CirrhosisPhase 4NCT01820026
Empirical vs 2nd Line Antibiotic Therapy in Health-care Associated Infections in Cirrhosis
A Phase 4 study testing Imipenem, Vancomycin and azithromycin in people with Cirrhosis, run by University of Roma La Sapienza at 1 site in Italy.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cirrhosis
- What is being tested?
- Imipenem, Vancomycin and azithromycin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 96 participants
- Where
- 1 siteItaly
- Study dates
- Dec 2012to Jun 2015
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- cirrhosis
- healthcare infection
- older than 18 years
- agreement to participate
Who cannot join
- HIV
- patients underwent to liver transplantation
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Manuela Merli
Rome, Rome, 00100
Manuela Merli, Prof, 00300649972001, clucidi@hotmail.it
Cristina Lucidi, Dr, 00393395263376, clucidi@hotmail.it
About this study
Official title: Bacterial Infections Associated With Healthcare (Healthcare-Associated) in Hospitalized Cirrhotic Patients: Randomized Study of Use of Traditional Empirical Antibiotic Therapy and Second-line Targeted at Multi-resistant Bacteria
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.
Read more
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.
Read the detailed description
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
- Cirrhosis
- Being tested
- Imipenem, Vancomycin, azithromycin, Cefotaxime, Amoxicillin
- Keywords
- healthcare infection cirrhosis antibiotic
- Medical subject headings
- Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ImipenemDrug
Also called Tienam
second line therapy
VancomycinDrug
Also called Vancocyn
Second line therapy
azithromycinDrug
Also called Zithromax
Second line therapy
CefotaximeDrug
Standard antibiotic therapy
AmoxicillinDrug
Also called Augmentin
Standard therapy
| Study group | Role | What they receive |
|---|---|---|
| Imipenem & Vancomycin & Azithromycin | Experimental | 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 Receives: Drug: Imipenem; Drug: Vancomycin; Drug: azithromycin |
| Cefotaxime & Amoxicillin & Azithromycin | Active comparator | 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 Receives: Drug: azithromycin; Drug: Cefotaxime; Drug: Amoxicillin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of anti-multiresistant empirical antibiotic therapy in healthcare associated infections in cirrhosis
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2013 (estimated)
- Study startDec 2012
- Primary completionMay 2015
- Study completionJun 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CirrhosisStudies of the same condition, open and under way.
- More trials run by University of Roma La SapienzaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 96 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Roma La Sapienza
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Manuela Merli, University of Roma La Sapienza
- Investigators
- Manuela Merli, Prof, Principal investigator, GastroenterologyClaudio Puoti, Prof, Study chair, Department of Medicine Epatologica Marino Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01820026
- Sponsor's protocol ID
- Infection and Cirrhosis
- Status last verified
- May 2015
- First submitted
- 16 Oct 2012
- Last updated
- 29 May 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 26529126
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bacterial Infections Associated With Healthcare (Healthcare-Associated) in Hospitalized Cirrhotic Patients: Randomized Study of Use of Traditional Empirical Antibiotic Therapy and Second-line Targeted at Multi-resistant Bacteria
- ClinicalTrials.gov ID
- NCT01820026
- Acronym / sponsor ID
- Infection and Cirrhosis
- Conditions
- Cirrhosis
- Keywords
- healthcare infection cirrhosis antibiotic
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 96 participants (estimated)
- Lead sponsor
- University of Roma La SapienzaUniversity, hospital or other
- Study start
- Dec 2012
- Primary completion
- May 2015 (actual)
- Study completion
- Jun 2015 (estimated)
- First posted
- 28 Mar 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Imipenem & Vancomycin & Azithromycin | Experimental | Drug: Imipenem, Drug: Vancomycin, Drug: azithromycinTienam 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 |
| Cefotaxime & Amoxicillin & Azithromycin | Active comparator | Drug: azithromycin, Drug: Cefotaxime, Drug: AmoxicillinCefotaxime 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- cirrhosis
- healthcare infection
- older than 18 years
- agreement to participate
Key exclusion criteria (2 listed)
- HIV
- patients underwent to liver transplantation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ImipenemAlso: Tienamsecond line therapy | Drug | Imipenem & Vancomycin & Azithromycin |
| VancomycinAlso: VancocynSecond line therapy | Drug | Imipenem & Vancomycin & Azithromycin |
| azithromycinAlso: ZithromaxSecond line therapy | Drug | Cefotaxime & Amoxicillin & Azithromycin, Imipenem & Vancomycin & Azithromycin |
| CefotaximeStandard antibiotic therapy | Drug | Cefotaxime & Amoxicillin & Azithromycin |
| AmoxicillinAlso: AugmentinStandard therapy | Drug | Cefotaxime & Amoxicillin & Azithromycin |
Primary outcome
Efficacy of anti-multiresistant empirical antibiotic therapy in healthcare associated infections in cirrhosis
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2015.
- Derived from this study: PubMed 26529126Merli 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Manuela Merli, Prof principal investigator
Gastroenterology
Claudio Puoti, Prof study chair
Department of Medicine Epatologica Marino Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Imipenem, Vancomycin and azithromycin in people with Cirrhosis, run by University of Roma La Sapienza at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Manuela Merli, Prof (00390649972001, clucidi@hotmail.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy of anti-multiresistant empirical antibiotic therapy in healthcare associated infections in cirrhosis (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01820026, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2015.