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Trial registered on ANZCTR


Registration number
ACTRN12618000957291
Ethics application status
Approved
Date submitted
2/06/2018
Date registered
6/06/2018
Date last updated
6/06/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
The clinical efficacy of non-surgical periodontal debridement alone, adjunctive systemic azithromycin, or amoxicillin-metronidazole therapy in patients with chronic moderate-to-advanced periodontitis
Scientific title
Comparing the periodontal tissue response to non-surgical scaling and root planing alone, adjunctive azithromycin, or adjunctive amoxicillin plus metronidazole in generalised chronic moderate-to-severe periodontitis: a preliminary randomised controlled trial.
Secondary ID [1] 294973 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Periodontitis 307972 0
Condition category
Condition code
Oral and Gastrointestinal 307010 307010 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1: Ultrasonic and manual full-mouth scaling and root planing (2 x 90 min sessions within 7 days) alone.
Arm 2: Ultrasonic and manual full-mouth scaling and root planing (2 x 90 min sessions within 7 days), plus amoxicillin 500mg and metronidazole 400mg, three times a day for seven days; administered via oral tablets.
Arm 3: Ultrasonic and manual full-mouth scaling and root planing (2 x 90 min sessions within 7 days), plus azithromycin 500mg once a day for three days; administered via oral tablet.

The intervention drugs were administered by a third party clinician (dental hygienist) with no involvement in the study. Adherence and any adverse events were reported by the patient via an anonymous written survey given out at 1 week follow-up.
Intervention code [1] 301299 0
Treatment: Drugs
Intervention code [2] 301440 0
Treatment: Other
Comparator / control treatment
The control group (Arm 1) received ultrasonic and manual full-mouth scaling and root planing over two appointments, within 7 days, without any adjuncts
Control group
Active

Outcomes
Primary outcome [1] 306011 0
Median difference in full-mouth clinical attachment level (CAL) using a Hu-Friedy Colourvue periodontal probe.
Timepoint [1] 306011 0
Measured prior to commencement of intervention and 2-months (primary timepoint) following commencement of intervention.
Secondary outcome [1] 347300 0
Differences between the three treatment arms for median number of residual sites with probing pocket depth greater than or equal to 5mm post-treatment using a Hu-Friedy Colourvue periodontal probe.
Timepoint [1] 347300 0
Measured prior to commencement of intervention and 2-months following commencement of intervention.
Secondary outcome [2] 347301 0
Differences between the three treatment arms for probing pocket depth (PPD) at baseline PPD sites with slight (3-4mm), moderate (5-6mm) and severe disease (greater than 6mm).
Measured using a Hu-Friedy Colourvue periodontal probe.
Timepoint [2] 347301 0
Measured prior to commencement of intervention and 2-months following commencement of intervention.
Secondary outcome [3] 347302 0
Median difference in full-mouth probing pocket depth using a Hu-Friedy Colourvue periodontal probe.
Timepoint [3] 347302 0
Measured prior to commencement of intervention and 2-months following commencement of intervention.
Secondary outcome [4] 347305 0
Median difference in full-mouth bleeding on probing using a Hu-Friedy Colourvue periodontal probe.
Timepoint [4] 347305 0
Measured prior to commencement of intervention and 2-months following commencement of intervention.
Secondary outcome [5] 347306 0
Median difference in inflammatory cytokine concentrations (interleukin-8, interleukin-1beta).
Inflammatory cytokine concentrations were measured by collecting samples of gingival crevicular fluid, using PerioPaper strips. These were stored and later analysed using CBA human inflammatory cytokines kit (BD Biosciences, San Jose, CA) and cytometric bead assay.
Timepoint [5] 347306 0
Measured prior to commencement of intervention, 1 week after commencement of intervention, and 2-months following commencement of intervention.
Secondary outcome [6] 347753 0
Differences between the three treatment arms for clinical attachment level changes at baseline PPD sites with slight (3-4mm), moderate (5-6mm) and severe disease (greater than 6mm).
Measured using a Hu-Friedy Colourvue periodontal probe.
Timepoint [6] 347753 0
Measured prior to commencement of intervention and 2-months following commencement of intervention.

Eligibility
Key inclusion criteria
All patients were in good general health and were diagnosed with generalised moderate-to-severe chronic periodontitis based on the current classification of the American Academy of Periodontology:
* At least 16 natural teeth (excluding third molars and teeth with advanced caries indicated for extraction).
* More than 30% of teeth probing pocket depth greater than or equal to 5mm, clinical attachment level greater than or equal to 3mm, and bleeding on probing at baseline.
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Pregnancy and lactation.
* Active tobacco smoking.
* Scaling and root planing or antibiotic therapy within the last six months.
* Medical disorders that require prophylactic antibiotic coverage or that could influence the progression or treatment of periodontitis
* Long term administration of anti-inflammatory or immunosuppressive medications
* Positive history of cardiovascular disease
* Known hypersensitivity to amoxicillin, metronidazole or amoxicillin.

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)
To preserve allocation concealment, the randomisation coordinator marked the code number and allocated treatment on a card which was sealed in an opaque envelope. The coded envelopes were given to a third-party clinician, with no involvement in the study, who dispensed the allocated antibiotics to patients following scaling and root planing. All study personnel were blinded to treatment assignment, which was successfully retained throughout the entire duration of the study.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Each of the selected patients were assigned consecutive, ascending numbers, as well as a code number, at the enrolment appointment. Before the beginning of scaling and root planing, the randomisation coordinator used a computerised random number generator to formulate the allocation sequence to randomly assign patients to one of three therapeutic groups. This was executed using block randomisation and an allocation ratio of 1:1:1 (mixed block size of 39, 2 blocks). The generated randomisation list was kept by the randomization coordinator until all treatment, follow-up visits and statistical analyses were performed, and was inaccessible to the examiner/treating clinician.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?

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 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
For descriptive analysis of categorical data, absolute and relative frequencies were calculated. Numerical data was first assessed for approximate normality. All numerical variables in the data set were skewed and thereby described using median, interquartile range, and range. Chi-square tests and Kruskal-Wallis tests were used for inferential analysis comparing patients’, teeth, and all outcome characteristics at baseline.

For each time point, median full-mouth bleeding on probing, probing pocket depth and clinical attachment level, number of residual sites with probing pocket depth greater than or equal to 5 mm post-treatment, and interleukin-1beta and interleukin-8 levels, were calculated for each patient and then averaged across patients in each treatment group. The overall probing pocket depth reduction and clinical attachment level gain observed at follow-up for full-mouth values and strata based on initial slight, moderate and deep sites, were determined by averaging the data at each time point within a patient and subtracting the 2-month data from the baseline data. These subtracted values were then averaged across patients in each of the three groups.

Differences from baseline to follow-up for all outcome variables between the three treatment groups were compared using Kruskal-Wallis tests. If significant differences were found, Mann-Whitney U tests were used for pairwise post-hoc comparisons between two treatment groups at a time.

The significance of differences from baseline to follow-up in each treatment group for each clinical parameter was conducted using non-parametric Wilcoxon signed rank tests. The significance of differences in interleukin-1beta and interleukin-8 levels over time (baseline, 1-week post-therapy and 2-month post-therapy) among treatment groups were sought using non-parametric Friedman tests, followed by post-hoc Wilcoxon signed rank tests. The level of significance was set at P less than 0.05.

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
Actual
6/07/2016
Date of last participant enrolment
Anticipated
Actual
17/05/2017
Date of last data collection
Anticipated
Actual
12/07/2017
Sample size
Target
78
Accrual to date
Final
38
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 11011 0
JCU Dental Clinic - Smithfield
Recruitment postcode(s) [1] 22793 0
4878 - Smithfield

Funding & Sponsors
Funding source category [1] 299562 0
Charities/Societies/Foundations
Name [1] 299562 0
Australian Dental Research Foundation
Country [1] 299562 0
Australia
Funding source category [2] 299591 0
University
Name [2] 299591 0
James Cook University
Country [2] 299591 0
Australia
Primary sponsor type
Individual
Name
Andrew Liaw
Address
School of Medicine and Dentistry
James Cook University
14-88 McGregor Rd, Smithfield QLD 4878
Country
Australia
Secondary sponsor category [1] 298870 0
None
Name [1] 298870 0
Address [1] 298870 0
Country [1] 298870 0
Other collaborator category [1] 280127 0
Individual
Name [1] 280127 0
Kate Miller
Address [1] 280127 0
School of Medicine and Dentistry
James Cook University
14-88 McGregor Rd, Smithfield QLD 4878
Country [1] 280127 0
Australia
Other collaborator category [2] 280128 0
Individual
Name [2] 280128 0
Alan Nimmo
Address [2] 280128 0
School of Medicine and Dentistry
James Cook University
14-88 McGregor Rd, Smithfield QLD 4878
Country [2] 280128 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300459 0
James Cook University Human Research Ethics Committee
Ethics committee address [1] 300459 0
Ethics committee country [1] 300459 0
Australia
Date submitted for ethics approval [1] 300459 0
10/05/2016
Approval date [1] 300459 0
17/05/2016
Ethics approval number [1] 300459 0
H6501

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

Contacts
Principal investigator
Name 83730 0
Dr Andrew Liaw
Address 83730 0
School of Medicine and Dentistry
James Cook University
14-88 McGregor Rd, Smithfield QLD 4878
Country 83730 0
Australia
Phone 83730 0
+61 7 4232 1300
Fax 83730 0
Email 83730 0
andrew.liaw@my.jcu.edu.au
Contact person for public queries
Name 83731 0
Andrew Liaw
Address 83731 0
School of Medicine and Dentistry
James Cook University
1/14-88 McGregor Rd, Smithfield QLD 4878
Country 83731 0
Australia
Phone 83731 0
+61 7 4232 1300
Fax 83731 0
Email 83731 0
andrew.liaw@my.jcu.edu.au
Contact person for scientific queries
Name 83732 0
Andrew Liaw
Address 83732 0
School of Medicine and Dentistry
James Cook University
14-88 McGregor Rd, Smithfield QLD 4878
Country 83732 0
Australia
Phone 83732 0
+61 7 4232 1300
Fax 83732 0
Email 83732 0
andrew.liaw@my.jcu.edu.au

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.