Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001247167
Ethics application status
Approved
Date submitted
31/07/2019
Date registered
10/09/2019
Date last updated
10/09/2019
Date data sharing statement initially provided
10/09/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Prospective Clinical Drug-Drug Interaction study between Rifampicin and Fusidic Acid
Scientific title
Prospective Clinical Drug-Drug Interaction study between Rifampicin and Fusidic Acid in the context of staphylococcal infection
Secondary ID [1] 298815 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Medication interaction 313765 0
Condition category
Condition code
Infection 312173 312173 0 0
Other infectious diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Observation pharmacokinetic study measuring blood levels of Rifampicin and Fusidic acid in patients prescribed this combination for Methicillin-susceptible Staphylococcal infections for a period of 28 +/- 7 days per patient.
Intervention code [1] 315100 0
Not applicable
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 320825 0
Composite primary outcome will be the 90% confidence interval around the geometric mean ratio of estimated plasma area under the curve (AUC) of both rifampicin and fusidic acid at steady state when given in combination compared with when given alone.
Timepoint [1] 320825 0
Day 0, Day 1 and Day 28 (+/-7)
Secondary outcome [1] 372966 0
The result of the treatment of the infection as determined by review of medical records from treating clinicians
Timepoint [1] 372966 0
28 (+/-7) days
Secondary outcome [2] 374291 0
Adverse effects resulting from the study medications. For example, drug-induced liver injury as assessed by biomarkers of liver function and medical records or participant self-reported nausea and vomiting
Timepoint [2] 374291 0
28 +/- 7 days

Eligibility
Key inclusion criteria
-Inpatients with presumed or confirmed staphylococcal infection
-A decision to treat with oral rifampicin and fusidic acid has already been made but not started.
-Treatment with an intravenous beta-lactam antibiotic
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
-Previous adverse reaction to rifampicin or fusidic acid
-Pregnancy
-The taking of other essential medications with a known significant interaction with rifampicin and fusidic acid
-Liver failure
-Unlikely to receive antibiotic treatment for longer than 4 weeks
-Primary intravenous treatment with vancomycin or teicoplanin
-Already on treatment with intravenous rifampicin

Study design
Purpose
Duration
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Sample size calculation: Power calculations have been performed within NONMEM using Monte-Carlo mapped power implemented via Perl-Speaks-NONMEM. Base models were taken from previously published population pharmacokinetic models. Based on previous data, for fusidic acid, an increased clearance alone was assumed, while for rifampicin a decreased clearance and volume was assumed. The power to detect these differences between two doses with an alpha of 0.05 (significance level of 5%) was determined and then plotted for each 10% of change. The least sensitive model to detect a change was that of fusidic acid, therefore, the sample size was based on these results. To detect a 30% change (potentially clinically relevant) with a power of 90% then 8 subjects would be required. Considering potential dropouts and incomplete datasets a target number of 12 has been set.

Statistical Analysis: Estimated plasma-time concentration data will be analyzed by non-linear mixed-effects modeling. Once a model is established, pharmacokinetic parameters including AUC and elimination half-life will be predicted. Relationships between predicted model parameters and age, weight, albumin level, bilirubin, hematocrit value, and creatinine clearance rate will be evaluated with a stepwise forward-inclusion and backward-elimination regression analysis. Randomization will be achieved using Microsoft Excel (version 15.35).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
27/08/2019
Date of last participant enrolment
Anticipated
30/12/2019
Actual
Date of last data collection
Anticipated
28/01/2020
Actual
Sample size
Target
12
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 14332 0
St Vincent's Private Hospital - Fitzroy
Recruitment hospital [2] 14333 0
The Northern Hospital - Epping
Recruitment postcode(s) [1] 27335 0
3065 - Fitzroy
Recruitment postcode(s) [2] 27336 0
3076 - Epping

Funding & Sponsors
Funding source category [1] 303368 0
Hospital
Name [1] 303368 0
St Vincent's Hospital Melbourne - Infectious Diseases Research Fund
Country [1] 303368 0
Australia
Primary sponsor type
Hospital
Name
St Vincent's Hospital Melbourne
Address
41-55 Victoria Pde Fitzroy Victoria 3065
Country
Australia
Secondary sponsor category [1] 303457 0
None
Name [1] 303457 0
Address [1] 303457 0
Country [1] 303457 0
Other collaborator category [1] 280879 0
University
Name [1] 280879 0
Curtin University
Address [1] 280879 0
Kent St, Bentley WA 6102
Country [1] 280879 0
Australia
Other collaborator category [2] 280880 0
University
Name [2] 280880 0
University of Western Australia
Address [2] 280880 0
35 Stirling Hwy, Crawley WA 6009
Country [2] 280880 0
Australia
Other collaborator category [3] 280881 0
Hospital
Name [3] 280881 0
The Northern Hospital
Address [3] 280881 0
185 Cooper St, Epping VIC 3076
Country [3] 280881 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303898 0
Human Research Ethics Committee - St Vincent's Hospital Melbourne
Ethics committee address [1] 303898 0
Ethics committee country [1] 303898 0
Australia
Date submitted for ethics approval [1] 303898 0
Approval date [1] 303898 0
13/06/2019
Ethics approval number [1] 303898 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 95174 0
A/Prof Craig Aboltins
Address 95174 0
St Vincent's Hospital, Melbourne - 41 Victoria Pde, Fitzroy VIC 3065
Country 95174 0
Australia
Phone 95174 0
+613 9231 2211
Fax 95174 0
+613 9231 4068
Email 95174 0
[email protected]
Contact person for public queries
Name 95175 0
Callum Maggs
Address 95175 0
St Vincent's Hospital, Melbourne - 41 Victoria Pde, Fitzroy VIC 3065
Country 95175 0
Australia
Phone 95175 0
+613 9231 2211
Fax 95175 0
+613 9231 4068
Email 95175 0
[email protected]
Contact person for scientific queries
Name 95176 0
Craig Aboltins
Address 95176 0
St Vincent's Hospital, Melbourne - 41 Victoria Pde, Fitzroy VIC 3065
Country 95176 0
Australia
Phone 95176 0
+613 9231 2211
Fax 95176 0
+613 9231 4068
Email 95176 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual data sharing is not included in the consent process for this study


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.