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Trial registered on ANZCTR


Registration number
ACTRN12615000522516
Ethics application status
Approved
Date submitted
8/05/2015
Date registered
26/05/2015
Date last updated
26/05/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
A study comparing resuscitation outcomes following administration of an intravenous oxygen carrier (HBOC-201) to Normal Saline in urban adult trauma patients.
Scientific title
A prospective, randomised study of seriously injured, shocked adult trauma patients in an urban setting, comparing resuscitation outcomes following administration of an intravenous hemoglobin-based oxygen carrier-201 (HBOC 201) to Normal Saline.
Secondary ID [1] 283925 0
Nil
Universal Trial Number (UTN)
U1111-1170-0061
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Haemorrhagic shock 290928 0
Major Trauma 295069 0
Condition category
Condition code
Injuries and Accidents 291283 291283 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Initial intervention criteria: A Shock Index (i.e. Heart Rate / Systolic Blood Pressure) >= 1.0 and other eligibility criteria met

Intervention: Initial intravenous infusion (usually over ~ 20 minutes) of HBOC-201 (250 ml) or NS ( in 250 ml increments up to 1,000ml ml)

HBOC-201 is an experimental intravenous fluid with oxygen carrying capacity derived from bovine red blood cell hemoglobin. The HBOC-201 is a deep red coloured fluid.

Maximum total dose: Doses of IV fluid following initial infusion will be HBOC-201 (250 ml) or NS solution to maintain BP > 70 mmHg depending on randomisation arm. If further IV fluid is indicated in the HBOC-201 arm after a maximum limit of 2 units of HBOC-201 [2 doses of 250 ml] has been infused standard care (NS) will be administered. If the Systolic BP is < 70mmHg whilst the HBOC-201 is being infused either as the initial or the second dose of 250 ml, NS will also be administered via a second IV line until the BP is > 70mmHg.

IV infusion stopping criterion: A Systolic Blood Pressure > 120 mmHg and Pulse Rate < 120 beats/minute.
Intervention code [1] 288614 0
Treatment: Drugs
Comparator / control treatment
Current ‘standard of care’ administration of Normal Saline
Control group
Active

Outcomes
Primary outcome [1] 291282 0
Mortality as assessed by hospital records
Timepoint [1] 291282 0
Upto 28days after date of injury or at discharge
Secondary outcome [1] 306418 0
Serious adverse events, defined as abnormalities in
1. Haemoglobin levels on days 1-4, 7, 14 and 28
2. Acute renal injury as defined by the RIFLE criteria through urine output and creatinine
3. Acute myocardial infarction (defined as normal Troponin I on admission with subsequent Troponin I rise and diagnostic ECG changes)
4. Ischaemic stroke
5. Anaphylaxis
6. Blood and blood product administration
7. Cardiac arrest
8. Length of Stay in ICU and hospital ward.

Assessed and notified by researchers involved in the care of the patient, research personnel involved with completion of case reports through contact at the decided intervals, and retrospectively through hospital records in cases of missing data.
Timepoint [1] 306418 0
Upto 28days after date of injury or at discharge

Eligibility
Key inclusion criteria
1) Age 18 to less than 55 years
2) Injury with obvious/suspected haemorrhagic shock
3) Pre-hospital Shock Index >=1.0
4) Road transport by MICA paramedic to either The Alfred or the Royal Melbourne Hospitals
5) External haemorrhage control attempted in patients with external bleeding
6) IV access secured
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Penetrating Traumatic Brain Injury
2) Paralysis (not as a result of paralysing agent administration).
3) Pregnancy—known or suspected by next of kin if at scene
4) Cardiac arrest (an absence of spontaneous circulation)
5) Known allergy to HBOC-201
6) Known opposition to HBOC-201 administration
7) Burn > 20% body surface area (BSA) (partial or full thickness)
8) Blood for transfusion available at scene

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)
48 Ambulance Victoria road cars (MICA Single Responder and MICA Stretcher vehicles) will be equipped with 2 units of 250 ml HBOC-201.
500 opaque sealed envelopes with equal allocation of NS or HBOC-201 will be prepared. The envelope will be opened by the attending Mobile Intensive Care Officer if the patient meets the enrolment criteria.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Sealed, opaque allocation envelopes will be block randomised and distributed across the 48 road cars in batches of 4. Each batch will contained 50% NS arm allocations and 50% HBOC201 arm allocations.

If the patient is identified as meeting the eligibility criteria, the attending paramedic will open an envelope containing a card indicating randomisation to ‘standard therapy’ Normal Saline or randomisation to HBOC-201.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Nil
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Efficacy statistical significance level will be p < 0.05 at final analysis. Contingency Tables will be developed for dichotomised ordinal data. Fisher’s exact test will be used to calculate the significance of differences. Continuous data will be analysed using Student’s t-test with log transformations conducted as required for normalisation. Holm t-test adjustments will be conducted to adjust for the wide range of secondary outcome measures. Kaplan-Meier survival analysis will be undertaken to generate tables and plots of the survival or hazard function post randomisation. Chi Square or Fisher’s exact tests will compare Rate Ratios along with Wilcoxon rank sum for duration.

The effect size of this improvement is currently unknown. This pilot study will determine an estimate of the effect of prehospital HBOC-201 in shocked trauma patients. Trauma Registry estimates are that 75% of eligible patients with a prehospital Shock Index of > 1.0 have a Shock index > 1.0 on Trauma Centre arrival. Assuming a minimum acceptable effect which reduces the number of patients arriving at the Trauma Centre(s) with a Shock Index > 1.0 by an absolute 30.0% (proportion = 0.45) with an alpha of 0.050 and a power of 0.80, the number of total patients needed to enrol in this pilot study is 96 (48 in each arm) (Stata 1C/13.1). 110 will be recruited in total to allow for loss to follow-up.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/08/2015
Actual
Date of last participant enrolment
Anticipated
1/07/2016
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
110
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 1975 0
The Alfred - Prahran
Recruitment hospital [2] 1976 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment postcode(s) [1] 7703 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 288566 0
Hospital
Name [1] 288566 0
Alfred Health
Country [1] 288566 0
Australia
Funding source category [2] 288567 0
Other
Name [2] 288567 0
HbO2 Therapeutics LLC
Country [2] 288567 0
United States of America
Primary sponsor type
Hospital
Name
Alfred Health
Address
55 Commercial Road
Melbourne
Victoria
3004
Country
Australia
Secondary sponsor category [1] 287279 0
Other
Name [1] 287279 0
National Trauma Research Institute
Address [1] 287279 0
85-89 Commercial Road
Melbourne
VIC 3004
Country [1] 287279 0
Australia
Other collaborator category [1] 277760 0
Hospital
Name [1] 277760 0
Melbourne Health
Address [1] 277760 0
Royal Parade
Parkville
Victoria
3053
Country [1] 277760 0
Australia
Other collaborator category [2] 277761 0
Other
Name [2] 277761 0
Ambulance Victoria
Address [2] 277761 0
375 Manningham Road
Doncaster
Victoria
3018
Country [2] 277761 0
Australia
Other collaborator category [3] 277762 0
University
Name [3] 277762 0
Monash University
Address [3] 277762 0
Department of Community Emergency Health and
Paramedic Practice (DCEHPP),
Building H
McMahons Road
Frankston Vic, 3199
Australia
Country [3] 277762 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290428 0
The Alfred Hospital Ethics Committee
Ethics committee address [1] 290428 0
55 Commercial Road
Melbourne
Victoria
3004
Ethics committee country [1] 290428 0
Australia
Date submitted for ethics approval [1] 290428 0
Approval date [1] 290428 0
05/04/2013
Ethics approval number [1] 290428 0
141/12

Summary
Brief summary
A prospective, randomised study of seriously injured, shocked adult trauma patients in an urban setting, comparing resuscitation outcomes and serious adverse effects of an intravenous oxygen carrier (HBOC-201) to Normal Saline. In this Victorian study environment it is expected that all patients transported by road to a Major Trauma Centre will have prehospital times of >=20 minutes from the time of first ambulance arrival.
Trial website
hboc-201victoria.com
Trial related presentations / publications
Nil
Public notes
Nil

Contacts
Principal investigator
Name 45646 0
Prof Mark Fitzgerald
Address 45646 0
Director of Trauma Services
The Alfred
55 Commercial Road
Commercial Road
Melbourne
VIC 3004

Director National Trauma Research Institute
85-89 Commercial Road
Melbourne
VIC 3004
Country 45646 0
Australia
Phone 45646 0
+61 3 9076 2000
Fax 45646 0
+61390765319
Email 45646 0
[email protected]
Contact person for public queries
Name 45647 0
Alexander Olaussen
Address 45647 0
55 Commercial Road
Melbourne
Victoria
3004
Country 45647 0
Australia
Phone 45647 0
+61 3 9076 2000
Fax 45647 0
Email 45647 0
[email protected]
Contact person for scientific queries
Name 45648 0
Mark Fitzgerald
Address 45648 0
55 Commercial Road
Melbourne
Victoria
3004
Country 45648 0
Australia
Phone 45648 0
+61390762000
Fax 45648 0
+61390765319
Email 45648 0
[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

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