Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617000412336
Ethics application status
Approved
Date submitted
16/02/2017
Date registered
22/03/2017
Date last updated
17/10/2022
Date data sharing statement initially provided
28/05/2019
Date results provided
25/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Impact of Compression Therapy on Cellulitis
Scientific title
Impact of Compression Therapy on Cellulitis (ICTOC) in adults with chronic oedema: a randomised controlled trial
Secondary ID [1] 291158 0
Nil known
Universal Trial Number (UTN)
Trial acronym
ICTOC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lower Limb Recurrent Cellulitis 302018 0
Lower limb Chronic Oedema 302019 0
Condition category
Condition code
Infection 301658 301658 0 0
Studies of infection and infectious agents
Cardiovascular 301659 301659 0 0
Diseases of the vasculature and circulation including the lymphatic system
Cardiovascular 302098 302098 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants in the control and intervention groups will receive education regarding cellulitis prevention at an initial appointment. The initial appointment will take approximately 60-90minutes and will be conducted in individual format. Education will involve a handout (created for the study) and verbal education regarding how to maintain good skin integrity and prevent infection through good skin care (moisturising regularly, minimising trauma to skin (long pants, closed shoes, insect repellent, sunscreen etc), managing minor wounds/abrasions/bites (using antiseptic creams and covering with dressings), minimising risk of tinea/fungal infections between toes (dry between toes, thongs in public pools/showers) and managing inflammatory skin conditions).
The intervention group will be provided with the same education but the initial appointment will also be used to plan appropriate compression therapy, which will then be provided in subsequent additional appointments. The treatment plan will be developed by a qualified level 1 lymphoedema physiotherapist based on the participants' requirements (e.g severity of swelling, functional capacity, and ability to do/doff compression garments). Compression therapy will consist of prescription of appropriate compression garments and where indicated provision of a period of compression bandaging to minimise swelling prior to measure for and fit of compression garments). The number of appointments necessary for provision of compression therapy will vary based on patient requirements. Patients may require between 1-6 appointments per episode of care and appointments may range from 30-90 minutes. Time per appointment and number of appointments will vary based on the severity of oedema (patients with more severe oedema will require more compression bandages to reduce oedema), patient function and comorbidities, and number of legs affected). Compression garments will be selected from the current range available on the Australian market and may include ready to wear or custom made garments, including wrap systems. The initial garments provided to the patient free of charge will be from Haddenham Health Care, who have a range of ready to wear and custom made garments which are available on the Australian market.
Following this, participants in both groups will be followed for up to three years at regular intervals (6 monthly) to have outcomes measures taken and to continue to receive the allocated treatment (cellulitis prevention education with or without compression therapy). Compression garments with or without bandaging will be renewed regularly (every 6-12 months).

- Clinicians who providing chronic oedema management and education to prevent cellulitis will be qualified level 1 Lymphoedema physiotherapists

- Participants will be seen at Calvary Public Hospital Bruce outpatient physiotherapy department

Assessments will be done face to face where possible. Phone interview may be used to find out the primary outcome. QOL tools may be mailed to the participant if required.

-Compliance with treatment will be monitored at regular assessments (by self report)
Intervention code [1] 297150 0
Prevention
Intervention code [2] 297151 0
Treatment: Devices
Comparator / control treatment
Participants in the control group will receive only education (regarding the benefits of skin care and how to prevent cellulitis through prevention of tinea/fungal infections between toes) compared to the intervention group who will receive both education and compression.

Note: For patients in the control group, once an episode of cellulitis has occurred, they will cross-over into the intervention group to receive compression therapy.
Control group
Active

Outcomes
Primary outcome [1] 301107 0
Time to first episode of recurrent cellulitis (days) Diagnosis of cellulitis will be identified through patient report and confirmed through medical record review or from General practitioner report when deemed necessary by the clinician
Timepoint [1] 301107 0
Time to first episode of recurrent cellulitis (days) Diagnosis of cellulitis will be identified through participant report and confirmed through medical record review or from General practitioner report when deemed necessary by the clinician
Secondary outcome [1] 331749 0
Time to cellulitis-related hospital admissions;

Hospitalisation will be gained by participant self report and confirmed through medical record review or from General practitioner report.
Timepoint [1] 331749 0
Assessed 6 monthly for three years from initial assessment.
Secondary outcome [2] 370900 0
Change in leg volume (% and mm). Perometer will be used to assess leg volume. Tape measure will be used as a back-up measure for leg circumferences.
Timepoint [2] 370900 0
Volume assessed at initial assessment, post initial treatment and then 6monthly from initial assessment for three years. Assessment of volume post initial treatment will occur when compression garments are initially fitted. Fitting of garments may or may not be preceded by a period of compression bandaging to decrease oedema.
Secondary outcome [3] 370901 0

Quality of life using LYMQOL and EQ-5D-3L questionnaires
Timepoint [3] 370901 0
LYMQOL and eq-5d will be completed at initial assessment and then 6, 12, 24 and 36 months post intervention.

Eligibility
Key inclusion criteria
1. The patients is over 18 years of age
2. The patient is identified as having chronic oedema (oedema persisting more than 3 months) in one or both legs
3. The patient has a history of 2 or more episodes of cellulitis in the past 2 years
4. The patient is able to understand their involvement in the study, as per the information sheet
5.The patient is able to give informed consent
6. The patient has a valid Medicare card
7. The patient is able to attend regular scheduled appointments
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. The patient is currently receiving chronic oedema management that involves compression
2. The patient declines to participate or is unable to participate for whatever reason
3. The patient is receiving end of life care
4. The patient is medically unstable
5.The patient has wounds requiring treatment that prevents use of compression garments
6. The patient is unable to wear compression (unable to don/doff garments or has a medical condition that contraindicates use of compression)

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)
sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation using a randomisation table created by
computer software (i.e. computerised sequence generation)

As prophylactic antibiotics may strongly influence recurrence of cellulitis (Morton & Swartz, 2004), randomisation of participants will be stratified by prophylactic antibiotic use
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
For patients in the control group, once an episode of cellulitis has occurred, they will cross-over into the intervention group to receive compression therapy. Follow up will continue according to the original specified plan (6 monthly from initial assessment)
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size and duration of follow up
The sample size has been calculated for the primary objective of detecting a difference in time to cellulitis recurrence between the control and intervention groups. The sample size estimation is based upon the assumptions that the 3-year cellulitis recurrence rate in control participants is approximately 47% and compression therapy will reduce the 3-year incidence of recurrent cellulitis by 50%.. Assuming that events occur at a constant rate, these assumptions correspond to a hazard ratio of 0.42. The eligibility criteria of two or more episodes of cellulitis in the same leg in the past 2 years has been used so that the trial cohort have an increased likelihood of cellulitis reoccurring during the follow up period.

It is assumed that patients will be recruited over a 2.5-year period, and the total study duration will be 3.5 years. Length of participant follow up will vary based on time of enrolment. Using a sequential design software package gsDesign in R29, in order to detect a hazard ratio of 0.42 with 80% power and 2.5% (1-sided) type 1 error, a total of 45 cellulitis recurrences are needed. Under the present recruitment and recurrence assumptions, we plan to recruit 162 participants (81 per arm).

An interim analysis will be performed by a Data Monitoring Committee after 23 episodes of cellulitis. A log rank test will be used to assess group differences. If a nominal (1 sided) significance level of p=0.003 is detected, indicating a strong clinical effect, the study will be ceased. If the Data Monitoring Committee recommends that the study continue to 45 episodes of cellulitis, the final analysis will use a log rank test with (1-sided) significance level p=0.0238. These efficacy bounds were derived using a Hwang-Shih-DeCani spending function with gamma = -4 to preserve an overall Type I error rate of 5%.

Proposed methods for data analysis
For the main outcome measure of ‘time to first episode of recurrent cellulitis’ and the secondary outcome of 'time to cellulitis-related hospital admission', survival analysis will be undertaken. Kaplan-Meier plots will be used to visualise patterns of time to first cellulitis recurrence between the groups, with a log rank test being used to determine if there is a statistically significant difference between the groups. Cox proportional hazards regression may also be used to adjust for important risk factors. Right censoring will be used for participants who are lost to follow up. Intention to treat analysis will be used, with all enrolled participants being assessed according to their randomisation, regardless of protocol adherence.

For the secondary outcomes of percent change in limb volume and QOL, measures will be taken at multiple time points. Therefore, groups will be compared using a linear mixed model or using a repeated measures analysis. There will be no adjustment for multiplicity.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
After the interim analysis in March this year, the trial met the specified stopping criteria and therefore recruitment was ceased and all participants in the control group were provided with compression.
Date of first participant enrolment
Anticipated
1/04/2017
Actual
2/06/2017
Date of last participant enrolment
Anticipated
31/12/2019
Actual
25/01/2019
Date of last data collection
Anticipated
31/12/2022
Actual
17/12/2020
Sample size
Target
162
Accrual to date
Final
84
Recruitment in Australia
Recruitment state(s)
ACT
Recruitment hospital [1] 7492 0
Calvary Public Hospital ACT - Bruce
Recruitment hospital [2] 7493 0
The Canberra Hospital - Garran
Recruitment postcode(s) [1] 15317 0
2617 - Bruce
Recruitment postcode(s) [2] 15318 0
2605 - Garran

Funding & Sponsors
Funding source category [1] 295596 0
Hospital
Name [1] 295596 0
Calvary Public Hopsital Bruce
Country [1] 295596 0
Australia
Funding source category [2] 295632 0
Commercial sector/Industry
Name [2] 295632 0
Haddenham Healthcare
Country [2] 295632 0
Australia
Primary sponsor type
Hospital
Name
Calvary Public Hospital Bruce
Address
Calvary Public Hospital Bruce,
Haydon Drive,
Bruce
ACT 2617
Country
Australia
Secondary sponsor category [1] 294428 0
None
Name [1] 294428 0
Address [1] 294428 0
Country [1] 294428 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296917 0
Calvary Public Hospital Human Research Ethics Committee
Ethics committee address [1] 296917 0
Ethics committee country [1] 296917 0
Australia
Date submitted for ethics approval [1] 296917 0
23/11/2016
Approval date [1] 296917 0
17/01/2017
Ethics approval number [1] 296917 0
Ethics committee name [2] 298146 0
ACT Health Human Research Ethics Committee
Ethics committee address [2] 298146 0
Ethics committee country [2] 298146 0
Australia
Date submitted for ethics approval [2] 298146 0
13/04/2017
Approval date [2] 298146 0
18/05/2017
Ethics approval number [2] 298146 0
ETH.4.17.092

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

Contacts
Principal investigator
Name 72426 0
Ms Elizabeth Webb
Address 72426 0
Calvary Public Hospital
Haydon Drive
Bruce
ACT 2617
Country 72426 0
Australia
Phone 72426 0
+61 412 959 294 and +61 2 6201 6190
Fax 72426 0
Email 72426 0
[email protected]
Contact person for public queries
Name 72427 0
Elizabeth Webb
Address 72427 0
Calvary Public Hospital
Haydon Drive
Bruce
ACT 2617
Country 72427 0
Australia
Phone 72427 0
+61 412 959 294 and +61 2 6201 6190
Fax 72427 0
Email 72427 0
[email protected]
Contact person for scientific queries
Name 72428 0
Elizabeth Webb
Address 72428 0
Calvary Public Hospital
Haydon Drive
Bruce
ACT 2617
Country 72428 0
Australia
Phone 72428 0
+61 412 959 294 and +61 2 6201 6190
Fax 72428 0
Email 72428 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


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
EmbaseImpact of Compression Therapy on Cellulitis (ICTOC) in adults with chronic oedema: A randomised controlled trial protocol.2019https://dx.doi.org/10.1136/bmjopen-2019-029225
EmbaseCompression therapy to prevent recurrent cellulitis of the leg.2020https://dx.doi.org/10.1056/NEJMoa1917197
N.B. These documents automatically identified may not have been verified by the study sponsor.