Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000416190
Ethics application status
Approved
Date submitted
11/03/2019
Date registered
13/03/2019
Date last updated
24/01/2020
Date data sharing statement initially provided
13/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
HepFree Trial: a Study to Compare Five Different Ways of Providing Heparin-free Hemodialysis in Patients With High Risk of Bleeding
Scientific title
Hemodialysis without Systemic Anticoagulation: A Prospective Randomized Trial to Evaluate Five Strategies in Patients at High Risk of Bleeding
Secondary ID [1] 297697 0
Nil known
Universal Trial Number (UTN)
U1111-1229-8862
Trial acronym
HepFree Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Kidney Disease 311988 0
End-stage renal failure 312013 0
Hemodialysis 312014 0
Hemodiafiltration 312015 0
High risk of bleeding 312016 0
Condition category
Condition code
Renal and Urogenital 310555 310555 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Consecutive participants will be randomly allocated into five groups to receive different strategies of heparin-free dialysis treatment. There will be one control group and four "interventional" arms, as follows:
Arm 1: Hemodialysis with heparin-coated dialyser/lines (EVODIAL dialyser and HEPRAN lines)
Arm 2: Hemodialysis using a combination of heparin-coated dialyser/lines (EVODIAL dialyser and HEPRAN lines) and normal saline flushes (100 ml every 30 minutes throughout the whole treatment)
Arm 3: Hemodiafiltration with predilution which is a modality of hemodialysis that uses dialyzers of high permeability and replaces the fluid losses before the blood enters the dialyser.
Arm 4: Combination of hemodialfiltration with predilution and heparin-coated dialyser/lines (EVODIAL dialyser and HEPRAN lines)

In arm 3 as well as in the control group, dialysers and lines will be used as per standard practices in Metro North Hospital and Health Services (i.e., Elisio 21H dialyser and non-heparin grafted lines).

Participants will remain in the allocated group during a maximum of three consecutive heparin-free HD/HDF sessions, without any switch allowed between arms.

Intervention code [1] 313927 0
Treatment: Devices
Comparator / control treatment
Hemodialysis with intermittent saline flushes (100 ml per flush every 30 minutes during treatment)
Control group
Active

Outcomes
Primary outcome [1] 319414 0
successful completion of hemodialysis or hemodiafiltration without significant problems with blood clotting. Treatments will be considered successful when there is:
• No complete occlusion of air traps or dialyzer rendering dialysis impossible;
• No additional saline flushes to prevent clotting;
• No change of dialyzer or bloodlines because of clotting;
• No premature termination (early rinse-back) because of clotting.
Timepoint [1] 319414 0
4hr of hemodialysis
Secondary outcome [1] 368066 0
Follow-up of the clotting during each HD/HDF session. Clotting in the air traps will be assessed using the semi-quantitative scale
Timepoint [1] 368066 0
At each hour throughout the dialysis session,
Secondary outcome [2] 368067 0
To compare the online transmembrane pressure (TMP). This is a measure displayed by the dialysis machine and will be recorded by the assisting nurse.
Timepoint [2] 368067 0
Hourly throughout the treatment
Secondary outcome [3] 368068 0
To compare the dialysis adequacy (online KT/V). This is a measure automatically calculated by the dialysis machine and will be recorded by the assisting nurse.
Timepoint [3] 368068 0
Hourly throughout the treatment
Secondary outcome [4] 368069 0
The total volume of normal saline used throughout the dialysis session
Timepoint [4] 368069 0
This will be recorded by the assisting nurse in the participants' chart along with other dialysis details
Secondary outcome [5] 368070 0
Occurrence of adverse events (e.g., dyspnoea, nausea, hypotension and hypersensitivity reaction)
Timepoint [5] 368070 0
The assisting nurse will monitor participants' self-reported symptoms and perform physical examination hourly throughout the treatment
Secondary outcome [6] 368071 0
Direct equipment costs involved in each dialysis treatment
Timepoint [6] 368071 0
This will be calculated by the sum of costs related to equipments used in each treatment (such as dialysers, lines and normal saline vials)

Eligibility
Key inclusion criteria
• Individuals with end stage renal failure on maintenance HD or HDF for more than 3 months;
• In-centre dialysis; high risk of bleeding (at the discretion of the assisting renal physician);
• Native or graft arteriovenous fistula with blood flow at least 250 ml/min;
• Patients with a tunnelled catheter locked by heparin can be included in the study after removal of heparin and rinsing the catheter prior to starting the treatment;
• Minimum age of 18 years with no gender restriction.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Dialysis in the intensive care unit;
• Patients with acute kidney injury;
• Patients treated in single needle mode;
• Known heparin contraindication (e.g. heparin-induced thrombocytopenia type II);
• Patients requiring blood products;
• Patients receiving oral anticoagulants (including anti-vitamin K) (> 3 days since treatment stopped and/or normalized international normalized ratio will be allowed);
• Patients receiving a combination of anti-platelet agents (> 5 days since treatment stopping will be allowed);
• Patients currently on unfractioned (UFH) or low molecular weight heparin (LMWH) for treatment of deep vein thrombosis;
• Patients treated with UFH or LMWH to prevent deep vein thrombosis (24 hours since last dose of LMWH or 12 hours since last dose of UFH was allowed).
• Patients with laboratory markers of liver dysfunction (ALT and AST more than double of upper borderline lab value);
• Patients with known coagulopathy or haemostasis disorder (pathological value of prothrombin time and aPTT, and platelets less than 50,000/ul);
• Patients with the diagnosis of malignancy.

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)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a computerised sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Based on previous studies, the rates of primary outcomes were 67% with intermittent saline flushes, 37% with heparin-coated circuits, and 60% with predilutional HDF. Using a two-tailed z-test of proportions between two groups with 80% power and a 5% level of significance, a sample size of 40 treatments in each arm is sufficient to detect a significant difference of 30% between intermittent saline flushes and heparin adsorption, whereas a sample size of 73 treatments would detect a difference of 7% between intermittent saline flushes and predilutional HDF. To date, there is no available data on the efficacy of the above-mentioned strategies combined. Nevertheless, assuming an additive effect, the number of treatments needed for the three remaining groups would be less than 40.
All analyses will be performed using the SAS 9.2 software (SAS Institute, Cary, NC, USA). The significance level will be set to p<0.05, one-tailed for the primary objective, two-tailed for others. Continuous variables will be described as mean ± standard deviation for reader's convenience, and categoric ones as frequency and percentage.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
3/09/2019
Actual
28/10/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
200
Accrual to date
3
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 13361 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 25960 0
4029 - Herston

Funding & Sponsors
Funding source category [1] 302221 0
Charities/Societies/Foundations
Name [1] 302221 0
RBWH research foundation
Country [1] 302221 0
Australia
Primary sponsor type
Individual
Name
Pedro Henrique Franca Gois
Address
Nephrology Department - RBWH
Level 9
Butterfiled Street, Herston QLD 4029.
Country
Australia
Secondary sponsor category [1] 302070 0
Individual
Name [1] 302070 0
Dwarakanathan Ranganathan
Address [1] 302070 0
Nephrology Department - RBWH
Level 9
Butterfiled Street, Herston QLD 4029.
Country [1] 302070 0
Australia
Secondary sponsor category [2] 302071 0
Individual
Name [2] 302071 0
Helen Healy
Address [2] 302071 0
Nephrology Department - RBWH
Level 9
Butterfiled Street, Herston QLD 4029.
Country [2] 302071 0
Australia
Secondary sponsor category [3] 302072 0
Individual
Name [3] 302072 0
Sharad Ratanjee
Address [3] 302072 0
Nephrology Department - RBWH
Level 9
Butterfiled Street, Herston QLD 4029.
Country [3] 302072 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302900 0
RBWH - Human Research Ethics Committee
Ethics committee address [1] 302900 0
Level 7, Block 7
Royal Brisbane and Women’s Hospital
Butterfield Street, Herston, Qld 4029
Ethics committee country [1] 302900 0
Australia
Date submitted for ethics approval [1] 302900 0
03/04/2019
Approval date [1] 302900 0
21/05/2019
Ethics approval number [1] 302900 0
LNR/2019/QRBW/53240

Summary
Brief summary
Hemodialysis is life saving for patients with kidney failure. The contact of blood with an artificial environment may cause clots. Heparin is a substance that slows the formation of clots. However, this cannot be given to some patients who have high risk of bleeding. The aim of this research is to compare 5 different ways of providing heparin-free dialysis. These include intermittent saline flushes, artificial circuit coated with heparin, artificial circuit coated with heparin & intermittent saline flush, online predilution and predilution with coating of heparin. We aim to look at successful completion of dialysis without bleeding or clotting problems.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 91782 0
Dr Pedro Henrique Franca Gois
Address 91782 0
Nephrology Department - RBWH
Level 9
Butterfiled Street, Herston QLD 4029.
Country 91782 0
Australia
Phone 91782 0
+61 7 3646 8576
Fax 91782 0
+61 7 3646 8576
Email 91782 0
[email protected]
Contact person for public queries
Name 91783 0
Dr Pedro Henrique Franca Gois
Address 91783 0
Nephrology Department - RBWH
Level 9
Butterfiled Street, Herston QLD 4029.
Country 91783 0
Australia
Phone 91783 0
+61 7 3646 8576
Fax 91783 0
+61 7 3646 8576
Email 91783 0
[email protected]
Contact person for scientific queries
Name 91784 0
Dr Pedro Henrique Franca Gois
Address 91784 0
Nephrology Department - RBWH
Level 9
Butterfiled Street, Herston QLD 4029.
Country 91784 0
Australia
Phone 91784 0
+61 7 3646 8576
Fax 91784 0
+61 7 3646 8576
Email 91784 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
undecided about IPD sharing yet. Need to discuss with HREC first.


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.