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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]

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

Critical illness

Condition category

Condition code

Renal and Urogenital

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]

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]

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]

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]

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]

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

Sex

Both males and females

Can healthy volunteers participate?

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

24/06/2013

Date of last participant enrolment

Anticipated

Actual

18/08/2014

Date of last data collection

Anticipated

Actual

Sample size

Target

100

Accrual to date

Final

100

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Austin Health - Austin Hospital - Heidelberg

Recruitment postcode(s) [1]

3084 - Heidelberg

Funding & Sponsors

Funding source category [1]

Self funded/Unfunded

Name [1]

N/A

Address [1]

N/A

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Other collaborator category [1]

University

Name [1]

Griffith University

Address [1]

Centre for Health Practice Innovation
Room 0.01E
Health Science Building (N48)
Griffith University
170 Kessels Rd
NATHAN QLD 4111

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Human Research Ethics Committee (Austin Health)

Ethics committee address [1]

145 Studley Rd
PO Box 5555
Heidelberg
Melbourne
Victoria
3084

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

10/10/2012

Approval date [1]

01/11/2012

Ethics approval number [1]

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

A/Prof Nigel Fealy

Address

C/- of Intensive care unit
Level 2, Austin Tower
Austin Health
145 Studley Rd
Heidelberg
Melbourne
Victoria
3084

Country

Australia

Phone

61 3 9496 4834

Fax

[email protected]

Contact person for public queries

Name

Prof Leanne Aitken

Address

School of Nursing and Midwifery
Nathan Campus
Griffith University
Brisbane
Nursing Practice Development Unit,
Princess Alexandra Hospital,
Ipswich Road,
Woolloongabba QLD 4102

Country

Australia

Phone

+61 7 3176 7256;

Fax

+61 7 3176 7356

[email protected]

Contact person for scientific queries

Name

Prof Rinaldo Bellomo

Address

Austin Health
145 Studley Rd
Heidelberg
Melbourne
Victoria
3084

Country

Australia

Phone

61-3-9496 5992

Fax

[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

Source	Title	Year of Publication	DOI
Embase	Faster blood flow rate does not improve circuit life in continuous renal replacement therapy: A randomized controlled trial.	2017	https://dx.doi.org/10.1097/CCM.0000000000002568

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically