Empirical vs 2nd Line Antibiotic Therapy in Health-care Associated Infections in Cirrhosis

NCT ID: NCT01820026

Last Updated: 2015-05-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

96 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-12-31

Study Completion Date

2015-06-30

Brief Summary

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Bacterial infections are a frequent complication in liver cirrhosis with a bad prognosis. However, the clinical outcome of cirrhotic patients with serious infections is significantly improved over the last 30 years due to early diagnosis and to the use of a more appropriate antibiotic therapy.

As in the general population, empirical treatment should be initiated soon after diagnosis, after making the necessary sampling and should be based on the use of an antibiotic with low toxicity and broad spectrum antibacterial efficacy, taking into account the local epidemiology and prevalence of antibiotic resistance.

The third generation cephalosporins are considered the gold standard in the treatment of most infections in cirrhotics due to their effectiveness against enterobacteriaceae and against non-enterococcal streptococci and due to their low toxicity.

However, the recommendations for the antibiotic therapy are currently based on results of trials of '80s and '90s, when the proportion of resistant pathogens was lower. Similarly to nosocomial infections, the increasing rate of infections due to multidrug resistant (MDR) bacteria represents the rational for a different choice of empirical antibiotic therapy with a higher resistance barrier. This change in the epidemiology of community acquired infections is mainly due to the increased contacts with healthcare system of these patients and for the larger use of antibiotic prophylaxis. With this regard, it was recently proposed to introduce a third epidemiological class of infection "Health care-associated": Infections occurring in community in patients who have been in contact with the health system shortly before the infection.

This epidemiological class of infection should be distinguished from "community-acquired" because they are more similar to"nosocomial" in terms of their sensitivity to antibiotics. Therefore for this class should be taken into consideration the use of a different empirical antibiotic therapy.

The investigators aim was to evaluate prospectively the effectiveness of a broad spectrum antibiotic treatment in a cohort of cirrhotic patients with "healthcare-Associated"infections

Cirrhotic patients with "Healthcare Associated" admitted to the gastroenterology department of the Policlinico Umberto I and in the Department of Hepatology of the Hospital of Marino will be consecutively enrolled.

Randomized controlled trial with randomisation stratified by epidemiological class of infection.

Detailed Description

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Unblinded randomized controlled trial with randomisation stratified by epidemiological class of infection.

After obtaining informed consent at enrollment, participants will undergo medical examination with a detailed anamnesis and will begin collecting data on the following parameters:

* Demographic characteristics (age, sex, etiology of cirrhosis, when the diagnosis was made).
* Severity of liver disease(defined by the Child-Pugh classification, MELD score), indices of renal function and serum electrolytes.
* APACHE score in the case of development of sepsis
* Compensated cirrhosis / decompensated cirrhosis
* If decompensated, will be listed complications (ascites, esophageal-gastric varices, hepatic encephalopathy, coagulopathy, Hepato-Renal Syndrome, variceal bleeding).
* Treatment and dosage (eg β-blockers, diuretics)
* Hemodynamic parameters (heart rate / blood pressure)

Patients enrolled will be randomized and treated with conventional therapy provided for community-acquired infections or with the "2nd line antibiotic therapy", based on use of of imipenem-cilastatin.

The protocol of antibiotic therapy chosen for this category of patients will be based on a antibiotic class recommended for a specific site of infection in international guidelines for the treatment of nosocomial infections and / or healthcare associated with a high safety profile and is already used in the investigators hospital. The cost of empirical treatment with imipenem / cilastatin is roughly comparable to that with the currently used first-line antibiotics for such infections, and frequently used drugs in the forefront of these patients are ineffective is therefore necessary to embark on a new antibiotic with higher costs also in terms of days of hospitalization.

During the hospitalization will be recorded the type of infection, empirical therapy, its duration, side effects, isolated pathogens and their resistance, when available, the occurrence of complications related to infection and mortality.

The efficacy of therapy will be assessed based on the resolution of infection attested by normalization of clinical , biochemical and microbiological parameters and the instrumental tools.

Conditions

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Cirrhosis

Keywords

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healthcare infection cirrhosis antibiotic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Imipenem & Vancomycin & Azithromycin

Tienam combined with vancomycin (1g/12 h) for Spontaneous bacterial peritonitis, cholangitis, sepsis without evidence of a source of infections.

Tienam combined with vancomycin (1g/12 h)and azythromycin (500 mg/24 h)for pneumonia

Group Type EXPERIMENTAL

Imipenem

Intervention Type DRUG

second line therapy

Vancomycin

Intervention Type DRUG

Second line therapy

azithromycin

Intervention Type DRUG

Second line therapy

Cefotaxime & Amoxicillin & Azithromycin

Cefotaxime IV(2g/12 h): for Spontaneous bacterial peritonitis, cholangitis, sepsis without evidence of specific site of infection Amoxicillin/clavulanic acid (2,2 g/8 h)or Ciprofloxacin (500 mg/12 h: urinary tract infections Amoxicillin/clavulanic acid (2,2 g/8 h)and azithromycin (500 mg/24 h): pneumonia Amoxicillin/clavulanic acid (2,2 g/8 h)for skin or soft tissue infection

Group Type ACTIVE_COMPARATOR

azithromycin

Intervention Type DRUG

Second line therapy

Cefotaxime

Intervention Type DRUG

Standard antibiotic therapy

Amoxicillin

Intervention Type DRUG

Standard therapy

Interventions

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Imipenem

second line therapy

Intervention Type DRUG

Vancomycin

Second line therapy

Intervention Type DRUG

azithromycin

Second line therapy

Intervention Type DRUG

Cefotaxime

Standard antibiotic therapy

Intervention Type DRUG

Amoxicillin

Standard therapy

Intervention Type DRUG

Other Intervention Names

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Tienam Vancocyn Zithromax Augmentin

Eligibility Criteria

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Inclusion Criteria

* cirrhosis
* healthcare infection
* older than 18 years
* agreement to participate

Exclusion Criteria

* HIV
* patients underwent to liver transplantation
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Roma La Sapienza

OTHER

Sponsor Role lead

Responsible Party

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Manuela Merli

Prof

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Manuela Merli, Prof

Role: PRINCIPAL_INVESTIGATOR

Gastroenterology

Claudio Puoti, Prof

Role: STUDY_CHAIR

Department of Medicine Epatologica Marino Hospital

Locations

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Manuela Merli

Rome, Rome, Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Manuela Merli, Prof

Role: CONTACT

Phone: 00390649972001

Email: [email protected]

Cristina Lucidi, Dr

Role: CONTACT

Phone: 00393395263376

Email: [email protected]

Facility Contacts

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Manuela Merli, Prof

Role: primary

Cristina Lucidi, Dr

Role: backup

References

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Merli M, Lucidi C, Di Gregorio V, Lattanzi B, Giannelli V, Giusto M, Farcomeni A, Ceccarelli G, Falcone M, Riggio O, Venditti M. An empirical broad spectrum antibiotic therapy in health-care-associated infections improves survival in patients with cirrhosis: A randomized trial. Hepatology. 2016 May;63(5):1632-9. doi: 10.1002/hep.28332. Epub 2016 Jan 5.

Reference Type DERIVED
PMID: 26529126 (View on PubMed)

Other Identifiers

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Infection and Cirrhosis

Identifier Type: -

Identifier Source: org_study_id