Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12609001076268
Ethics application status
Approved
Date submitted
28/11/2009
Date registered
16/12/2009
Date last updated
10/07/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
A randomised controlled study of high dose versus standard dose antibiotics for the prevention of bacterial sepsis in advanced liver disease
Scientific title
A randomised controlled study of high dose versus standard dose antibiotics for the prevention of bacterial sepsis in advanced liver disease
Secondary ID [1] 1199 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
cirrhosis 4887 0
bacterial infection 252306 0
Condition category
Condition code
Oral and Gastrointestinal 237240 237240 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Infection 252486 252486 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment with high dose (twice daily) trimethoprim-sulfamethoxazole 160mg-800mg oral tablet for 12 months to prevent bacterial infections in patients with cirrhosis
Intervention code [1] 236675 0
Treatment: Drugs
Intervention code [2] 255695 0
Prevention
Comparator / control treatment
Treatment with standard dose (once daily) trimethoprim-sulfamethoxazole 160mg-800mg oral tablet for 12 months to prevent bacterial infections in patients with cirrhosis
Control group
Dose comparison

Outcomes
Primary outcome [1] 238055 0
Incidence of bacterial infection with diagnosis based on positive microbiological culture, documented radiological changes consistent with infection or established clinical diagnosis
Timepoint [1] 238055 0
Every 3 months following randomisation for 12 months
Primary outcome [2] 253380 0
Incidence of admission to hospital for other complications of chronic liver disease based on prospective follow up and review of medical records
Timepoint [2] 253380 0
Every 3 months following randomisation for 12 months
Secondary outcome [1] 242242 0
Rate of extraperitoneal infection requiring antibiotic therapy based on positive microbiological culture, documented radiological changes consistent with infection or established clinical diagnosis
Timepoint [1] 242242 0
Every 3 months following randomisation for 12 months
Secondary outcome [2] 262461 0
Rate of peritoneal bacterial infection requiring antibiotic therapy based on positive microbiological culture or elevated white blood cell/neutrophil count consistent with established diagnostic criteria
Timepoint [2] 262461 0
Every 3 months following randomisation for 12 months
Secondary outcome [3] 262462 0
Rate of bacteraemia based on positive microbiological culture or established clinical diagnosis
Timepoint [3] 262462 0
Every 3 months following randomisation for 12 months
Secondary outcome [4] 262463 0
Rate of hepatorenal syndrome based on blood and urine analysis meeting established diagnostic criteria
Timepoint [4] 262463 0
Every 3 months following randomisation for 12 months
Secondary outcome [5] 262464 0
Mortality rate based on prospective follow up and review of medical records
Timepoint [5] 262464 0
Every 3 months following randomisation for 12 months
Secondary outcome [6] 262465 0
Side effects and tolerability of trimethoprim-sulfamethoxazole daily and twice daily. Possible side effects include nausea, loss of appetite, rash, abnormal cell counts and elevated potassium levels. This will be assessed by interview of patient and review of blood tests.
Timepoint [6] 262465 0
Every 3 months following randomisation for 12 months
Secondary outcome [7] 262466 0
Resistance rates to trimethoprim-sulfamethoxazole in organisms isolated during the study based on documented event of infection and proven resistance on microbiological culture and sensitivity testing.
Timepoint [7] 262466 0
Every 3 months following randomisation for 12 months

Eligibility
Key inclusion criteria
Patient with cirrhosis and ascites
Between 18 and 80 years of age
Able to give informed consent
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Allergies to trimethoprim-sulfamethoxazole or sulfa
Previous documented failure of trimethoprim-sulfamethoxazole
Severe renal impairment
Hepatocellular carcinoma, malignancy or other conditions associated with expected survival of less than 3 months
Current bacterial infection

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients meeting inclusion criteria will be invited to enrol
Informed consent will be obtained prior to randomisation
Randomisation will be computer generated and sealed in opaque envelope
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Opaque envelope with preallocated treatment arm computer generated and randomly selected
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
23/11/2009
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
90
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 256102 0
Hospital
Name [1] 256102 0
Austin Health
Country [1] 256102 0
Australia
Primary sponsor type
Hospital
Name
Austin Health
Address
Studley Road
Heidelberg Vic 3084
Country
Australia
Secondary sponsor category [1] 251448 0
None
Name [1] 251448 0
Address [1] 251448 0
Country [1] 251448 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 258188 0
Human Research Ethics Committee
Ethics committee address [1] 258188 0
Research Ethics Unit
Henry Buck Building
Austin Health
Studley Road
Heidelberg Vic 3084
Ethics committee country [1] 258188 0
Australia
Date submitted for ethics approval [1] 258188 0
Approval date [1] 258188 0
19/08/2009
Ethics approval number [1] 258188 0
H2009/03622

Summary
Brief summary
Patients with advanced liver disease and ascites (intra-abdominal fluid) are at high risk of bacterial infections such as spontaneous bacterial peritonitis. Once daily antibiotics such as trimethoprim-sulfamethoxazole is considered standard treatment to prevent bacterial infections in this setting. However, breakthrough infections are still common. The study hypothesis is that a higher dose of antibiotics may be more effective in preventing bacterial infections in advanced liver disease. The purpose is therefore to conduct a trial to examine whether twice daily trimethoprim-sulfamethoxazole is more effective than the standard once daily dose at reducing bacterial infections and admissions to hospital in these high risk patients.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29673 0
Address 29673 0
Country 29673 0
Phone 29673 0
Fax 29673 0
Email 29673 0
Contact person for public queries
Name 12920 0
Dr Rohit Sawhney
Address 12920 0
Department of Gastroenterology
Austin Health
Level 8, Harold Stokes Building
Studley Road
Heidelberg Vic 3084
Country 12920 0
Australia
Phone 12920 0
+61 3 94965353
Fax 12920 0
Email 12920 0
[email protected]
Contact person for scientific queries
Name 3848 0
Dr Paul Gow
Address 3848 0
Department of Gastroenterology
Austin Health
Level 8, Harold Stokes Building
Studley Road
Heidelberg Vic 3084
Country 3848 0
Australia
Phone 3848 0
+61 3 94965859
Fax 3848 0
Email 3848 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.