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Trial registered on ANZCTR


Registration number
ACTRN12617000951358
Ethics application status
Approved
Date submitted
20/06/2017
Date registered
4/07/2017
Date last updated
18/01/2019
Date data sharing statement initially provided
18/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Lymph node grafting for breast cancer related lymphoedema
Scientific title
Lymph node grafting for upper limb lymphoedema following breast cancer treatment
Secondary ID [1] 292239 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record
ACTRN12613001116718 - Waikato Hospital (New Zealand) pilot study of lymph node grafting.

Health condition
Health condition(s) or problem(s) studied:
Lymphoedema 303741 0
Condition category
Condition code
Surgery 303112 303112 0 0
Surgical techniques
Cancer 303113 303113 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Lymph node grafting from groin to upper limb. This technique is carried out by trained Plastic and Breast Surgeons and involves an incision in the groin with removal of two lymph nodes under local anaesthetic. Lymph nodes are then grafted into the subcutaneous tissue of the elbow and wrist of the affected limb. Surgeons will have a minimum of five years experience. This surgery is carried out in one surgical procedure and takes approximately 60 minutes.
In this is a randomised controlled trial participants will be randomly assigned to;
• The control group (standard care): Will receive standard lymphoedema therapy alone. This includes self-administered massage, therapeutic exercise, use of a compression sleeve and skin/nail care; OR
• The intervention group: Will undergo lymph node grafting surgery as well as standard lymphoedema therapy.
Adherence to the intervention won't be assessed. Standard lymphoedema therapy provided by Waikato lymphoedema therapists will be standardised.
Intervention code [1] 298400 0
Treatment: Surgery
Comparator / control treatment
Standard lymphoedema therapy is the control: Usual treatment as carried out and instructed by a lymphoedema therapist (either physiotherapist or registered nurse lymphoedema therapist) and consists of self-administered massage, therapeutic exercise, use of a compression sleeve and skin/nail care.
Control group
Active

Outcomes
Primary outcome [1] 302492 0
Lymphoedema Volume (LV): Expressed as the inter-limb Truncal Cone Volume (TCV) difference and change (including percentage) from baseline. A clinically significant change will be taken as >10% or 80 ml reduction from baseline.
Timepoint [1] 302492 0
24 months
Secondary outcome [1] 336186 0
1) Bioimpedance: Lymphoedema Index (L-dex) score change from baseline. All participants will be assessed in person at six, 12 and 24 months by a research (registered) nurse. L-dex scores (and also bilateral arm and leg circumference measurements) will be taken at these time points.
Timepoint [1] 336186 0
Six, 12 and 24 months post surgery/post enrolment to trial
Secondary outcome [2] 336311 0
2) Requirement for compression therapy: Whether a compression garment is still required.
All participants will be assessed in person at six, 12 and 24 months by a research (registered) nurse.
Timepoint [2] 336311 0
Six, 12 and 24 months post surgery/post enrolment to trial
Secondary outcome [3] 336312 0
3) Self rated quality of life: SNAC Study Specific Scales score change from baseline. The minimum clinically important difference will be taken as a 10 point difference on the 150 point scale.

Timepoint [3] 336312 0
Six, 12 and 24 months post surgery/post enrolment to trial
Secondary outcome [4] 336313 0
4) Episodes of cellulitis: requiring antibiotic treatment. All participants will be assessed in person at six, 12 and 24 months by a research (registered) nurse. Participants in the surgery arm will also be followed up at one month post-operatively to assess for the presence of surgical morbidity. Note at some follow up appointments participants will also be assessed by a Surgeon e.g. at the one month post-operative visit, or when trial follow-up coincides with annual breast cancer follow-up, or as required.
Timepoint [4] 336313 0
Six, 12 and 24 months post surgery/post enrolment to trial
Secondary outcome [5] 336526 0
5) Early surgical morbidity: Assessed for; a) haematoma requiring operative evacuation; b) seroma requiring aspiration; c) superficial surgical site infection (as defined by the Australian Infection Control Association)
Timepoint [5] 336526 0
One month post surgery (for intervention group only)
Secondary outcome [6] 336527 0
6) Assessment of grafted lymph nodes. lymphoscintigraphy will be used to assess for: a) uptake/no uptake of grafted nodes; b) lymphatic transport index; c) lymphoscintigraphic classification of lymphoedema.
Timepoint [6] 336527 0
Six months post surgery.

Eligibility
Key inclusion criteria
1) Ipsilateral upper limb lymphoedema of severity stage one (but requiring the regular use of a compression garment) or stage two (ISL staging system).
2) Previously treated stage 1-3 breast cancer.
3) Undergone local standard lymphoedema therapy for at least three months prior to enrolment and continued participation with techniques.
4) Fit for operative procedure.
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Metastatic breast cancer; past history of other malignancy with potential lymphatic drainage to either axillae; BMI >40; current smoker; congestive heart failure; low serum albumin (<32g/L); poorly controlled diabetes (HbA1c > 70mm/L); steroid medication.

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)
Web based randomisation
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Single centre, randomised, controlled, parallel-group, pragmatic, phase two clinical trial.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 9004 0
New Zealand
State/province [1] 9004 0
Waikato

Funding & Sponsors
Funding source category [1] 296786 0
Charities/Societies/Foundations
Name [1] 296786 0
Cancer Society of New Zealand
Address [1] 296786 0
The Cancer Society of New Zealand Inc.
Level 6, Ranchhod Tower
39 The Terrace
PO Box 651
Wellington 6140
New Zealand
Country [1] 296786 0
New Zealand
Funding source category [2] 296788 0
Hospital
Name [2] 296788 0
Braemar Hospital
Address [2] 296788 0
24 Ohaupo Road
Hamilton 3204
Country [2] 296788 0
New Zealand
Primary sponsor type
Individual
Name
Mr Winston McEwan
Address
Alison Surgical Centre
66 Alison Street
Hamilton Lake
HAMILTON 3204
Country
New Zealand
Secondary sponsor category [1] 295769 0
Other
Name [1] 295769 0
Waikato District Health Board
Address [1] 295769 0
c/- Waikato Hospital
Pembroke Street
Private Bag 3200
Hamilton 3240
Country [1] 295769 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298010 0
New Zealand Health & Disability Ethics Committees
Ethics committee address [1] 298010 0
PO Box 2013
Lambton Quay
Wellington 6145
Ethics committee country [1] 298010 0
New Zealand
Date submitted for ethics approval [1] 298010 0
07/07/2017
Approval date [1] 298010 0
09/10/2017
Ethics approval number [1] 298010 0

Summary
Brief summary
Upper limb lymphoedema is a common and often distressing sequelae of breast cancer treatment. Reconstructive lymphatic microsurgery may be considered if conservative treatment fails but is highly specialised and expensive. This phase two, pragmatic, randomised controlled trial will compare a novel surgical technique; lymph node grafting (LNG) in addition to standard lymphoedema therapy, against standard lymphoedema therapy alone. Study participants will be those with residual stage one to two breast-cancer related lymphoedema despite initial treatment with standard lymphoedema therapy. The aim is to determine whether LNG plus standard lymphoedema therapy produces a greater reduction in lymphoedema volume (LV) and improved quality of life compared with the control group; standard lymphoedema therapy alone. A further aim is to demonstrate that LNG is a safe treatment, with acceptable surgical morbidity.
Trial website
Trial related presentations / publications
Travis EC, Shugg S, McEwan WM. Lymph node grafting in the treatment of upper limb lymphoedema: a clinical trial. ANZ J Surg. 2015;85(9):631-5. (Pilot study publication)
Public notes

Contacts
Principal investigator
Name 75722 0
Mr Winston McEwan
Address 75722 0
Alison Surgical Centre
66 Alison Street
Hamilton Lake
HAMILTON 3204
Country 75722 0
New Zealand
Phone 75722 0
+64 21 259 3989
Fax 75722 0
+64 7 8343657
Email 75722 0
winst@clear.net.nz
Contact person for public queries
Name 75723 0
Ms Jenni Scarlet
Address 75723 0
Breast Cancer Research Office
Hockin Building
Waikato Hospital
Private Bag 3200
Hamilton 3240
Country 75723 0
New Zealand
Phone 75723 0
+64 7 8398726 Ext 97916
Fax 75723 0
+64 7 8343657
Email 75723 0
Jenni.Scarlet@waikatodhb.health.nz
Contact person for scientific queries
Name 75724 0
Dr Melissa Edwards
Address 75724 0
Breast Cancer Research Office
Hockin Building
Waikato Hospital
Private Bag 3200
Hamilton 3240
Country 75724 0
New Zealand
Phone 75724 0
+64 8 8398726 Ext 97842
Fax 75724 0
+64 78343657
Email 75724 0
Melissa.Edwards@waikatodhb.health.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
IPD availability would be dependent on who was requesting access to this.
A patient information/consent form is available to potential study participants (after introduction by a study team member).
A clinical study report will be available post study when analysis is completed.
What supporting documents are/will be available?
No other documents available
Summary results
Not applicable