ANZCTR - Registration

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

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

ACTRN12615000100594

Ethics application status

Approved

Date submitted

13/01/2015

Date registered

4/02/2015

Date last updated

12/08/2019

Date data sharing statement initially provided

12/08/2019

Date results provided

12/08/2019

Type of registration

Prospectively registered

Titles & IDs

Public title

The Effects of Bolus and Slow Fluid Infusions in Healthy Volunteers with Shock

Scientific title

The Effects of a Bolus or Slow Intravenous Crystalloid Fluid Infusion on Oxygen Delivery in Healthy Volunteers with Compensated Shock

Secondary ID [1]

None

Universal Trial Number (UTN)

U1111-1166-0487

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Haemorrhagic Shock

Condition category

Condition code

Anaesthesiology

Anaesthetics

Cardiovascular

Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

After the venesection of 10 ml/kg Ideal Body Weight of blood over a 15 minute period from healthy fit adult subjects, participants will be randomised to receive a intravenous crystalloid fluid (Plasma-Lyte 148) for resuscitation.

The type of fluid used is Plasma-Lyte 148 solution (Baxter Healthcare).

The amount of Plasma-Lyte 148 solution that will be administered is 13 ml/kg (Ideal Body Weight) .

Plasma-Lyte 148 solution will be infused continuously via the intravenous route through a peripheral intravenous cannula.

The Plasma-Lyte 148 infusion will commence exactly 15 minutes after completion of the venesection.

Plasma-Lyte 148 solution will infused over 2 time periods/arms depending on randomisation.

1. Over a 10 minutes period (Bolus infusion group)

2. Over a 30 minutes period (Slow infusion group)

The ratio of 1:1.3 ratio of the volume of blood to the volume of Plasmalyte is adopted from the landmark clinical trial, The Saline versus Albumin Fluid Evaluation Study (SAFE).

Once the Plasma-Lyte 148 solution has been infused, data collection will be conducted for 60 minutes.

Once data collection is completed, the venesected blood will be re-infused back to the participant over a 30 minute period.

The study will then be concluded.

Participants will then be crossed over to the other infusion period/arm between 7 -14 days later i.e there will be a washout period of between 7-14 days between the 2 interventions.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

The control group will be Bolus infusion group. This group will receive the Plasma-Lyte 148 solution over a 10 minutes period (Bolus infusion group).

Control group

Dose comparison

Outcomes

Primary outcome [1]

The primary outcome is: Oxygen delivery (mls/kg/min)

This is easily measured by using non-invasive technology which continuously measure cardiac output, O2 saturation and haemoglobin levels throughout the study.

Determinants of oxygen delivery will be directly measured using state of non-invasive technology (Edwards Life Science ClearSight Device). These will include:
1. Stroke volume index (independent of heart rate)
2. Haemoglobin concentrations
3. Blood arterial saturation
4. Heart rate

Timepoint [1]

1. Baseline (before venesection)
2. Immediately post venesection
3. 30 minute post venesetion; pre-Plasmalyte infusion
4. Immediately post Plasmalyte infusion
5. 60 minutes post Plasmalyte infusion
6. Post reinfusion of the patients venesected blood

Secondary outcome [1]

Mean arterial pressure using the Edwards Lifesciences ClearSite Advanced haemodynamic monitor

Timepoint [1]

Secondary outcome [2]

Systolic blood pressure using the Edwards Lifesciences ClearSite Advanced haemodynamic monitor

Timepoint [2]

Secondary outcome [3]

Diastolic blood pressure using the Edwards Lifesciences ClearSite Advanced haemodynamic monitor

Timepoint [3]

Secondary outcome [4]

Cardiac index using the Edwards Lifesciences ClearSite Advanced haemodynamic monitor

Timepoint [4]

Secondary outcome [5]

Systemic vascular resistance using the Edwards Lifesciences ClearSite Advanced haemodynamic monitor

Timepoint [5]

Secondary outcome [6]

Stroke volume index using the Edwards Lifesciences ClearSite Advanced haemodynamic monitor

Timepoint [6]

Secondary outcome [7]

Venous blood gas including (pH,Pa02,PaCO2, base deficit) using an ABL 800 Blood Gas Monitor

Timepoint [7]

Secondary outcome [8]

Plasma haemoglobin using an ABL 800 Blood Gas Monitor

Timepoint [8]

Secondary outcome [9]

Plasma Atrial natriuetic peptide

Timepoint [9]

Baseline (before venesection of the patients blood), immediately post infusion of the Plasmalyte-148 solution, then 30 minutes and 60 minutes post infusion of the Plasmalyte-148 solution

Secondary outcome [10]

Plasma Interleukin 6

Timepoint [10]

Baseline (before venesection of the patients blood), immediately post infusion of the Plasmalyte-148 solution, then 30 minutes and 60 minutes post infusion of the Plasmalyte-148 solution

Secondary outcome [11]

Plasma Tumour necrosis factor (Alpha)

Timepoint [11]

Baseline (before venesection of the patients blood), immediately post infusion of the Plasmalyte-148 solution, then 30 minutes and 60 minutes post infusion of the Plasmalyte-148 solution

Secondary outcome [12]

Indocyanine green, which will be measured with PULSION non-invasive LiMON–Technology

Timepoint [12]

Baseline (before venesection of the patients blood), immediately post infusion of the Plasmalyte-148 solution, then 30 minutes and 60 minutes post infusion of the Plasmalyte-148 solution

Secondary outcome [13]

Vascular reactivity index using a VENDYs non invasive vascular reactivity machine.

Timepoint [13]

Baseline (before venesection of the patients blood), then 60 minutes post infusion of the Plasmalyte-148 solution

Secondary outcome [14]

Plasma lactate using an ABL 800 Blood Gas Monitor

Timepoint [14]

Baseline (before venesection of the patients blood), immediately post infusion of the Plasmalyte-148 solution, then 30 minutes and 60 minutes post infusion of the Plasmalyte-148 solution

Secondary outcome [15]

Heart Rate using the Edwards Lifesciences ClearSite Advanced haemodynamic monitor

Timepoint [15]

Eligibility

Key inclusion criteria

1. Healthy adults
2. No regular medication other than contraceptive pill
3. Normal Haemoglobin level

Minimum age

18 Years

Maximum age

45 Years

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key exclusion criteria

1. <18 years or > 45 years in age
2. Pregnancy or have given birth within 1 year
3. Hereditary haematological conditions (sickle cell anaemia and thalassemia) that are susceptible to anaemia
4. Recent (within 10 days) history of cold, fever, or upper or lower respiratory tract infection (this may theoretically increase risk of infection with venesected blood when it is being stored prior to re-infusion)
5. Morbid Obesity (BMI> 35 kg/m2)
6. Body Weight > 100 kg

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)

Allocation will be concealment will be by means of sealed opaque envelopes. The sealed envelopes will be stored in a locked facility in the department of Intensive Care at Austin Hospital, where the trial is being conducted. After informed participant consent has been obtained, an independent research assistant/investigator will open the sealed envelope which will contain one of the two randomisation groups.

1) Bolus Plasmalyte infusion group
2) Slow Plasmalyte infusion group

After a wash-period of >7days and <14 days, participants will be assigned to the alternative group.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Simple randomisation using a computer software (i.e. computerised sequence generation) will be performed by the Principle Investigator. The computer will be password protected and located in the Research Laboratory in the Department of Intensive Care at Austin Hospital. Participants will be randomly allocated to one of the two infusion groups described above.

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Crossover

Other design features

Phase

Phase 4

Type of endpoint/s

Efficacy

Statistical methods / analysis

Regarding the inference for means: the sample calculations are based on comparing two independent sample populations
1. The expected mean oxygen delivery values (mu1) in the slow volume resuscitation group = 500 ml/min/m2
2. The expected mean oxygen delivery values (mu2) in the bolus volume resuscitation group = 400 ml/min/m2
Using a 2-sided test
3. Sigma value (common standard deviation) of the samples population = 75 ml/min/m2
4. Type 1 error rate = 0.05
5. Desired power = 0.80
Result: A sample size of 9 patients is required

Statistical analysis will be performed using computerized software (SPSS for Windows version 12.0, and Graphed). For data that is non-normally distributed a Mann–Whitney test will be used and normally distributed data will be compared using the Student T test. Ordinal and nominal data will be compared using Chi square analysis. A p-value <0.05 will be considered significant.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

14/02/2015

Actual

16/02/2015

Date of last participant enrolment

Anticipated

30/06/2015

Actual

22/06/2015

Date of last data collection

Anticipated

Actual

23/06/2015

Sample size

Target

Accrual to date

Final

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]

Hospital

Name [1]

Austin Hospital

Address [1]

Studley Road, Heidelberg, 3084, Victoria, Australia

Country [1]

Australia

Funding source category [2]

University

Name [2]

Department of Surgery, and Anaesthesia Perioperative Pain Medicine Unit, University of Melbourne

Address [2]

University of Melbourne, Parkville, Victoria, 3010, Australia

Country [2]

Australia

Primary sponsor type

Hospital

Name

Department of Anaesthesia, Austin Hospital

Address

Study Road, Heidelberg, 3084, Victoria

Country

Australia

Secondary sponsor category [1]

University

Name [1]

Department of Surgery, and Anaesthesia Perioperative Pain Medicine Unit, University of Melbourne

Address [1]

University of Melbourne, Parkville, Victoria, 3084

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Human Research Ethics Unit

Ethics committee address [1]

Human Research Ethics Committee 
Austin Hospital, Studley Road, Heidelberg, 3084, Victoria

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

09/01/2015

Ethics approval number [1]

HREC/14/Austin/458

Summary

Brief summary

Numerous animal studies have shown that bolus or fast fluid infusion increases blood loss and mortality compared to a slow fluid infusion. Consistently, a high quality human randomised controlled trial also demonstrated that rapid crystalloid infusion increased mortality and complications in children with severe infections compared to those who received no bolus infusion.  To date, no human studies have explored the effects of bolus fluid infusions and the duration of these effects on haemodynamic changes, biochemical, immunological and hormonal responses compared to those effects induced by slow infusions. 

This study is the first human randomised controlled trial to investigate the effects of bolus (fast) and slow infusion of crystalloid (clear) fluids in healthy volunteers.  Participants will be randomly assigned to either a bolus (fast) infusion or a slow infusion group.  The controlled venesection (removal) of 10 ml/kg Ideal Body Weight of blood will be conducted over a 15 minute period.  Following that and after 30 minutes, participants will be resuscitated with 13 ml/kg of a either a bolus (fast) infusion (10 minutes), or a slow infusion (30 minutes) with a balanced crystalloid solution. After a 60-minute measurement period, the participants’ blood will be re-infused over a further 30-minute period. After 2 weeks, the participants will be crossed over to the other arm. 

Primary end point: Oxygen delivery, which can easily be measured by using a validated non-invasive haemodynamic monitor (Edwards Life Science ClearSight Device), a device that is used routinely as standard of care at Austin Health. 

Secondary endpoints: The effects of the rate of fluid resuscitation on mean arterial pressure, systemic vascular resistance, vascular reactivity index, biochemical, immunological and hormonal responses will also be investigated in similar timeline.  

Study Hypothesis: A slow crystalloid infusion has a more beneficial effect on oxygen delivery than a bolus (fast) crystalloid infusion in healthy volunteers (age 18 to 45 years) with induced compensated shock.  

No of participants: 9

Setting: A single centre University teaching hospital.

Safety: Detailed and stringent safety guidelines will be followed in accordance with advice from the Department of Haematology at Austin Hospital, Austin Hospital Blood Bank, Victorian Red Cross, and the Department’s of Anaesthesia and ICU.
Each experiment will conducted by a senior anaesthetist, in a theatre environment, with the appropriate monitoring and safety equipment to effectively and safely conduct this study.  

Clinical significance: These results will used to generate hypotheses and establish outcome benchmarks for future controlled trials that will directly influence how patients with haemorrhagic shock are optimally resuscitated.

Trial website

Nil

Trial related presentations / publications

Nil

Public notes

Nil

Contacts

Principal investigator

Name

A/Prof Laurence Weinberg

Address

Department of Anaesthesia, Austin Hospital, Studley Road, Heidelberg, 3084, Victoria

Country

Australia

Phone

+61 3 94965000

Fax

+61 3 94596421

Laurence.Weinberg@austin.org.au

Contact person for public queries

Name

Laurence Weinberg

Address

Department of Anaesthesia, Austin Hospital, Studley Road, Heidelberg, 3084, Victoria

Country

Australia

Phone

+61 3 94965000

Fax

+61 3 94596421

Laurence.Weinberg@austin.org.au

Contact person for scientific queries

Name

Laurence Weinberg

Address

Department of Anaesthesia, Austin Hospital, Studley Road, Heidelberg, 3084, Victoria

Country

Australia

Phone

+61 3 94965000

Fax

+61 3 94596421

Laurence.Weinberg@austin.org.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

Participants have not consented for sharing of data

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	Comparative evaluation of crystalloid resuscitation rate in a human model of compensated haemorrhagic shock.	2016	https://dx.doi.org/10.1097/SHK.0000000000000610

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

Trial Review

Registering a new trial?

Documents added manually

Documents added automatically