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Trial registered on ANZCTR


Registration number
ACTRN12615001353583
Ethics application status
Approved
Date submitted
9/12/2015
Date registered
14/12/2015
Date last updated
14/12/2015
Type of registration
Retrospectively registered

Titles & IDs
Public title
The impact of prescribed blood flow rate on circuit life in critically ill patients receiving continuous renal replacement therapy (CRRT) in intensive care
Scientific title
The impact of blood flow rate on circuit life in continuous renal replacement therapy (CRRT)
Secondary ID [1] 288110 0
N/A
Universal Trial Number (UTN)
Trial acronym
FORCE trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Kidney Injury 296978 0
Critical illness 296980 0
Condition category
Condition code
Renal and Urogenital 297234 297234 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This project sought to investigate the impact of blood flow rate on filter (circuit) life in patient’s treated with continuous renal replacement therapy (CRRT) - a type of artificial renal support in the intensive care unit (ICU). This study was a randomised controlled trial, conducted in a single tertiary centre, with a 20 bed ICU. Data was collected over one year duration with the intention of enrolling 100 critically ill patients diagnosed with acute kidney injury (AKI) and being treated with CRRT as part of their routine care.
Patients treated with CRRT as prescribed by the treating ICU physician would be randomised to either of two groups. The two intervention groups are a blood flow rate of 150 mL/min or 250 mL/min. Once allocated to either intervention the patients would remain allocated to that intervention arm for the duration of time they were treated with artificial renal support or CRRT in the ICU. The decision to cease CRRT therapy was at the sole discretion of the treating ICU physician. Patients who had had therapy ceased for native renal assessment but required re-intervention at a later time in the ICU would remain randomised into the intervention group allocated and treated with CCRT as instructed by the ICU physician.
The procedure for CRRT was standard as for all patients requiring renal support in the ICU. Devices or CRRT machines used were also those used in standard care for renal support. The machines used for this study were the Baxter Gambro Prismaflex and the Infomed HF440 haemofiltration machines.The therapy and the intervention are prescribed by the ICU physician and the practical application of the therapy and the intervention (blood flow rate)is administered by the bedside ICU nurse caring for the patient.
The outcome variable for the study was circuit life (hours before clotting of the blood filled circuit).

Intervention code [1] 293419 0
Treatment: Devices
Comparator / control treatment
Once the patient had been prescribed renal replacement therapy by the treating ICU physician , the patients were randomised to a set blood flow rate. The blood flow rate was either 150 ml/min or 250 mL/min. This range of blood flow is consistent with historical practice both in Australia and internationally. A difference of 100 ml/min was considered adequate to represent a meaningful difference in blood flow rate between the two groups while also reflecting current practice for this therapy. For the purposes of this study the control arm or usual care arm is the prescribed blood flow rate of 150 mL/min. The
Control group
Active

Outcomes
Primary outcome [1] 296816 0
Circuit life (the time in hours for the blood filled circuit used for artificial renal support or CRRT to clot and therfore the therapy to temporarily cease until the patient is disconnected from the clotted circuit and reconnected to a new therapy circuit)
Circuit life is recorded on a case report form by the bedside nurse as well as documenting on patients medical records by observation charts
Timepoint [1] 296816 0
Each blood filled circuit is considered to have a 'life' or time until eventual clotting. Each circuit will have different time points to clotting - this data is the variable of interest between the two groups. Information of the circuit life is collected by the bedside nurse and documented on the patients observation chart as part of the medical record. In addition the bedside nurse recorded the circuit life for each circuit and reasons for cessation on a prepared case report form (CRF). Data was collected by CRF on patient discharge from the ICU and verified using patients digital medical record after discharge for collation into data spreadsheet.
Secondary outcome [1] 319464 0
For each patient, there was assessment of the interventions for solute and waste product clearance. This was achieved by collecting the blood results taken as part of routine care. The blood test data collected were urea and creatinine and were obtained from the patients digital medical record after discharge form the ICU
Timepoint [1] 319464 0
The measurement of urea and creatinine are performed part of routine care and collected twice daily from the patient in the ICU.

Eligibility
Key inclusion criteria
Patients who have Developed AKI in accordance with the RIFLE classification (F) (grades of severity of AKI based on changes to serum creatinine and urine output and two clinical outcomes
Require Continuous Renal Replacement Therapy (CRRT) as prescribed by the treating intensive care physician
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who are anticipated to require a short stay in ICU; less than 24 hrs and or are expected to die in less than 24 hrs from ICU admission

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)
Central randomisation by web based randomisation service - off site at Griffith University in Brisbane, Queensland
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Stratified block randomisation will be the method of treatment allocation for this study. For this study blocks of four for a total of 100 participants in two groups
There are two forms of artificial renal support (CRRT) known as modes of therapy. They are called continuous venovenous haemofiltrtaion (CVVH) and continuous venovenous haemodiafiltration (CVVHDF)They vary slightly in their functional setup but are interchangeable for the treatment of AKI. Different ICUs will use one mode based on type of CRRT machine used or training. The randomisation were stratified to the mode of therapy CVVH or CVVHDF.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The sample was adult patients with AKI who required CRRT in the ICU. The sample was one of convenience, and although a single centre study, the patients were considered representitive of an adult intensive care population in a tertiary teaching facility in Australia. one hundred patients were enrolled in the study. This number was selected in order to ensure recruitment in a time period of one year. This study was considered a pilot and feasibility study as there was no there are no data to inform sample size using power calculations for this study. As a pilot study, the sample size has been considered to collect sufficient data to inform a power calculation and to identify issues relating to feasibility for a larger RCT

The study setting averages 138 patients requiring CRRT per year. A sample size of 100 would require recruitment of 72% of all patients needing CRRT in this ICU which should ensure achievability of enrolment. one hundred patients were randomised within the 12 month period.

Statistical analysis

The reason for cessation of treatment and circuit was recorded (elective or clotting). Elective cessation circuits would than be excluded from the circuit life analyses. The distribution of data for all circuits meeting the defined clotting criteria would be assessed. A frequency plot of circuit life for the two groups (150 mls/min vs. 250 mls/min) demonstrated that the study variables were not normally distributed and non-parametric descriptive statistics were used and circuit life reported as median and IQR. Circuit life for the two groups (150 mls/min vs. 250 mls/min) were compared using Mann-Whitney U-test.
Analysis of the two groups (150 mls/min vs. 250 mls/min) were then assessed for survival probability and presented graphically using Kaplan-Meier survival plots. A log-rank test was used to compare circuit life between the two groups. This analysis was not adjusted for any confounding variables.

All circuits (including those clotted and those electively removed) were then assessed. This analysis was a multi-stage process

1. Circuit life was analysed using repeated events survival analysis. A frailty model was used to test whether there is within subject dependence. As expected that there was heterogeneity among individual trial subjects. In addition individual trial subjects contributed one or multiple circuits. There may be a correlation between an individual trial subject contributing multiple circuits and circuit life.
As there may be something about the individual that has an unobserved influence on circuit life. The frailty model was therefore used to test event dependence (where the event is a clotted circuit) within the trial subjects. Event dependence in this study mean't that the occurrence of one event (time to clotting of the circuit) made further events (additional circuit clotting times) more or less likely. The advantage of this model is that it took into account any within-cluster correlation of circuit life.


2. The frailty model demonstrated that there was no within subject dependence, then analysis will be done using a proportional hazard conditional model (an extension of Cox regression). This method of analysis was used to study the effects of several risk factors (including blood flow rate) on circuit survival. Risk factors or confounding variables to circuit survival included mode of therapy (CVVH, CVVHDF), patients clotting profile, vascular access site and type, patients BMI, anticoagulation strategy etc). Proportions were compared using chi-square test and presented as a hazard ratio.

Assessment of solute control was achieved by delta urea and creatinine changes over 12 hour treatment times. The % change in both urea and creatinine as a measure of treatment efficiency was analysed using cox regression analysis including confounding variables of the patients mode of therapy (CVVH and CVVHDF), weight, BMI and Hb.
Solute clearance data is currently in the analysis stage with a biostatistician.

Recruitment
Recruitment status
Completed
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 in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 4873 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 12381 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 292527 0
Self funded/Unfunded
Name [1] 292527 0
N/A
Address [1] 292527 0
N/A
Country [1] 292527 0
Primary sponsor type
Individual
Name
Nigel Fealy
Address
C/- of Intensive care unit
Level 2, Austin Tower
Austin Health
145 Studley Rd
Heidelberg
3084
Country
Australia
Secondary sponsor category [1] 291237 0
None
Name [1] 291237 0
Address [1] 291237 0
Country [1] 291237 0
Other collaborator category [1] 278728 0
University
Name [1] 278728 0
Griffith University
Address [1] 278728 0
Centre for Health Practice Innovation
Room 0.01E
Health Science Building (N48)
Griffith University
170 Kessels Rd
NATHAN QLD 4111
Country [1] 278728 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294002 0
Human Research Ethics Committee (Austin Health)
Ethics committee address [1] 294002 0
145 Studley Rd
PO Box 5555
Heidelberg
Melbourne
Victoria
3084
Ethics committee country [1] 294002 0
Australia
Date submitted for ethics approval [1] 294002 0
10/10/2012
Approval date [1] 294002 0
01/11/2012
Ethics approval number [1] 294002 0
H2012/04772

Summary
Brief summary
Many patients admitted to the Intensive Care Unit (ICU) with a critical illness suffer from acute kidney injury. Acute kidney injury often requires the use of an artificial kidney therapy known as Continuous Renal Replacement Therapy (CRRT).

CRRT requires the establishment of a blood filled circuit (tubing) to enable the pumping of blood through an artificial kidney (also called a filter). This artificial kidney system often fails to work because blood clotting occurs. Ideally, this artificial kidney should function without clotting for at least 24 hours.

Some recent clinical observations and studies have suggested that premature clotting of the circuit may be due to interruption to blood flow by mechanical factors such as the position of the vascular access device, patient movement and positional changes. These mechanical factors cause reductions in blood flow or cessation of blood flow. This reduction in blood flow causes blood flow stasis promoting clot formation and eventual circuit failure.

There is great variability in the setting for the speed of the blood (blood flow rate) through the circuit amongst ICU’s in Australia. The blood flow rate may be influential in the promotion of clotting due to the mechanical factors described earlier. We proposed to make some comparisons between two blood flow rates (150 mL/min vs. 250 mL/min) currently being used within the ICU at Austin Health.

The aim of this audit is to prospectively collect information and identify any advantage (if any) of one particular blood flow rate setting over another.

This pilot and feasibility study completed data collection in Feb, 2015. Statistical analysis has required more advanced support than originally anticipated but is now complete. Only preliminary study results have been disseminated via presentation at the Annual Scientific Meeting of Intensive Care in Auckland.
Trial website
N/A
Trial related presentations / publications
Oral presentation at the 40th Annual Scientific Meeting of Intensive Care (ANZICS and ACCCN) in Auckland.29th - 31st October, 2015
Session: Free papers: Fluids and Renal (Sat 31st Oct)
Presentation: The impact of blood flow rate on circuit life in patients treated with CRRT.


Dissemination by Publication is currently in progress but has not been submitted to a journal to date.
Public notes

Contacts
Principal investigator
Name 62078 0
A/Prof Nigel Fealy
Address 62078 0
C/- of Intensive care unit
Level 2, Austin Tower
Austin Health
145 Studley Rd
Heidelberg
Melbourne
Victoria
3084
Country 62078 0
Australia
Phone 62078 0
61 3 9496 4834
Fax 62078 0
Email 62078 0
nigel.fealy@austin.org.au
Contact person for public queries
Name 62079 0
Prof Leanne Aitken
Address 62079 0
School of Nursing and Midwifery
Nathan Campus
Griffith University
Brisbane
Nursing Practice Development Unit,
Princess Alexandra Hospital,
Ipswich Road,
Woolloongabba QLD 4102

Country 62079 0
Australia
Phone 62079 0
+61 7 3176 7256;
Fax 62079 0
+61 7 3176 7356
Email 62079 0
l.aitken@griffith.edu.au
Contact person for scientific queries
Name 62080 0
Prof Rinaldo Bellomo
Address 62080 0

Austin Health
145 Studley Rd
Heidelberg
Melbourne
Victoria
3084
Country 62080 0
Australia
Phone 62080 0
61-3-9496 5992
Fax 62080 0
Email 62080 0
rinaldo.bellomo@austin.org.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary