Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12609001079235
Ethics application status
Approved
Date submitted
4/12/2009
Date registered
16/12/2009
Date last updated
12/11/2018
Date data sharing statement initially provided
12/11/2018
Date results information initially provided
12/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised controlled study comparing the effect of two different anticoagulation regimens on filter life during Continuous Renal Replacement Therapy (CRRT) – The Heparin Citrate (THC) Study
Scientific title
A randomised controlled trial comparing the effect on filter life of regional citrate anticoagulation vs regional heparin anticoagulation in critically ill adults requiring continuous renal replacement therapy
Secondary ID [1] 1204 0
None
Universal Trial Number (UTN)
Trial acronym
THC study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
acute renal failure 252346 0
Condition category
Condition code
Renal and Urogenital 252537 252537 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Regional citrate anticoagulation of a continuous renal replacement therapy circuit. Fluids containing citrate are infused into extracorporeal venous blood pre-blood pump to achieve a final concentration of approximately 3mmol/L (this is the anticoagulant dose). This causes hypocalcaemia and anticoagulation. The patient is prevented from becoming hypocalcaemic by the use of a systemic calcium infusion (hence the anticoagulation is only in one region of the circuit). The citrate is infused continuously during treatment with renal replacement therapy and lasts for the duration of the renal replacement therapy.
Intervention code [1] 255659 0
Treatment: Drugs
Comparator / control treatment
Regional heparin anticoagulation of a continuous renal replacement therapy circuit using protamine reversal. Heparin is infused into extracorporeal venous blood pre-blood pump at a rate of 1500 units/hour. The patient is prevented from becoming systemically anticoagulated by the infusion of protamine 15 mg/h intot the return limb of the circuit (hence the anticoagulation is only in one region of the circuit). The heparin and protamine is infused continuously during treatment with renal replacement therapy and lasts for the duration of the renal replacement therapy.
Control group
Active

Outcomes
Primary outcome [1] 253420 0
functional filter life. The functional life of
the filter will be determined to be over when the circuit has clotted defined by the presence of one of the following: a) the transmembrane pressure across the filter is greater than 300 mmHg, b) there is visible clot in the circuit obstructing blood flow, c) the blood pump is unable to rotate due to obstruction by clot in the membrane or circuit. The end of the functional filter life will be determined by intensive care nursing staff not associated with the running of the trial.
Timepoint [1] 253420 0
time to event in hours
Secondary outcome [1] 262527 0
cytokines. Serum will be frozen and batch analysed later for interleukins 6, 8 and 10 (at least).
Timepoint [1] 262527 0
0, 24, 72 hours
Secondary outcome [2] 262528 0
Units of red cells transfused. This will be determined from the blood bank transfusion record of administered packed red cells..
Timepoint [2] 262528 0
Count. This is defined as the number of packed red cells administered during the entire intensive care unit (ICU) admission.
Secondary outcome [3] 262529 0
duration of continuous renal replacement therapy (CRRT)
Timepoint [3] 262529 0
time in hours. This is measured at the final conclusion of the continuous renal replacement therapy (CRRT). CRRT may finally conclude upon recovery of renal function, discharge from ICU, or commencement of intermittent haemodialysis.
Secondary outcome [4] 262530 0
duration of ICU admission
Timepoint [4] 262530 0
time in hours. This is measured from the time of admission to the intensive care unit until the time of discharge from the intensive care unit.
Secondary outcome [5] 262531 0
mortality
Timepoint [5] 262531 0
at hospital discharge

Eligibility
Key inclusion criteria
All must apply: a) the treating clinician believes that the patient requires CRRT for acute renal failure, b) the clinician is uncertain about the balance of benefits and risks likely to be conferred by treatment with citrate/calcium or heparin/protamine, d) informed consent has been obtained, or will be sought within 48h in those centres where delayed consent has been approved, e) the patient fulfils ONE of the following clinical criteria for initiating CRRT: (i) oliguria (urine output < 100ml/6hr) that has been unresponsive to fluid resuscitation measures. (ii) hyperkalemia ([K+] > 6.5 mmol/L), (iii) severe acidemia (pH < 7.2), (iv) urea > 25 mmol/L., (v) Creatinine >300 micromol/L, (vi) clinically significant organ oedema in the setting of acute renal failure (ARF) (eg: lung).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Any one may apply: a) expected short stay ICU (< 24hours), b) Age < 18 years, c) Acute or chronic liver failure, d) suspected ischaemic hepatitis, e) known allergy to protamine or heparin, f) suspected or confirmed heparin-induced thrombocytopenia, g) there is a
strong likelihood that the study treatment would not be continued in accordance with the study protocol

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)
Treatment allocation will be concealed by the use of sealed, opaque, sequentially numbered envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
permuted block randomisation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
It is not possible to blind treatment allocation
Phase
Phase 3 / Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
28/01/2010
Actual
28/01/2010
Date of last participant enrolment
Anticipated
12/01/2013
Actual
12/01/2013
Date of last data collection
Anticipated
Actual
31/01/2013
Sample size
Target
220
Accrual to date
Final
212
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment outside Australia
Country [1] 6973 0
New Zealand
State/province [1] 6973 0

Funding & Sponsors
Funding source category [1] 256137 0
Charities/Societies/Foundations
Name [1] 256137 0
Intensive Care Foundation
Country [1] 256137 0
Australia
Funding source category [2] 256138 0
Charities/Societies/Foundations
Name [2] 256138 0
Austin ICU Research Fund
Country [2] 256138 0
Australia
Primary sponsor type
Hospital
Name
Royal Prince Alfred Hospital
Address
Intensive Care Services
Royal Prince Alfred Hospital
Missenden Rd
Camperdown NSW 2050
Country
Australia
Secondary sponsor category [1] 251477 0
Hospital
Name [1] 251477 0
Austin Hospital
Address [1] 251477 0
Intensive Care Unit
Austin Hospital
145 Studley Rd
Heidelberg VIC 3084
Country [1] 251477 0
Australia
Secondary sponsor category [2] 251478 0
Hospital
Name [2] 251478 0
Royal North Shore Hospital
Address [2] 251478 0
Intensive Care Unit
Royal North Shore Hospital
Pacific Highway
St Leonards NSW 2065
Country [2] 251478 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 258228 0
Sydney South West Area Health Services Human Research Ethics Committee (HREC)
Ethics committee address [1] 258228 0
Royal Prince Alfred Hospital
c/- Research Development Office
Missenden Rd
Camperdown NSW 2050
Ethics committee country [1] 258228 0
Australia
Date submitted for ethics approval [1] 258228 0
Approval date [1] 258228 0
12/05/2009
Ethics approval number [1] 258228 0

Summary
Brief summary
The hypothesis that this trial will test is that the citrate/calcium approach for
regional anticoagulation is more effective than the heparin/protamine method at maintaining functional filter life in patients receiving continuous renal replacement therapy (CRRT). CRRT is the form of dialysis that is used in the intensive care unit for critically ill patients. Blood is removed from the patients body and circulated through a membrane before being returned. This circuit outside the body causes the blood to start clotting unless a drug is used to prevent this happening. We will compare two different methods of preventing this clotting to see which one can prevent the blood clotting for the longer time. Prevention of blood clotting in the circuit is desirable because of the interruptions in treatment that this causes.
Trial website
Trial related presentations / publications
06/04/2015 Gattas DJ, Rajbhandari D, Bradford C, Buhr H, Lo S, Bellomo R. A Randomized Controlled Trial of Regional Citrate Versus Regional Heparin Anticoagulation for Continuous Renal Replacement Therapy in Critically Ill Adults. Crit Care Med. 2015 Apr 6. [Epub ahead of print] PubMed PMID: 25853591
Public notes

Contacts
Principal investigator
Name 30585 0
A/Prof David Gattas
Address 30585 0
c/- Intensive Care Services
Royal Prince Alfred Hospital
Missenden Rd
Camperdown
NSW 2050
Country 30585 0
Australia
Phone 30585 0
+61295155436
Fax 30585 0
Email 30585 0
[email protected]
Contact person for public queries
Name 13832 0
A/Prof David Gattas
Address 13832 0
Intensive Care Services
Royal Prince Alfred Hospital
Missenden Rd
Camperdown NSW 2050
Country 13832 0
Australia
Phone 13832 0
+61295155436
Fax 13832 0
Email 13832 0
[email protected]
Contact person for scientific queries
Name 4760 0
A/Prof David Gattas
Address 4760 0
Intensive Care Services
Royal Prince Alfred Hospital
Missenden Rd
Camperdown NSW 2050
Country 4760 0
Australia
Phone 4760 0
+61295155436
Fax 4760 0
Email 4760 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
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
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Gattas DJ, Rajbhandari D, Bradford C, Buhr H, Lo S... [More Details]
Plain language summaryNo Regional citrate and calcium anticoagulation prolo... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseA randomized controlled trial of regional citrate versus regional heparin anticoagulation for continuous renal replacement therapy in critically ill adults.2015https://dx.doi.org/10.1097/CCM.0000000000001004
N.B. These documents automatically identified may not have been verified by the study sponsor.