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

NCT01455246 | Terminated Phase 2

• 2 other identifiers: 2059P2010-019625-34
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (3)

• Mortality during hospitalization

  participants will be followed for the duration of hospital stay, an expected average of 6 weeks

• 30 days mortality

  30 days

• 90 days mortality

  90 days

Study Arms (2)

Daptomycin + Meropenem

EXPERIMENTAL

30 patients with cirrhosis and nosocomial SBP

Drug: Daptomycin + Meropenem

Ceftazidime

ACTIVE COMPARATOR

30 patients with cirrhosis and nosocomial SBP

Drug: Ceftazidime

Interventions

Daptomycin + Meropenem DRUG

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.

Daptomycin + Meropenem

Ceftazidime DRUG

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

Ceftazidime

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Padova: lead

Study Sites (1)

Dept. of Clinical and Experimental Medicine, University of Padova

Padua, PD, 35128, Italy

Location

Related Publications (4)

• 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.

  PMID: 10673079 BACKGROUND

• 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.

  PMID: 17187409 BACKGROUND

• 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.

  PMID: 16393283 BACKGROUND

• 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.

  PMID: 19302016 BACKGROUND

MeSH Terms

Conditions

Fibrosis; Ascites; Cross Infection; Sepsis

Interventions

Daptomycin; Meropenem; Ceftazidime

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infections; Iatrogenic Disease; Disease Attributes; Systemic Inflammatory Response Syndrome; Inflammation

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Peptides; Amino Acids, Peptides, and Proteins; Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cephaloridine; Cephalosporins; Thiazines; Sulfur Compounds

Study Officials

• Paolo Angeli, MD, PhD

  Dept. of Clinical and Experimenatl Medicine, University of Padova, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 13, 2011
• First Posted: October 19, 2011
• Study Start: October 1, 2010
• Primary Completion: April 1, 2014
• Study Completion: July 1, 2014
• Last Updated: October 15, 2014

Record last verified: 2014-10

Locations

IT (1)