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Trial registered on ANZCTR


Registration number
ACTRN12618000436279
Ethics application status
Approved
Date submitted
6/03/2018
Date registered
26/03/2018
Date last updated
26/03/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Perioperative care in chronic sinusitis
Scientific title
Drug distribution and impact on the bacterial microbiome in chronic rhinosinusitis (CRS)
Secondary ID [1] 294244 0
None
Universal Trial Number (UTN)
U1111-1204-4072
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic rhinosinusitis 306923 0
Condition category
Condition code
Inflammatory and Immune System 306020 306020 0 0
Other inflammatory or immune system disorders
Infection 306021 306021 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients presenting for the first time into the rhinology clinic with chronic sinusitis. Patients will receive one of four oral medications for 7 days along with other standard medical treatment. Doxycyline, roxythromycin, augmentin or prednisone
1) doxycycline 100mg tablet twice daily (DOXY group) (7 days)
2) augmentin 625mg three times daily (AUG group) (7 days)
3) roxithromycin 300mg once daily (ROX group) (7 days)
4) prednisone 30mg once daily (PRED group) (7 days)

To monitor adherence - patients asked to keep a diary, will also look at drug tablet return
Intervention code [1] 300541 0
Treatment: Drugs
Comparator / control treatment
6 patients not receiving any oral treatment. As with other patients receiving oral treatment, they will receive other routinely prescribed treatments which are given longer term, period based on clinical need according to BMJ Best Medical Practice guideline - topical corticosteroid nasal spray (100mcg fluticasone proprionate 100mcg twice a day, and sinus rinses up to 6 times a day)
Control group
Active

Outcomes
Primary outcome [1] 305054 0
Stool microbiology
Analysis performed using 16s rRNA profiling
Timepoint [1] 305054 0
Stool samples will be collected by all patients at the beginning of the one-week medication period (baseline) and after the one-week period.

Primary outcome [2] 305055 0
Nasal mucous microbiology
Analysis performed using 16s rRNA profiling
Timepoint [2] 305055 0
Nasal swabs are taken from CRS patients attending the specialist rhinology clinic at Auckland Hospital. The swabs taken before taking medication (baseline) and immediately after medical therapy (after one-week period) will be compared.
Primary outcome [3] 305056 0
Drug concentrations in nasal mucus
The concentrations of all medications will be measured in the nasal mucus using validated high-performance liquid chromatographic HPLC methods.
This is in order to evaluate the trend over time which we will the compare with trends in drug concentration at other sites (stool, plasma). will also compare data against the known pharmacokinetic profiles of the specific drug
Timepoint [3] 305056 0
Nasal mucous samples are collected for patients in all patients in clinic at Auckland Hospital twice; once at the beginning of the medication period (patient has started taking medicine) and once following medication period, at scheduled clinic appointments.
Secondary outcome [1] 344252 0
Stool/gastrointestinal secondary outcomes:
1) cytokine assay profile (exploratory outcome)
An array of several inflammatory cytokines including IL-4, IL-5, IL-6, IL-10, and IL-13 will be measured in the stool of the patients using a cytokine ELISA.
Timepoint [1] 344252 0
Stool samples will be collected by all patients at the beginning of the one-week medication period (baseline) and after the one-week period.
Secondary outcome [2] 344259 0
Nasal swab/nasal secondary outcomes:
2) nasal mucus cytokine assay profile (exploratory outcome)
An array of several inflammatory cytokines including IL-4, IL-5, IL-6, IL-10, and IL13 will be measured in the mucus of the patients using a cytokine ELISA.
Timepoint [2] 344259 0
Nasal swabs are taken from CRS patients attending the specialist rhinology clinic at Auckland Hospital. The swabs taken before taking medication (baseline) and immediately after medical therapy (after one-week period) will be compared.
Secondary outcome [3] 344383 0
Fourth primary endpoint:
Drug concentrations in stool
The concentrations of all medications will be measured in the stool using validated high-performance liquid chromatographic HPLC methods.
This is in order to evaluate the trend over time which we will the compare with trends in drug concentration at other sites (nasal mucus, plasma). will also compare data against the known pharmacokinetic profiles of the specific drug
Timepoint [3] 344383 0
Stool samples will be collected by all patients at the beginning of the one-week medication period (baseline) and after the one-week period.
Secondary outcome [4] 344386 0
Fifth primary endpoint:
Drug concentrations in plasma
The concentrations of all medications will be measured in plasma filtrate using validated high-performance liquid chromatographic HPLC methods.
This is in order to evaluate the trend over time which we will the compare with trends in drug concentration at other sites (nasal mucus, stool). will also compare data against the known pharmacokinetic profiles of the specific drug
Timepoint [4] 344386 0
Blood samples are collected for patients in all patients in clinic at Auckland Hospital twice; once at the beginning of the medication period (patient has started taking medicine) and once following medication period, at scheduled clinic appointments.
Secondary outcome [5] 344387 0
Further stool/gastrointestinal secondary outcomes (exploratory):
2) stool major basic protein analysis
Exploratory outcome: intend to use a major basic protein ELISA to observe if any changes occur with use of medical therapies.
Timepoint [5] 344387 0
Stool samples will be collected by all patients at the beginning of the one-week medication period (baseline) and after the one-week period.
Secondary outcome [6] 344388 0
Further stool/gastrointestinal secondary outcomes:
3) stool pH
pH measured using pH indicator
Timepoint [6] 344388 0
Stool samples will be collected by all patients at the beginning of the one-week medication period (baseline) and after the one-week period.
Secondary outcome [7] 344389 0
Further stool/gastrointestinal secondary outcomes:
4) Patient reported gastrointestinal symptom scores (Gastrointestinal Symptom Rating Scale).
Timepoint [7] 344389 0
Scores collected for all patients at the beginning of the one-week medication period (baseline) and after the one-week period.
Secondary outcome [8] 344390 0
Further Nasal swab/nasal secondary outcomes (exploratory):
2) nasal mucus major basic protein analysis
Exploratory outcome: intend to use a major basic protein ELISA to observe if any changes occur with use of medical therapies.
Timepoint [8] 344390 0
Nasal swabs are taken from CRS patients attending the specialist rhinology clinic at Auckland Hospital. The swabs taken before taking medication (baseline) and immediately after medical therapy (after one-week period) will be compared.
Secondary outcome [9] 344391 0
Further Nasal swab/nasal secondary outcomes:
3) nasal mucus pH.
pH measured using pH indicator
Timepoint [9] 344391 0
Nasal swabs are taken from CRS patients attending the specialist rhinology clinic at Auckland Hospital. The swabs taken before taking medication (baseline) and immediately after medical therapy (after one-week period) will be compared.
Secondary outcome [10] 344392 0
Further Nasal swab/nasal secondary outcomes:
4) patient reported symptom scores (Sinonasal Outcome Test – 5)
Timepoint [10] 344392 0
Scores collected before taking medication (baseline) and immediately after medical therapy (after one-week period).
Secondary outcome [11] 344684 0
Further Nasal swab/nasal secondary outcomes:
5) Endoscopic scoring (Lund-Kennedy Endoscopic Score).
Timepoint [11] 344684 0
Scores collected before taking medication (baseline) and immediately after medical therapy (after one-week period).

Eligibility
Key inclusion criteria
Inclusion Criteria

Patients diagnosed with CRS.
Patients providing fully informed consent to participate in this study.
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

Patients who are acutely unwell.
Patients with cystic fibrosis.
Patients with a history of previous nasal surgery.
Children (<16 years)
Immunodeficiency (congenital or acquired)
Congenital mucociliary problems (e.g. primary ciliary dyskinesia)
Non-invasive and invasive fungal sinus disease
Systemic vasculitis and granulomatous diseases
Chronic gastrointestinal inflammatory or immune-mediated diseases
History of cocaine abuse;
Patients requiring sinus surgery for neoplasia
Patients unable to consent (e.g. lack of mental capacity)
Patients on oral antibiotics or systemic corticosteroids in the four weeks prior to recruitment
Patients with known allergies to the 4 medications

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)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
16/04/2018
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
46
Accrual to date
Final
Recruitment outside Australia
Country [1] 9652 0
New Zealand
State/province [1] 9652 0

Funding & Sponsors
Funding source category [1] 298883 0
Charities/Societies/Foundations
Name [1] 298883 0
Garnett Passe and Rodney Williams foundation
Country [1] 298883 0
Australia
Primary sponsor type
Individual
Name
Dr Joey Siu
Address
Department of Surgery
University of Auckland
Private Bag 92019
Auckland Mail Centre 1142
Country
New Zealand
Secondary sponsor category [1] 298099 0
None
Name [1] 298099 0
Address [1] 298099 0
Country [1] 298099 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299825 0
Health and Disability Ethics Committee
Ethics committee address [1] 299825 0
Ethics committee country [1] 299825 0
New Zealand
Date submitted for ethics approval [1] 299825 0
Approval date [1] 299825 0
14/02/2018
Ethics approval number [1] 299825 0

Summary
Brief summary
In summary, the main aim of this study is to investigate the drug concentration of routine peri-operative care medication (antibiotics and oral steroids) in the nasal mucus and stool in relation to changes in the nasal and gut microbiome respectively. We anticipate that better understanding of the effects of our current medical management, including their adverse effects, will help in the future to develop and deliver more targeted therapy to our patients.



Study Aims

The overall goal of this study is to extend our previous research in the effects of perioperative medication on the nasal microbiome in patients with chronic sinusitis (CRS) 14/NTA/134 by investigating changes in the nasal and gut microbiome with additional commonly used antibiotics and steroids and how they relate to drug distribution.

Study aim 1. The aim of this pilot study is to investigate the effects of routine peri-operative care medication (antibiotics and oral steroids), on:
1a. the gut microbiome and gastrointestinal side effects of patients with chronic sinusitis.
1b. changes in the nasal microbiome and inflammatory cytokines.
1c. elucidate any patterns in drug distribution at specific body sites (nose, gut) and any relationships between the pharmacokinetic profiles of the medication in these sites
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 81686 0
A/Prof Richard Douglas
Address 81686 0
Department of Surgery
University of Auckland
Private Bag 92019
Auckland Mail Centre 1142
Country 81686 0
New Zealand
Phone 81686 0
+6427 218 6083
Fax 81686 0
Email 81686 0
[email protected]
Contact person for public queries
Name 81687 0
Joey Siu
Address 81687 0
Department of Surgery
University of Auckland
Private Bag 92019
Auckland Mail Centre 1142
Country 81687 0
New Zealand
Phone 81687 0
+64210505499
Fax 81687 0
Email 81687 0
[email protected]
Contact person for scientific queries
Name 81688 0
Joey Siu
Address 81688 0
Department of Surgery
University of Auckland
Private Bag 92019
Auckland Mail Centre 1142
Country 81688 0
New Zealand
Phone 81688 0
+64210505499
Fax 81688 0
Email 81688 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
EmbaseOral antibiotics used in the treatment of chronic rhinosinusitis have limited penetration into the sinonasal mucosa: a randomized trial.2020https://dx.doi.org/10.1080/00498254.2020.1814973
EmbaseSinonasal and gastrointestinal bacterial composition and abundance are stable after 1 week of once-daily oral antibiotic treatment for chronic rhinosinusitis.2021https://dx.doi.org/10.1002/alr.22799
N.B. These documents automatically identified may not have been verified by the study sponsor.