Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12616000657426
Ethics application status
Approved
Date submitted
29/04/2016
Date registered
20/05/2016
Date last updated
28/04/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Percutaneous cannulation of the thoracic duct in acute pancreatitis to achieve external lymph drainage
Scientific title
Developing and evaluating techniques for peripheral transvenous cannulation of the
thoracic duct to study the role of lymph in acute pancreatitis and critical illness
Secondary ID [1] 289112 0
Nil known
Universal Trial Number (UTN)
U1111-1175-6314
Trial acronym
PerCTD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Pancreatitis 298580 0
Condition category
Condition code
Oral and Gastrointestinal 298658 298658 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 298825 298825 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a method development study comprised of two sequential phases. The second phase is dependent on the success of the first.
Phase 1: Inguinal lymphangiogram performed by a consultant interventional radiologist. 6 patients with acute pancreatitis exhibiting a SIRS response will be recruited and consented. Using a sterile technique under local anaesthetic and ultrasound guidance an inguinal lymph node will be injected with 3-6mL of iodized oil. Fluoroscopy will then be used to identify opacification of the thoracic duct and its junction with the venous system. Optimal timing of this opacification will also be assessed. This is expected to take up to 2.5 hours. The volume of contrast and number of lymph nodes injected may need to be varied to improve the fidelity of this project depending on initial results.

Phase 2: Inguinal lymphangiogram, percutaneous thoracic duct cannulation and external drainage of thoracic duct lymph performed by a consultant interventional radiologist.
12 patients with acute pancreatitis exhibiting a SIRS response will be recruited and consented. Patients in this phase will receive all three interventions immediately after each other provided that the proceeding intervention is successful.
Intervention 1: An inguinal lymphangiogram (developed in Phase 1) will be used to visualise the thoracic duct. Success of the inguinal lymphangiogram in identifying whether the junction of the thoracic duct with the venous system is suitable for cannulation will be determined by the interventional radiologist performing the procedure.

Intervention 2: Under a sterile technique and ultrasound guidance the venous system will be accessed from the left antecubital fossa in a manner similar to a PICC line. Thoracic duct cannulation will be attempted from the subclavian vein using standard interventional radiology techniques, guided by lymphangiography and confirmed by the aspiration of lymph. A Pruitt type balloon catheter (or similar) will be placed to simultaneously occlude the thoracic duct and achieve external lymph drainage. Interventions 1 & 2 are expected to take up to 2.5 hours. Intervention 2 will only occur if intervention 1 is successful. This will be determined by the successful aspiration of lymph from the thoracic duct catheter. The guide wires and catheters used may need to be varied to improve the success of this intervention.

Intervention 3: The thoracic duct catheter will be connected to a biliary drainage bag to facilitate external thoracic duct lymph drainage for 7 days while the patient is in hospital. Matched peripheral plasma samples will be taken 12 hourly. The volume of lymph drained will be replaced mL:mL with either Plasmalyte or 4% albumin. SIRS, APACHE II and modified Marshall scores along with daily CRP will be recorded to assess patient response to external lymph drainage. Intervention 3 will only occur if interventions 1 & 2 are successful.. If the thoracic duct catheter stops draining lymph before the end of 7 days regular (12 hourly hep saline (50IU in 3mL) flushes will be trialled to maintain patency.
Intervention code [1] 294616 0
Treatment: Other
Intervention code [2] 294767 0
Treatment: Surgery
Comparator / control treatment
No control.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 298153 0
Successful aspiration of lymph from catheter placed in the thoracic duct.

When the interventional radiologist believes the thoracic duct catheter has been correctly placed in the thoracic duct under fluoroscopic visualisation this will be confirmed by attaching a 5mL syringe to the end of the thoracic duct catheter. If lymph is aspirated this will confirm the correct placement of the catheter.
Timepoint [1] 298153 0
Aspiration of lymph at time of attempted thoracic duct cannulation.
Secondary outcome [1] 323288 0
Achieving 7 days of continual lymph drainage from the thoracic duct catheter without occlusion of the catheter. Occlusion will be assessed with firstly with heparinized saline flushing and if it does not resolve with contrast fluoroscopy.
Timepoint [1] 323288 0
7 days following cannulation if continual lymph drainage achieved
Time following cannulation that catheter becomes occluded.
Secondary outcome [2] 323289 0
Change in SIRS score from recruitment until the end of 7 days
Timepoint [2] 323289 0
7 days following cannulation
Secondary outcome [3] 323290 0
Change in APACHE II score from recruitment to the end of 7 days
Timepoint [3] 323290 0
7 days following cannulation
Secondary outcome [4] 323291 0
The change in serum CRP level will be calculated by subtracting the CRP level at 7 days following cannulation from the CRP on day of cannulation.
Timepoint [4] 323291 0
7 days following cannulation
Secondary outcome [5] 323292 0
Change in Modified Marshall score from recruitment until the end of 7 days.
Timepoint [5] 323292 0
7 days following cannulation

Eligibility
Key inclusion criteria
Project 1: Patients over 40 with acute pancreatitis admitted to Auckland City Hospital.

Project 2: Patients over 18 with acute pancreatitis exhibiting a SIRS response within 24 hours of admission to Auckland City Hospital.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
*Pregnancy
*Concurrent MODS
*Requirement for either a central venous catheter or PICC line prior to thoracic duct cannulation
*Coagulopathy
*Patients actively bleeding
*Previous thoracic duct injury, intervention or ligation
*Previous left neck dissection
*Previous groin dissection
*Any skin or subcutaneous infection in the groin or antecubital fossa
*Previous deep vein thrombosis or pulmonary embolism
*Platelet count greater than 800
*Concurrent malignancy
*Previous mastectomy or axillary node dissection to the same side as proposed cannulation

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
N/A
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
This study is a method development study comprised of two sequential projects, hence no randomisation. The first project with 6 patients will develop the inguinal lympangiogram procedure to identify the junction of the thoracic duct with the venous system. The second project will use the inguinal lymphangiogram technique to identify the thoracic duct and attempt to cannulate it. If this is successful lymph will be drained externally for 1 week.
Phase
Not Applicable
Type of endpoint/s
Safety
Statistical methods / analysis
This study is designed to develop a methodology rather than to assess efficacy. The sample sizes for projects 1 and 2 were determined on clinical grounds taking into account anatomical variability and disease severity to develop the methodology of percutaneous thoracic duct cannulation before it is formally evaluated in an appropriately powered RCT.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/09/2016
Actual
Date of last participant enrolment
Anticipated
31/12/2018
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
18
Accrual to date
Final
Recruitment outside Australia
Country [1] 7844 0
New Zealand
State/province [1] 7844 0
Auckland

Funding & Sponsors
Funding source category [1] 293485 0
Charities/Societies/Foundations
Name [1] 293485 0
Maurice and Phyllis Paykel Trust
Country [1] 293485 0
New Zealand
Primary sponsor type
University
Name
The University of Auckland
Address
Research Office
Level 10
49 Symonds Street
Private Bag 92019
Auckland Mail Centre 1142
Country
New Zealand
Secondary sponsor category [1] 292307 0
None
Name [1] 292307 0
Address [1] 292307 0
Country [1] 292307 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294928 0
Northern A Health and Disability Ethics Committee
Ethics committee address [1] 294928 0
Health and Disability Ethics Committees
Ministry of Health
Freyberg Building
20 Aitken Street
PO Box 5013
Wellington 6011
Ethics committee country [1] 294928 0
New Zealand
Date submitted for ethics approval [1] 294928 0
24/03/2016
Approval date [1] 294928 0
28/04/2016
Ethics approval number [1] 294928 0
16/NTA/35

Summary
Brief summary
Abstract
Background
The systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) are features of critical illness that result from a range of aetiologies including trauma, sepsis, haemorrhagic shock and acute pancreatitis. Persistent organ failure is the most common cause of mortality in critical illness. Experimental evidence indicates that gut-lymph draining via the thoracic duct drives SIRS and MODS. Human studies (to confirm the toxicity of thoracic duct lymph in critical illness, analyse its composition and to develop lymph targeted treatments) have been hampered by the inability to easily and reliably access thoracic duct lymph.

Aim
The aims of this study are
i) to optimise the technique of thoracic duct lymphangiography
ii) to develop and evaluate a safe, percutaneous, peripheral and transvenous technique of thoracic duct cannulation
iii) to determine the composition of human thoracic duct lymph and matched plasma samples during acute pancreatitis
iv) to identify factors responsible for toxicity of human thoracic duct lymph

Methods
This application contains three projects in patients with acute pancreatitis.
The first project (n=6) will confirm the technical feasibility and time required to achieve an optimal thoracic duct lymphangiogram by ultrasound guided contrast injection of an inguinal lymph node.
The second project (n=12) will refine and develop the technique of peripheral transvenous cannulation of the thoracic duct (PTCTD).
The third project will use the thoracic duct lymph collected from patients during the course of the second project to determine the composition and toxicity of the lymph using established laboratory assay platforms. The composition of matched lymph and plasma will also be compared as part of this study.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 65514 0
Prof John Windsor
Address 65514 0
Department of Surgery
The University of Auckland
Private Bag 92019
Auckland Mail Centre 1142
Country 65514 0
New Zealand
Phone 65514 0
+64 21 901 930
Fax 65514 0
Email 65514 0
[email protected]
Contact person for public queries
Name 65515 0
Prof John Windsor
Address 65515 0
Department of Surgery
The University of Auckland
Private Bag 92019
Auckland Mail Centre 1142
Country 65515 0
New Zealand
Phone 65515 0
+64 21 901 930
Fax 65515 0
Email 65515 0
[email protected]
Contact person for scientific queries
Name 65516 0
Prof John Windsor
Address 65516 0
Department of Surgery
The University of Auckland
Private Bag 92019
Auckland Mail Centre 1142
Country 65516 0
New Zealand
Phone 65516 0
+64 21 901 930
Fax 65516 0
Email 65516 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
No additional documents have been identified.