Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12612001054808
Ethics application status
Approved
Date submitted
1/10/2012
Date registered
3/10/2012
Date last updated
5/09/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Feasibility study of normoxic versus hyperoxic therapy after cardiac arrest
Scientific title
A multi-centred feasibility study investigating whether a strategy of titrated oxygen administration leads to a lower mean oxygen saturation measured by pulse oximetry at hospital admission than standard care with high concentration oxygen in adults resuscitated from out-of-hospital VF and VT cardiac arrest
Secondary ID [1] 281327 0
Nil
Universal Trial Number (UTN)
U1111-1135-3116
Trial acronym
HOT OR NOT feasibility study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Out-of-hospital cardiac arrest 287546 0
Condition category
Condition code
Cardiovascular 287870 287870 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients assigned to the ‘avoidance of hyperoxia’ arm will receive titrated oxygen from the time of ROSC aiming to achieve oxygen saturation of 90-94% via pulse oximeter. If pulse oximetry cannot be established or stops working in the ambulance, patients will be administered 100% oxygen until such time as working pulse oximetry can be established to avoid any risk of severe undetected hypoxaemia. Titrated oxygen therapy via adjustments in ventilator inspired oxygen concentration will then be maintained throughout the period of treatment in the emergency department and ICU up until extubation or 72 hours post ROSC (whichever is sooner). Once patients have arrived in the hospital, oxygen can be titrated according to blood gases if pulse oximetry is not reading reliably. In these circumstances, the oxygen concentration should be titrated to the oxygen saturation on the blood gases rather than to the PaO2.
Intervention code [1] 285790 0
Treatment: Devices
Comparator / control treatment
Patients assigned to the ‘standard care’ arm will receive usual care. This will involve administration of 100% oxygen by the ambulance officers. Subsequently, the treating hospital clinician, in accordance with usual clinical practice, will determine the oxygen target.
Control group
Active

Outcomes
Primary outcome [1] 288090 0
Mean oxygen saturation measured by pulse oximetry (in the pre-hospital period)
Timepoint [1] 288090 0
Oxygen saturation will be recorded minutely in the pre-hospital post-resuscitation period (where measurements are available)
Secondary outcome [1] 299406 0
Mean oxygen saturation measured by pulse oximetry (in the emergency department)
Timepoint [1] 299406 0
First recorded oxygen saturation on hospital arrival and every 30 minutes thereafter while in the emergency department.
Secondary outcome [2] 299407 0
Mean oxygen saturation measured by pulse oximetry (in the Intensive Care Unit)
Timepoint [2] 299407 0
Six hourly until 72 hours post ICU admission or extubation (whichever is first)
Secondary outcome [3] 299408 0
Mean partial pressure of oxygen in arterial whole blood based on arterial blood gas measurements (in the Intensive Care Unit)
Timepoint [3] 299408 0
Six hourly until 72 hours post ICU admission or extubation (whichever is first)
Secondary outcome [4] 299409 0
Documented desaturation below 88% on pulse oximetry in the intensive care unit (based on episodes of desaturation documented in the clinical record)
Timepoint [4] 299409 0
Any episodes documented on the ICU clinical record until 72 hours or extubation (whichever is sooner). Note that the end of an individual episode will be defined by when there is a documented saturation of more than 88% recorded
Secondary outcome [5] 299410 0
Mean partial pressure of carbon dioxide in whole arterial blood based on arterial blood gas measurements (in the Intensive Care Unit)
Timepoint [5] 299410 0
Six hourly until 72 hours post ICU admission or extubation (whichever is first)
Secondary outcome [6] 299411 0
Proportion of patients who survive with sufficiently good neurological outcome to be discharged to home or rehabilitation. (Note that we intend to use this as the primary end point for a phase III study which will follow this feasibility study. We intend to include patients enrolled in this study in the phase III study provided that significant protocol amendments are not required. The end of this study current study will be used as an interim analysis for the phase III study and will be used to make adjustments in the required sample size for the main study if required.)
Timepoint [6] 299411 0
Hospital discharge
Secondary outcome [7] 299412 0
Duration of Intensive Care Unit stay
Timepoint [7] 299412 0
Determined at Intensive Care Unit discharge
Secondary outcome [8] 299413 0
Duration of Hospital stay
Timepoint [8] 299413 0
Determined at Hospital Discharge
Secondary outcome [9] 299414 0
Quality of life measure by the EQ5D
Timepoint [9] 299414 0
6 months

Eligibility
Key inclusion criteria
1. Return of spontaneous circulation following cardiac arrest due to a primary cardiac cause with an initial rhythm of VF or VT
2. Aged 16-90 years
3. Ventilated via endotracheal tube or laryngeal mask airway.
Minimum age
16 Years
Maximum age
90 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Obvious pregnancy 2. Living in supported care or a nursing home 3. Terminal disease 4. More than 20 minutes have elapsed since return of spontaneous circulation

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)
1. When paramedics have a patient who fulfils eligibility criteria they will contact the local ICU who will check the participant's eligibility and open an opaque envelope that contains treatment allocation. The ICU staff will relay this to the paramedic. All patients enrolled will be unconscious at the time of enrolment.
OR
2. The Ambulance manager on site at the cardiac arrest will open an opaque envelope containing the patient's treatment allocation and will tell the treating paramedic
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be achieved by sequential numbered sealed envelopes, which will be prepared by a third party, who will receive a randomisation schedule generated by a statistician. There will be block randomisation stratified by ICU randomisation centre OR ambulance manager vehicle. Patients will be randomly assigned to either the ‘avoidance of hyperoxia’ or ‘standard care’ in a 1:1 ratio by the local study ICU when they fulfil eligibility criteria.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Patients will be blinded as to the treatment allocation; however, due to the nature of the intervention, blinding of investigators will not be possible.
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Date of first participant enrolment
Anticipated
6/10/2012
Actual
13/10/2012
Date of last participant enrolment
Anticipated
Actual
21/09/2013
Date of last data collection
Anticipated
Actual
Sample size
Target
42
Accrual to date
Final
Recruitment outside Australia
Country [1] 4579 0
New Zealand
State/province [1] 4579 0

Funding & Sponsors
Funding source category [1] 286089 0
Self funded/Unfunded
Name [1] 286089 0
N/A
Country [1] 286089 0
Primary sponsor type
Other Collaborative groups
Name
Medical Research Institute of New Zealand
Address
Medical Research Institute of New Zealand
Private Bag 7902
Wellington 6242
Country
New Zealand
Secondary sponsor category [1] 284903 0
Charities/Societies/Foundations
Name [1] 284903 0
Wellington Free Ambulance
Address [1] 284903 0
19 Davis Street,
Pipitea 6011
Wellington
Country [1] 284903 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288143 0
Northern A Health and Disability Ethics Committee
Ethics committee address [1] 288143 0
Ministry of Health
1 The Terrace
PO BOX 5013
Wellington
6011
Ethics committee country [1] 288143 0
New Zealand
Date submitted for ethics approval [1] 288143 0
03/08/2012
Approval date [1] 288143 0
28/08/2012
Ethics approval number [1] 288143 0
12/NTA/13

Summary
Brief summary
In animal models, exposure to high levels of oxygen after cardiac arrest worsens neurological outcome. However, clinical data are limited, and standard care of patients after cardiac arrest includes exposure to abnormally high levels of oxygen for prolonged periods. In this RCT, 42 patients resuscitated from community cardiac arrest will receive either standard therapy with high concentration oxygen or careful titration of oxygen to avoid either abnormally high or low oxygen levels. The feasibility study will be undertaken in Auckland, Wellington, and Christchurch. This study will determine whether patients can be effectively randomised into a study with the proposed design, and whether separation of oxygen exposure between study groups can be achieved. If careful titration of oxygen is ultimately shown to reduce brain injury after cardiac arrest, this finding will have a major impact on the management of cardiac arrest in New Zealand and internationally.
Trial website
Trial related presentations / publications
Young P, Bailey M, Bellomo R, Bernard S, Dicker B, Freebairn R, Henderson S,
Mackle D, McArthur C, McGuinness S, Smith T, Swain A, Weatherall M, Beasley R.
HyperOxic Therapy OR NormOxic Therapy after out-of-hospital cardiac arrest (HOT
OR NOT): a randomised controlled feasibility trial. Resuscitation. 2014
Dec;85(12):1686-91. doi: 10.1016/j.resuscitation.2014.09.011. Epub 2014 Sep 28.
Public notes

Contacts
Principal investigator
Name 34779 0
Dr Paul Young
Address 34779 0
Intensive Care Unit
Wellington Hospital
Private Bag 7902
Newtown
Wellington 6242
Country 34779 0
New Zealand
Phone 34779 0
+64274552269
Fax 34779 0
Email 34779 0
[email protected]
Contact person for public queries
Name 18026 0
Dr Paul Young
Address 18026 0
Intensive Care Unit
Wellington Regional Hospital
Private Bag 7902
Wellington 6242
Country 18026 0
New Zealand
Phone 18026 0
+6448060432
Fax 18026 0
Email 18026 0
[email protected]
Contact person for scientific queries
Name 8954 0
Dr Paul Young
Address 8954 0
Intensive Care Unit
Wellington Regional Hospital
Private Bag 7902
Wellington 6242
Country 8954 0
New Zealand
Phone 8954 0
+6448060432
Fax 8954 0
Email 8954 0
[email protected]

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No Supporting Document Provided



Results publications and other study-related documents

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