salvatore Piano, MD

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:

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. No abstract available.

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.

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.

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.

ClinicalTrials.gov Identifier:	NCT01455246 History of Changes
Other Study ID Numbers:	2059P, 2010-019625-34
Study First Received:	October 13, 2011
Last Updated:	October 17, 2011
Health Authority:	Italy: Ministry of Health

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:

Ascites
Liver Cirrhosis
Fibrosis
Peritonitis
Pathologic Processes
Liver Diseases
Digestive System Diseases
Peritoneal Diseases

Ceftazidime
Daptomycin
Meropenem
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 18, 2013