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Trial registered on ANZCTR


Registration number
ACTRN12617000278336
Ethics application status
Approved
Date submitted
25/08/2015
Date registered
23/02/2017
Date last updated
23/02/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Induction of Macrolide Resistance Post Azithromycin or Erythromcyin Treatment
Scientific title
intensity of induction of Macrolide Resistance Post Azithromycin or Erythromcyin Treatment in healthy participants
Secondary ID [1] 287223 0
None
Universal Trial Number (UTN)
Trial acronym
The IMPACT trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
macrolide resistance 295826 0
Condition category
Condition code
Respiratory 296084 296084 0 0
Other respiratory disorders / diseases
Infection 296682 296682 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
60 participants will be recruited and randomly assigned to receive either azithromycin (125mg) twice per day or Erythromycin ethylsuccinate 400mg twice per day for 4 weeks orally. adherence to therapy will be monitored by counting the number of tablets retuned after one week and 4 weeks. 80% adherence to therapy will be considered compliant.
Intervention code [1] 292512 0
Treatment: Drugs
Comparator / control treatment
Erythromcyin vs azithromycin
Control group
Active

Outcomes
Primary outcome [1] 295758 0
To determine whether erythromycin and azithromycin differ in their respective propensities to induce macrolide resistance within commensal oropharyngeal flora in healthy participants (index case). Throat swabs will be assessed by PCR and sequencing of the resident streptococcal species. Genetic determinants of macrolide resistance will be assessed before starting the drug, at weeks one and 4 after starting the drug and 30 days after finishing the drug. comparisons to baseline and between each group will be assessed to determine whether there is an increase in macrolide resistance,
Timepoint [1] 295758 0
week 1, week 4 after starting study treatment and 30 days post end of intervention
Secondary outcome [1] 316432 0
To determine whether macrolide resistance also develops in the commensal oropharyngeal flora of close household contacts of the index case, who is consuming macrolides in the short-term (within 4 weeks). Throat swabs will be assessed by PCR and sequencing of the resident streptococcal species. Genetic determinants of macrolide resistance will be assessed before starting the drug, at weeks one and 4, and 30 days after finishing the study. comparisons between treated subjects and their household contacts will be assessed to determine whether there is an increase in macrolide resistance in the untreated group also,
Timepoint [1] 316432 0
week 1, week 4 after starting study treatment and 30 days post end of intervention
Secondary outcome [2] 316433 0
To determine the effect of macrolide antibiotics upon oropharyngeal microbiota composition. Throat swabs will be assessed by PCR and sequencing of the resident streptococcal species. Genetic determinants of macrolide resistance will be assessed before starting the drug, at weeks one and 4 after starting the drug and 30 days after finishing the drug. comparisons to baseline and between each group will be assessed to determine whether there is a difference in macrolide resistance induction between the two drugs,
Timepoint [2] 316433 0
week 1, week 4 after starting study treatment and 30 days post end of intervention
Secondary outcome [3] 316434 0
To determine changes in resistance gene profiles in oropharyngeal flora in response to macrolide antibiotic therapy. Throat swabs will be assessed by PCR and sequencing of the resident streptococcal species. Genetic determinants of macrolide resistance will be assessed before starting the drug, at weeks one and 4 after starting the drug and 30 days after finishing the drug. comparisons to baseline and between each treatment group,
Timepoint [3] 316434 0
week 1, week 4 after starting study treatment and 30 days post end of intervention

Eligibility
Key inclusion criteria
Consenting individual
Non-smoker
Nil antibiotics for 3 months prior to study enrolment; no macrolide antibiotic for 12 months
Nil current illness
Ability to provide a consenting close cohabitant

Cohabitant defined as someone who has more than 4 hours of interaction with the index case on at least 5 days per week
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Smoking
Chronic lung disease including asthma if on corticosteroids
Use of any antibiotic within the preceding 3 months
Use of any Macrolide antibiotic within the preceding 12 months
Current use of any antibiotic
Respiratory tract illness within the preceding 1 month
current respiratory tract illness

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 will be recruited from the general community and randomised using a computer-generated randomisation sequence by the pharmacist. The patient and the investigating team are blinded to drug allocation. Both drugs look the same.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer-generated randomisation sequences, will be generated and held by the Mater Health services pharmacy department
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Multiplex endpoint PCR assay will be used to determine the presence of a panel of resistance genes as described in Malhotra Kumar
Quantification of bacterial resistance genes
Multiplex endpoint PCR assay will be used to determine the presence of a panel of resistance genes (erm(A), erm(B), mef, tet(M), tet(O), tet(K), tet(L) as described in Malhotra-Kumar.
Where resistant genes are detected; gene specific qPCR assays will be used to determine their abundance relative to total bacterial load. This will be determined by 16srRNA gene qPCR as previously detailed in Rogers GB et al
Microbiota composition analysis
Oropharyngeal swabs will undergo DNA extraction, followed by paired-read 16S-rRNA gene V1-V3 amplicon sequencing, using the illumine MISeq platform as per Rogers GB et al
Subsequent data analysis will utilize the following principles: Bray Curtis dissimilarity matrices will be generated based on microbiota profiles from visit 1, 2 and 3 samples. Distribution of microbiota similarity will be visualized by nonmetric multidimensional scaling (NMS) and the existence of significant between group differences tested by PERMANOVA test. Specifically assessment will be made on whether significant differences exist in microbiota composition between azithromycin or erythromycin groups at each timepoint. Where significant variances occur, SIMPER analysis will be used to determine the contribution to observed subgroup differences in microbiota composition by determining individual bacterial taxa as described in Rogers GB et al. . Significance of these taxon-level differences will be tested based on relative abundance variation (Mann Whitney U Test).

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
31/03/2017
Actual
Date of last participant enrolment
Anticipated
31/03/2017
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 4139 0
Mater Adult Hospital - South Brisbane
Recruitment postcode(s) [1] 10070 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 291796 0
Hospital
Name [1] 291796 0
Mater misericordiae Ltd
Country [1] 291796 0
Australia
Primary sponsor type
Hospital
Name
Mater misericordiae Ltd, South Brisbane
Address
Raymond Terrace
Aubigny Place
South Brisbane QLD 4101
Country
Australia
Secondary sponsor category [1] 290573 0
None
Name [1] 290573 0
Address [1] 290573 0
Country [1] 290573 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293312 0
Mater Misericordiae Ltd. Human Research Committee
Ethics committee address [1] 293312 0
Level 2, Aubigny Place
Raymond Terrace
South Brisbane, QLD 4101
Ethics committee country [1] 293312 0
Australia
Date submitted for ethics approval [1] 293312 0
Approval date [1] 293312 0
21/05/2015
Ethics approval number [1] 293312 0
HREC/15/MHS/41

Summary
Brief summary
to determine whether in normal healthy volunteers without recent antibiotic exposure, one month of daily erythromycin treatment will induce lower rates of macrolide resistance in commensal oropharyngeal flora than one month of daily azithromycin
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 59350 0
Dr Lucy Burr
Address 59350 0
Mater Research
Respiratory Research Unit
Level 3, Aubigny Place
Raymond Terrace
South Brisbane QLD 4101
Country 59350 0
Australia
Phone 59350 0
+61 7 3163 2128
Fax 59350 0
+61 7 3163 8519
Email 59350 0
[email protected]
Contact person for public queries
Name 59351 0
Megan Martin
Address 59351 0
Mater Research
Respiratory Research Unit
level 3, Aubigny Place
Raymond Terrace
South Brisbane QLD 4101
Country 59351 0
Australia
Phone 59351 0
+61 7 3163 2128
Fax 59351 0
+61 7 3163 8519
Email 59351 0
[email protected]
Contact person for scientific queries
Name 59352 0
Lucy Burr
Address 59352 0
Mater Research
Respiratory Research Unit
Level 3, Aubigny place
raymond Terrace
South Brisbane QLD 4101
Country 59352 0
Australia
Phone 59352 0
+61 7 3163 2128
Fax 59352 0
+61 7 3163 8519
Email 59352 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
SourceTitleYear of PublicationDOI
EmbaseAssessment of Long-Term Macrolide Exposure on the Oropharyngeal Microbiome and Macrolide Resistance in Healthy Adults and Consequences for Onward Transmission of Resistance.2022https://dx.doi.org/10.1128/aac.02246-21
EmbaseThe Impact of Long-Term Macrolide Exposure on the Gut Microbiome and Its Implications for Metabolic Control.2023https://dx.doi.org/10.1128/spectrum.00831-23
N.B. These documents automatically identified may not have been verified by the study sponsor.