ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12616001570471

Ethics application status

Approved

Date submitted

9/11/2016

Date registered

14/11/2016

Date last updated

4/08/2023

Date data sharing statement initially provided

5/11/2018

Date results provided

22/10/2021

Type of registration

Prospectively registered

Titles & IDs

Public title

FentAnyl or placebo with Ketamine and rocuronium for rapid sequence inTubation in the emergency department, a multicentre randomised controlled trial: the FAKT study

Scientific title

A randomised, double blind, placebo controlled trial evaluating the impact of fentanyl as an adjunct to ketamine and rocuronium on post-induction haemodynamics & 30 day mortality of patients undergoing rapid sequence of intubation in the emergency department.

Secondary ID [1]

NIL KNOWN

Universal Trial Number (UTN)

U1111-1189-6521

Trial acronym

FAKT

Linked study record

Health condition

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

Rapid sequence intubation

Condition category

Condition code

Anaesthesiology

Anaesthetics

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Patients requiring rapid sequence intubation in the emergency department using ketamine and rocuronium in the opinion of their treating doctor will be randomised to one of two arms in a 1:1 ratio. In addition to the trial medication (described below), each patient will receive either ketamine 1mg/kg + rocuronium 1.5mg/kg (reduced dosing group), or ketamine 2mg/kg + rocuronium 1.5mg/kg (standard dose). The medications will be administered as an intravenous bolus. As the requirement for reduced dosing is multifactorial, and is not readily distilled into an algorithm, the decision as to whether to use standard or reduced dosing will be at the discretion of the treating doctor (who will be at least a senior registrar) using clinical gestalt.

The treatment arm will receive the medication detailed above, preceded by fentanyl 2mcg/kg (standard dose) or 1mcg/kg (reduced dose) as an intravenous bolus.

The drugs will be administered in the order of fentanyl (or placebo), followed by ketamine, followed by rocuronium, in a rapid sequence. Following the administration of the medications, intubation will proceed in a standardised fashion.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

The control group will be administered an equal volume of 0.9% saline rather than fentanyl. The 0.9% saline will be provided in a pre-drawn syringe, identical to those that the fentanyl is provided in.

Control group

Placebo

Outcomes

Primary outcome [1]

The percentage of patients with a systolic blood pressure falling outside of the range of 100-150mmHg.

Timepoint [1]

Within the first ten minutes following the administration of the trial medication.

Secondary outcome [1]

Secondary end-points of hypoxia (Sp02 less than or equal to 93%), as measured by continuous pulse oximetry.

Timepoint [1]

Within 10 minutes of administration of the study medication

Secondary outcome [2]

Tachycardia (HR greater than or equal to 120), as measured using continuous three lead cardiac monitoring.

Timepoint [2]

Within 10 minutes of the administration of study medication

Secondary outcome [3]

Cardiac arrest (loss of palpable pulse and ETC02<10, associated with the use of cardiac compressions or commencement of procedures to reverse traumatic cardiac arrest).

Timepoint [3]

Within 10 minutes of the administration of study medication

Secondary outcome [4]

Cormack-Lehane laryngoscopic view.

Timepoint [4]

Between the administration of study medication, and the placement of a cuffed tube in the trachea.

Secondary outcome [5]

Percentage of patients intubated on the first pass (i.e. following a single laryngoscope insertion by a single operator).

Timepoint [5]

Between the administration of study medication and the placement of a cuffed tube in the trachea.

Secondary outcome [6]

Percentage of patients in whom the use of a supraglottic airway devices is necessary.

Timepoint [6]

Within thirty minutes following the administration of study medication.

Secondary outcome [7]

Percentage of patients undergoing cricothyroidotomy.

Timepoint [7]

Within thirty minutes of the administration of study medication.

Secondary outcome [8]

All cause mortality

Timepoint [8]

30 days after enrollment

Secondary outcome [9]

Number of ventilator-free days

Timepoint [9]

Thirty days

Eligibility

Key inclusion criteria

Any patient over the age of 18 who:

1) Requires rapid sequence intubation, and;
2) In whom the proposed induction regime is at least as suitable as any of the alternatives in the opinion of the treating doctor.

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Age <18 years, known or suspected allergy to ketamine, fentanyl or rocuronium, requirement for paralysis only induction, or an alternative induction regime required in the opinion of the treating physician.

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 concealed by the use of medication (either fentanyl 200mcg/20ml or 20ml 0.9% saline) in identical syringes, supplied according to a randomisation scheduled provided to the pharmaceutical compounding company. Syringes will be labelled with an individual study number, but will otherwise be identical.

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

Block randomisation, in blocks of four, from a randomisation schedule generated from randomisation.com

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Phase 3

Type of endpoint/s

Safety

Statistical methods / analysis

A prior study by Lyon et al*, comparing etomidate and suxamethonium with fentanyl, ketamine and rocuronium (in a 'before and after' fashion), showed that approximately 80% of the first group and 40% of the second became hypotensive or hypertensive following RSI. Jabre et al’s** RCT, comparing ketamine and etomidate use for RSI showed that both were associated with similar changes in systolic blood pressure. Consequently, it seems plausible that the addition of fentanyl to an induction regime of ketamine and rocuronium could reduce the proportion of patients meeting the primary end-point from approximately 80% to approximately 40%.

As it is typical for observational studies to overstate treatment effects, a margin for error has been allowed, and the figures of 70% and 50% have been used. Using these estimates, with a power of 90%, and a significance level set at 0.05, we calculate that a sample size of 134 in each group will be necessary to detect a true difference.

To allow for dropouts, approximately 10% will be added to the planned sample size, meaning that a target of 300 patients (150 in each arm) will be recruited.

Data will be entered into an electronic spread sheet for analysis using Stata version 11 (Statacorp, TX). Normally distributed data will be described as means, with 95% confidence intervals, and non-normally distributed data will be described as medians, with interquartile range.

*Lyon RM et al. Significant modification of traditional rapid sequence induction improves safety and effectiveness of pre-hospital trauma anaesthesia. Crit Care. 2015; 19(1): 134.
**Jabre P et al. Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial. Lancet 2009; 374:293-300.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

20/08/2018

Actual

25/08/2018

Date of last participant enrolment

Anticipated

1/11/2020

Actual

3/12/2020

Date of last data collection

Anticipated

1/12/2020

Actual

5/01/2021

Sample size

Target

300

Accrual to date

Final

302

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment hospital [1]

Liverpool Hospital - Liverpool

Recruitment hospital [2]

Campbelltown Hospital - Campbelltown

Recruitment hospital [3]

Royal North Shore Hospital - St Leonards

Recruitment hospital [4]

Orange Health Service - Orange

Recruitment hospital [5]

The Northern Beaches Hospital - Frenchs Forest

Recruitment postcode(s) [1]

2170 - Liverpool

Recruitment postcode(s) [2]

2560 - Campbelltown

Recruitment postcode(s) [3]

2065 - St Leonards

Recruitment postcode(s) [4]

2800 - Orange

Recruitment postcode(s) [5]

2086 - Frenchs Forest

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Liverpool Hospital

Address [1]

Locked Bag 7103
Liverpool BC
NSW 1871

Country [1]

Australia

Primary sponsor type

Individual

Name

Ian Ferguson

Address

Liverpool Hospital
Locked Bag 7103
Liverpool BC
NSW 1871

Country

Australia

Secondary sponsor category [1]

None

Name [1]

None

Address [1]

None

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

South West Sydney Human Research Ethics Committee

Ethics committee address [1]

Liverpool Hospital HREC
Locked Bag 7103
Liverpool BC
NSW 1871

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

26/10/2017

Approval date [1]

08/12/2017

Ethics approval number [1]

Summary

Brief summary

Ketamine is an induction agent to induce general anaesthesia in the emergency department, associated with less frequent episodes of hypotension than other agents such as thiopentone1 or propofol2. However, it is typically associated with increases in blood pressure in stable patients, and can cause hypotension in shocked patients3.

In critically ill patients, avoiding hypotension is important, as it’s occurrence is known to be associated with poor outcomes4, particularly in the head injured patient5.  However, hypertension is also associated with poorer outcomes, particularly in patients with intracranial bleeds (although cause and effect is not established) 6, and is usually avoided in haemorrhagic shock, due to consensus concern about increasing bleeding7,8.

Co-administration of fentanyl during rapid sequence induction has been advocated as leading to less deviation from baseline haemodynamics9.  

It remains unclear whether in the emergency department and pre-hospital setting, this has any significant impact on mortality, and this exploratory study aims to evaluate whether patients undergoing RSI with ketamine and fentanyl, rather then ketamine and placebo have fewer episodes of adverse haemodynamic effects (systolic blood pressure less to 91 mmHg or greater than 149 mmHg) within the first 10 minutes following induction, and whether there is a subsequent difference in mortality at 3, 7 and 30 days.

The study will be powered to detect a difference in the percentage of patients who meet the primary endpoint of low or high blood pressure, and will be used to inform future work regarding difference in mortality benefit.

1.	White PF. Comparative evaluation of intravenous agents for rapid sequence induction –thiopental, ketamine and midazolam. Anaethesiology, Oct 1982; 57(4): 279-84
2.	Hug CC Jr et al. Haemodynamic effects of propofol: Data from over 25,000 patients. Anaethesia and Analgesia, 1993; 77 (4 suppl):S21-9.
3.	Miller M et al.  The haemodynamic response following ketamine induction for pre-hospital anaesthesia in shocked and non-shocked patients.  Ann Emerg Med, 2016 April;
4.	Hefner AC et al. The frequency and significance of post-intubation hypotension during emergency airway management. J Crit Care. 2012 Aug; 27(4):417, e9-13.
5.	Manly G, et al. Hypotension, hypoxia and head injury: Frequency, duration and consequences. Archiv Surg. 2001 Oct; 136(10):1118-23.
6.	Honner SK et al. Emergency department control of blood pressure in intracerebral haemorrhage. J Emerg Med. 2011; 414(4): 355-61.
7.	Bickell WH, Wall MJ Jr, Pepe PE, Martin RR, Ginger VF, Allen MK, Mattox KL. Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries. N Engl J Med. 1994 Oct 27;331(17):1105-9.
8.	Dutton RP, Mackenzie CF, Scalea TM. Hypotensive resuscitation during active hemorrhage: impact on in-hospital mortality. J Trauma. 2002 Jun;52(6):1141-6.
9.	Lyon RM et al. Significant modification of traditional r

Trial website

Trial related presentations / publications

Public notes

Attachments [1]

/AnzctrAttachments/371815-SWD18 2150 Letter - REO - HE17 245 - Approval - Ethics-signed.pdf (Ethics approval)

Contacts

Principal investigator

Name

Dr Ian Ferguson

Address

Emergency Department
Liverpool Hospital
Locked Bag 7103
Liverpool BC
NSW 1871

Country

Australia

Phone

+61 2 8738 3950

Fax

Ian.Ferguson@health.nsw.gov.au

Contact person for public queries

Name

Ian Ferguson

Address

Emergency Department
Liverpool Hospital
Locked Bag 7103
Liverpool BC
NSW 1871

Country

Australia

Phone

+61 403859555

Fax

ianferguson@doctors.org.uk

Contact person for scientific queries

Name

Ian Ferguson

Address

Emergency Department
Liverpool Hospital
Locked Bag 7103
Liverpool BC
NSW 1871

Country

Australia

Phone

+61 2 8738 3950

Fax

ian.ferguson@health.nsw.gov.au

Data sharing statement

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

Yes

What data in particular will be shared?

All trial data, in a de-identified manner, will be made available to investigators with the relevant ethical approvals.

When will data be available (start and end dates)?

The data will be available from immediately following publication, with no specific end date.

Available to whom?

Data will be made available to researchers with an ethically approved protocol detailing it's planned use.

Available for what types of analyses?

The data would be available for repeat analysis of the initial study, and systematic review and meta-analysis, including individual patient meta-analysis.

How or where can data be obtained?

Access subject to application to the chief investigator, with a requirement to provide evidence of ethical approval for planned study.

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	FentAnyl or placebo with KeTamine for emergency department rapid sequence intubation: The FAKT study protocol.	2019	https://dx.doi.org/10.1111/aas.13309
Embase	Fentanyl versus placebo with ketamine and rocuronium for patients undergoing rapid sequence intubation in the emergency department: The FAKT study-A randomized clinical trial.	2022	https://dx.doi.org/10.1111/acem.14446

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

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