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Trial registered on ANZCTR


Registration number
ACTRN12614001125617
Ethics application status
Approved
Date submitted
10/10/2014
Date registered
23/10/2014
Date last updated
29/03/2021
Date data sharing statement initially provided
19/06/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Treatment efficacy of azithromycin 1g versus seven days doxycycline for the treatment of rectal chlamydia among men who have sex with men – a double-blind randomized controlled trial
Scientific title
Treatment efficacy of azithromycin 1g versus seven days doxycycline (100mg twice a day) for the treatment of rectal chlamydia among men who have sex with men – a double-blind randomized controlled trial
Secondary ID [1] 285430 0
NIL
Universal Trial Number (UTN)
NIL
Trial acronym
RTS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chlamydia trachomatis 293189 0
Condition category
Condition code
Infection 293464 293464 0 0
Sexually transmitted infections

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Oral azithromycin 1g single dose plus oral placebo doxycycline twice a day for 7 days (with the first dose of placebo doxycycline taken at the same time as the azithromycin dose)

OR

Oral doxycycline 100mg twice a day for 7 day plus oral placebo azithromycin single dose (with the placebo dose of azithromycin taken at the same time as the first doxycycline dose)

Compliance will be measured by answering a text message at end of week 1 about drug adherence. They will be also asked to return the pill bottle for pill count as a proxy measure of drug compliance at the conclusion of the trial.
Intervention code [1] 290356 0
Treatment: Drugs
Comparator / control treatment
Azithromycin 1g single dose plus placebo doxycycline twice a day for 7 days OR

Doxycycline 100mg twice a day for 7 day plus placebo azithromycin single dose

The comparator drug will be the active doxycycline, relative to active azithromycin.

Placebo oral tablets will be composed of all/some of inert ingredients found in their corresponding active tablets such as microcrystalline cellulose, silica, maize starch, magnesium stearate or titanium dioxide for the azithromycin or doxycycline placebo tablets.
Control group
Active

Outcomes
Primary outcome [1] 293283 0
Treatment efficacy/microbial cure at 4 weeks after recruitment. Microbial cure is defined as a negative chlamydia PCR test result performed on a rectal swab. (NB: For the purpose of this trial, microbial cure will be used as a measure of treatment efficacy.)
Timepoint [1] 293283 0
4 weeks post recruitment
Secondary outcome [1] 310713 0
Adjusted microbial cure at 4 weeks: We will use whole genome sequencing and mRNA tests to help us differentiate between re-infection, treatment failure and a false positive diagnosis for any cases diagnosed chlamydia PCR positive at week 4
Timepoint [1] 310713 0
4 weeks post recruitment

Eligibility
Key inclusion criteria
Consecutive English-speaking men aged 16 years or older, with rectal chlamydia meeting the eligibility criteria will be recruited and followed up for 4 weeks.

Inclusion criteria
* Men who report male to male sexual contact and are aged 16 years or older who test positive for rectal chlamydia using a Nucleic Acid Amplification Test (NAAT).
* Adequate English and comprehension skills to give informed consent
Minimum age
16 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Men will be excluded:
i. they present with proctitis/other symptoms.
ii. are concurrently diagnosed with another bacterial STI
iii. Self-reported use of antibiotics in the last 2 weeks
iv. Known contraindications to the use of azithromycin or doxycycline including allergy

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Eligible men will be approached by a research nurse and invited to participate in the trial. The nurse will explain the trial, assess eligibility and collect informed consent. Eligible men will be enrolled and randomly assigned to either 1g single dose azithromycin or seven day (100mg twice daily) doxycycline. Participants will complete a brief questionnaire and undergo a routine sexual health examination during which a nurse will teach participants to take self-collected rectal swab samples for further analysis. Once participants are randomly allocated to a treatment group, the nurse will directly observe him taking his first dose of treatment
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computer-generated randomisation 1:1 block-10 randomisation sequence will be created by an independent statistician.

Blinded therapy will be labelled with individual kit numbers. Study drugs will be packaged into individually numbered kits stored by independent site pharmacists. The effectiveness of blinding will be tested at completion of the trial when participants will be asked to indicate which treatment they thought they had received. Both medications will be packaged identically to maintain blinding.
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
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The primary analysis will be a modified-intention-to-treat analysis (m-ITT) which includes all who commenced randomised therapy, provided a specimen for test-of-cure and did not have an LGV genovar at recruitment. We will compare the proportions with microbiological cure based on the clinic’s pathology NAAT-result and calculate the difference in proportions and 95% confidence intervals using the predictive margins function of logistic regression.


Sample size: Our hypothesis is that azithromycin efficacy will be less than that of doxycycline. We will recruit 700 men in total (350 in each group) which allowing for a 20% loss to follow up (based on our experience of other similar cohort studies of MSM). Sample size calculations were based on detecting a 5% difference between doxycycline and azithromycin microbial cure at 4 weeks with 80% power and a 6% difference with 90% power. If microbial cure is 96% among those treated with doxycycline at 4 weeks, then we will have 80% to detect a 6% difference and 90% power to detect a 7% difference.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/11/2015
Actual
12/08/2016
Date of last participant enrolment
Anticipated
30/12/2019
Actual
17/07/2019
Date of last data collection
Anticipated
16/07/2019
Actual
16/08/2019
Sample size
Target
700
Accrual to date
Final
625
Recruitment in Australia
Recruitment state(s)
SA
Recruitment postcode(s) [1] 8754 0
3053 - Carlton
Recruitment postcode(s) [2] 8755 0
2000 - Sydney
Recruitment postcode(s) [3] 23462 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 290036 0
Government body
Name [1] 290036 0
National Health and Medical Research Council (NHMRC) Program Grant
Country [1] 290036 0
Australia
Primary sponsor type
University
Name
University of Melbourne
Address
Level 3, 207 Bouverie st
Carlton South, Victoria, 3053
Country
Australia
Secondary sponsor category [1] 288727 0
None
Name [1] 288727 0
Address [1] 288727 0
Country [1] 288727 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291746 0
Alfred Health Human Ethics Committee
Ethics committee address [1] 291746 0
Alfred Hospital
55 Commercial Rd, Melbourne VIC 3004
Ethics committee country [1] 291746 0
Australia
Date submitted for ethics approval [1] 291746 0
01/07/2015
Approval date [1] 291746 0
04/09/2015
Ethics approval number [1] 291746 0
Ethics committee name [2] 291748 0
Southern Eastern Sydney Local Health District Human Research Ethics Committee (Southern Sector)
Ethics committee address [2] 291748 0
Level 13, Kolling Building (6)
Royal North Shore Hospital
Pacific Highway
ST LEONARDS NSW 2065
Ethics committee country [2] 291748 0
Australia
Date submitted for ethics approval [2] 291748 0
19/11/2014
Approval date [2] 291748 0
Ethics approval number [2] 291748 0

Summary
Brief summary
There are increasing concerns regarding the treatment efficacy of azithromycin 1g single dose for the treatment of rectal chlamydia infections with treatment failure rates up to 21% being reported.

There is no evidence available from randomised controlled trials directly comparing doxycycline with azithromycin for the treatment of rectal chlamydia with a recent meta-analysis reporting an efficacy of approximately 85% for azithromycin compared with 99% for doxycycline - however, these efficacy estimates are based on poor quality evidence.

The purpose of this study is to provide the world first evidence on the treatment efficacy of the two recommended treatments for rectal chlamydia - azithromycin 1g single dose versus 7 days of doxycycline (100mg twice a day)
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 51830 0
Prof Jane Hocking
Address 51830 0
University of Melbourne
Level 3, 207 Bouverie st
Carlton South 3053
Victoria, Australia
Country 51830 0
Australia
Phone 51830 0
+61 3 8344 0762
Fax 51830 0
+61 3 9349 5815
Email 51830 0
[email protected]
Contact person for public queries
Name 51831 0
Jane Hocking
Address 51831 0
University of Melbourne
Level 3, 207 Bouverie st
Carlton South 3053
Victoria, Australia
Country 51831 0
Australia
Phone 51831 0
+61 3 8344 0762
Fax 51831 0
+61 3 9349 5815
Email 51831 0
[email protected]
Contact person for scientific queries
Name 51832 0
Jane Hocking
Address 51832 0
University of Melbourne
Level 3, 207 Bouverie st
Carlton South 3053
Victoria, Australia
Country 51832 0
Australia
Phone 51832 0
+61 3 8344 0762
Fax 51832 0
+61 3 9349 5815
Email 51832 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
Only aggregated results will be presented.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
2386Study protocol    Published in BMC Infectious Diseases. 367193-(Uploaded-19-06-2019-13-00-37)-Study-related document.pdf



Results publications and other study-related documents

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

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseTreatment efficacy of azithromycin 1 g single dose versus doxycycline 100 mg twice daily for 7 days for the treatment of rectal chlamydia among men who have sex with men - a double-blind randomised controlled trial protocol.2017https://dx.doi.org/10.1186/s12879-016-2125-7
EmbaseAzithromycin or doxycycline for asymptomatic rectal chlamydia trachomatis.2021https://dx.doi.org/10.1056/NEJMoa2031631
N.B. These documents automatically identified may not have been verified by the study sponsor.