ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12615001180505

Ethics application status

Approved

Date submitted

19/10/2015

Date registered

3/11/2015

Date last updated

26/04/2022

Date data sharing statement initially provided

17/04/2019

Date results information initially provided

17/04/2019

Type of registration

Prospectively registered

Titles & IDs

Public title

Continuous Positive Airway Pressure (CPAP) for the treatment of severe respiratory distress in the pre-hospital setting

Scientific title

Continuous Positive Airway Pressure (CPAP) trial for the treatment of severe respiratory distress by ambulance paramedics in the pre-hospital setting.

Secondary ID [1]

Nil

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

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

Severe respiratory distress.

Heart failure

Condition category

Condition code

Respiratory

Other respiratory disorders / diseases

Cardiovascular

Other cardiovascular diseases

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Continuous Positive Airway Pressure (CPAP) and usual care.
CPAP will be delivered continuously by a CPAP facial mask, set at 10cm H2o by ambulance paramedics.
CPAP will be delivered by the paramedic from identification of severe respiratory distress until arrival at the hospital.
Usual care is the care routinely administered by paramedics for severe respiratory distress that is guided by the ambulance Clinical Practice Guidelines.

Intervention code [1]

Treatment: Devices

Comparator / control treatment

Usual care is the care routinely administered by paramedics for severe respiratory distress that is guided by the ambulance Clinical Practice Guidelines. This consists of oxygen delivered by mask or bag ventilation, vasodilators if the patient is in acute pulmonary oedema, and bronchodilators if the patient has a wheeze.

Control group

Active

Outcomes

Primary outcome [1]

Changes in respiratory rate assessed by paramedics, as indicated on electronic patient care record (e-PCR)

Timepoint [1]

Paramedic arrival within 5 minutes at the prehospital scene to immediately prior to arrival to the emergency department

Primary outcome [2]

Changes in the VAS dyspnoea score measured by a Visual Analogue Scale that patients rate their difficulty in breathing from 1 (no shortness of breath) to 10 (worst difficulty in breathing imaginable)

Timepoint [2]

Paramedic arrival within 5 minutes at the prehospital scene to immediately prior to arrival to the emergency department

Primary outcome [3]

Duration of hospital length of stay (LOS) (days) - as determined by hospital records

Timepoint [3]

Length of stay will be calculated in days. after discharge from hospital

Secondary outcome [1]

Changes in peripheral oxygen saturation (SpO2) using pulse oximetry and recorded on electronic patient care record by paramedics that is uploaded to ambulance server

Timepoint [1]

From paramedic arrival within 5 minutes at the prehospital scene to immediately prior to arrival to the emergency department.

Secondary outcome [2]

Time from paramedics arrival on scene to arrival at the hospital (in minutes) - data obtained from ambulance Computer Aided Dispatch data that is uploaded to ambulance server

Timepoint [2]

Minutes from time of arrival at scene to time of hospital arrival from Computer Aided Dispatch data that is uploaded to ambulance server

Secondary outcome [3]

Occurrence of intubations.
Pre-hospital data will be collected from the Ambulance Service electronic patient care record, in-hospital data will be collected from the medical record.

Timepoint [3]

ED discharge; data from emergency department informations system linked to ambulance services database

Secondary outcome [4]

Proportion of ICU admissions.
ICU admission and discharge time and date will be collected from the hospital medical record.

Timepoint [4]

Hospital discharge

Secondary outcome [5]

Duration of hospital LOS (days); data from medical record review linked to ambulance services database

Timepoint [5]

Hospital discharge

Secondary outcome [6]

Survival to hospital discharge.
Survival outcome will be obtained from the hospital medical record.

Timepoint [6]

Hospital discharge

Secondary outcome [7]

Duration of CPAP and oxygen therapy recorded by paramedics on electronic patient care record that is uploaded to ambulance server

Timepoint [7]

ED discharge

Secondary outcome [8]

Duration of ED continuation of CPAP for at least 30 minutes assessed by review of hospital records;

Timepoint [8]

Hospital discharge

Secondary outcome [9]

Proportion of clinical complications, e.g. unplanned intubation, cardiac arrest; adverse events, e.g. barotrauma all assessed from review of hospital records;

Timepoint [9]

Continuous monitoring from start of CPAP to one hour post end of CPAP

Secondary outcome [10]

30-day survival

Timepoint [10]

30 days after initial event

Eligibility

Key inclusion criteria

Age 40 plus years, transported to a metropolitan hospital by ambulance, respiratory rate > 22 breaths per minute and identified by paramedics as experiencing severe respiratory distress of non-traumatic origin which is deteriorating despite 5 minutes of appropriate therapy

Minimum age

40 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Excluded if immediate endotracheal intubation or other methods of airway control, e.g. laryngeal mask airway are required; unconscious or only responds to pain; systolic blood pressure <90mmHg; uncooperative patient; possible pneumothorax, anaphylaxis, drowning, smoke inhalation, or aspiration

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)

Group allocation will be placed in externally numbered, sealed opaque tamper-evident envelopes. Research paramedics will be provided with a set of randomisation envelopes. As each is used, it will be replaced at the earliest convenient time from the remaining envelopes held at the ambulance station

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

Computer generated randomisation will be used to create a randomisation schedule. Block randomisation will be used, with a random block size, to ensure relative balance of the numbers in each group at any time

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Parallel

Other design features

Phase

Phase 3

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

Statistical analysis
All analyses will be performed on an intention-to-treat basis. For missing data, the number of available observations will be reported. No assumptions will be made about the missing data. Baseline cohort characteristics such as age, sex, presenting problem will be compared between treatment groups using chi-square tests for categorical variables and independent sample t-tests (or the non-parametric equivalents) for continuous variables. The tests will be two-sided and considered statistically significant if p<0.01. The primary outcomes and secondary outcomes that are continuous variables will firstly be compared between study groups using either parametric (ttest) or non-parametric (Mann-Whitney) statistics, depending on the underlying assumptions of the test being met.

Regression techniques will be used to model the effect of the treatment group (CPAP and usual care compared to usual care), with adjustment for potential confounders. Previous studies have not shown delay at the scene as a result of administering CPAP. Patients will usually be in the ambulance when CPAP is commenced. Nevertheless we will collect these data and adjust for pre-hospital time intervals in multivariable analyses if required. An ‘a priori’ subgroup analysis of patients with APO, COPD and pneumonia will also be conducted. All statistical analyses will be undertaken under the direction of the nominated biostatistician and will include the use of SPSS, and STATA statistical software.

Sample size and power
Calculations are based on 90% power and an alpha level of 0.05 (PS Power and Sample Size
Calculations, V 3.0, Jan 2009):
Respiratory rate: The mean decrease in respiratory rate under standard care of 4.1 breaths per
minute (13%) (SD 5.8 breaths per minute) was determined from 1729 SJA-WA cases transported
between 20.09.2012 and 19.09.2013 with APO (15% of cases), COPD (36%) or respiratory tract
infections (49%). Assuming the SD of 10.4 observed in the pilot study, if there is an additional 20%
difference in the respiratory rate in the experimental group, we need to study 60 patients in each
group to be able to reject the null hypothesis that the population means of the experimental and
control groups are equal.
Dyspnoea score: Based on prehospital data, the decrease in dyspnoea under standard care is
approximately 1 unit (SD 3.1). Assuming the same SD, and an additional 2 unit difference in the
experimental group, we need to study 25 patients in each group to be able to reject the null
hypothesis that the population means of the experimental and control groups are equal.
To ensure sufficient power to enable sub-group multivariable analyses and assuming a minimum
prevalence of 16% (1/6) in each subgroup: (1) patients with respiratory rates >=25; (2)
APO; (3) COPD; (4) respiratory tract infections; we plan to recruit 360 patients per group (for 1/6
prevalence we require 6 x 60 patients per group), i.e. 720 in total.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

23/11/2015

Actual

3/03/2016

Date of last participant enrolment

Anticipated

26/11/2017

Actual

31/12/2018

Date of last data collection

Anticipated

31/05/2019

Actual

30/06/2019

Sample size

Target

720

Accrual to date

Final

708

Recruitment in Australia

Recruitment state(s)

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

WA Department of Health SHRAC Research Translation Project funding (R10)

Address [1]

Research Development Unit
Department of Health WA
PO Box 8172
Perth Business Centre
Perth WA 6849

Country [1]

Australia

Primary sponsor type

University

Name

Curtin University

Address

Kent Street Bentley Western Australia 6102

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Nil

Address [1]

Nil

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Curtin University Human Research Ethics Committee

Ethics committee address [1]

Curtin University
Kent Street
Bentley WA 6102

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

26/08/2015

Approval date [1]

03/12/2015

Ethics approval number [1]

HR220/2015

Ethics committee name [2]

Sir Charles Gairdner and Osborne Park Health Care Group (SCGOPHCG) Human Research Ethics Committee (HREC)

Ethics committee address [2]

Level 2 A Block, Hospital Ave, Nedlands, WA 6009

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

Approval date [2]

16/03/2017

Ethics approval number [2]

2016-148

Summary

Brief summary

This randomised controlled trial (RCT) aims to compare clinical outcomes for patients with severe respiratory distress who receive continuous positive airway pressure (CPAP) in addition to usual care to those who only receive usual care in the pre-hospital setting.

CPAP is a central part of treatment for patients with severe respiratory distress in the emergency department (ED) and in hospital. The evidence for the use of CPAP in the pre-hospital setting is weak and studies have measured outcomes such as in-hospital mortality that can be attributed to in-hospital care. Furthermore, there is a paucity of robust studies from pre-hospital settings that do not rely on physician or critical care specialist managed care. Robust studies are essential to demonstrate the benefit of CPAP in the pre-hospital setting before the widespread introduction of the therapy into Australian prehospital clinical practice.

The study will be conducted in the Perth metropolitan area. St John Ambulance (SJA-WA) provides all road-based emergency ambulance services in WA. All emergency calls for an ambulance in WA are received by SJA-WA service operations centre located in Perth. Ambulances are staffed by paramedics with advanced life support skills.

This study will use dyspnoea scores as a primary outcome. Dyspnoea (respiratory distress) is a highly distressing symptom: patients describe a sensation of air hunger or suffocation. Alleviating suffering from severe breathlessness is a top priority in the care of patients with severe respiratory distress. The American Thoracic Society stress dyspnoea can and should be measured. Dyspnoea scales have been shown to predict hospital admissions, in-hospital mortality and early readmission in acute exacerbations of COPD. As such, dyspnoea scales are an appropriate primary outcome measure for pre-hospital research in patients with respiratory distress. Any pre-hospital study that demonstrates a reduction in patient distress is likely to change ambulance practice in the same way that interventions that reduce pain would be implemented.

In summary, severe respiratory distress is a medical emergency. CPAP improves outcomes in patients with severe respiratory distress in the ED and in-hospital setting but there is a paucity of information on the efficacy of CPAP initiated early in the Australian pre-hospital setting. It is incorrect to assume that interventions applied in-hospital have similar efficacy pre-hospital, due to the differences in capacity and capabilities between the two settings. Therapies shown to be efficacious in hospitals need to be evaluated in the pre-hospital setting to ensure their safety and effectiveness prior to introduction. This information is critical to establishing the evidence base underpinning this therapy prior to ambulance services incorporating CPAP as routine clinical practice.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Judith Finn

Address

Prehospital Resuscitation and Emergency Care Research Unit, School of Nursing, Midwifery and Paramedicine, Curtin University, GPO Box U1987, Perth, Western Australia 6845

Country

Australia

Phone

+61 8 9266 4447

Fax

[email protected]

Contact person for public queries

Name

Prof Judith Finn

Address

Prehospital Resuscitation and Emergency Care Research Unit, School of Nursing, Midwifery and Paramedicine, Curtin University, GPO Box U1987, Perth Western Australia 6845

Country

Australia

Phone

+61 8 9266 4447

Fax

[email protected]

Contact person for scientific queries

Name

Prof Judith Finn

Address

Prehospital Resuscitation and Emergency Care Research Unit, School of Nursing, Midwifery and Paramedicine, Curtin University, GPO Box U1987, Perth Western Australia 6845

Country

Australia

Phone

+61 8 9266 4447

Fax

[email protected]

Data sharing statement

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

No/undecided IPD sharing reason/comment

Confidential patient care records

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
4228	Ethical approval			[email protected]
4229	Study protocol			[email protected]

Results publications and other study-related documents

Documents added manually

Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
Study results article	Yes		Finn JC, Brink D, McKenzie N, Garcia A, Tohira H, ... [More Details]	369501-(Uploaded-25-04-2022-16-44-17)-Journal results publication.pdf

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Prehospital continuous positive airway pressure (CPAP) for acute respiratory distress: A randomised controlled trial.	2022	https://dx.doi.org/10.1136/emermed-2020-210256

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

Trial Review

Documents added manually

Documents added automatically