Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001764820
Ethics application status
Approved
Date submitted
27/11/2021
Date registered
23/12/2021
Date last updated
28/11/2022
Date data sharing statement initially provided
23/12/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Alfentanil versus fentanyl with ketamine for emergency department rapid sequence intubation: The A-FAKT study, a randomised clinical trial.
Scientific title
A comparison of alfentanil with fentanyl on the post-induction haemodynamics of patients undergoing rapid sequence intubation with ketamine and rocuronium in the emergency department: The A-FAKT study, a pilot randomised controlled trial.
Secondary ID [1] 305904 0
None
Universal Trial Number (UTN)
U1111-1272-0382
Trial acronym
The A-FAKT study
Linked study record
Not applicable

Health condition
Health condition(s) or problem(s) studied:
Rapid sequence intubation 324468 0
Condition category
Condition code
Emergency medicine 321959 321959 0 0
Resuscitation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm one will receive 2.5 - 15 micrograms per kilogram of alfentanil intravenously in addition to ketamine and rocuronium to facilitate rapid sequence intubation. The bolus of alfentanil will be given immediately prior to the other medications in the regimen (ketamine, followed by rocuronium) without a significant pause between.
The volume of intravenous alfentanil administered will be the equivalent that the treating doctor would administer if using open label fentanyl in a concentration of 10 micrograms per millilitre. I.e. if the treating doctor would aim to administer 100 micrograms of open label fentanyl (10 ml in the concentration used in this study), they would administer 10 ml (containing 500 mcg) of alfentanil in this arm.
The volume of medication administered will be recorded on the case report form, and also in a separate controlled drugs register, which will be checked by two independent staff members.
Intervention code [1] 322301 0
Treatment: Drugs
Comparator / control treatment
Arm two will receive 0.5-3 micrograms per kilogram of fentanyl, in addition to ketamine and rocuronium to facilitate rapid sequence intubation. The bolus of fentanyl will be given immediately prior to the other medications in the regimen (ketamine, followed by rocuronium) without a significant pause between.
The volume of intravenous fentanyl administered will be the same that the treating doctor would administer if using open label fentanyl in a concentration of 10 micrograms per millilitre. I.e. if the treating doctor would aim to administer 100 micrograms of open label fentanyl (10 ml in the concentration used in this study), they would administer 10 ml (containing 100 mcg of fentanyl) in this arm.
The volume of medication administered will be recorded on the case report form, and also in a separate controlled drugs register, which will be checked by two independent staff members.
Control group
Active

Outcomes
Primary outcome [1] 329713 0
The primary outcome will be a composite of:
• One or more episode of hypotension (systolic blood pressure <100mmHg within 6 minutes of induction, and/or;
• One or more episode of hypertension (systolic blood pressure >160mmHg within 6 minutes of induction, and/or;
• A rise in systolic blood pressure of >20% if the starting blood pressure exceeds 160mmHg.
A fall in systolic blood pressure of >20% if the starting blood pressure is below 100 mmHg.

Blood pressure will be measured using non-invasive oscillometry (an automated non-invasive blood pressure machine).
Timepoint [1] 329713 0
Within six minutes of the induction of anaesthesia (defined as the commencement of the study drug bolus).
Secondary outcome [1] 403565 0
Hypoxia (oxygen saturations of less than or equal to 93%) assessed by continuous pulse oximetry.
Timepoint [1] 403565 0
Within six minutes of the induction of anaesthesia
Secondary outcome [2] 403566 0
Hypotension (systolic blood pressure less than 100mmHg).

Blood pressure will be measured using non-invasive oscillometry (an automated non-invasive blood pressure machine).
Timepoint [2] 403566 0
Within six minutes of the induction of anaesthesia.
Secondary outcome [3] 403567 0
Hypertension (systolic blood pressure >160 mmHg)

Blood pressure will be measured using non-invasive oscillometry (an automated non-invasive blood pressure machine).
Timepoint [3] 403567 0
Within six minutes of the induction of anaesthesia.
Secondary outcome [4] 403568 0
Cormack and Lehane laryngeal view
Timepoint [4] 403568 0
On each intubation attempt (each attempt defined as following the insertion of a laryngoscope blade into the mouth by a single operator).
Secondary outcome [5] 403569 0
Proportion of participants intubated on first attempt. This data will be recorded on the case report form in real time.

An attempt at intubation is defined as an insertion of a laryngoscope blade by a single operator.
Timepoint [5] 403569 0
On first intubation attempt.
Secondary outcome [6] 403570 0
Mortality at 30-days following enrolment
Timepoint [6] 403570 0
30-days following enrolment.
Secondary outcome [7] 403571 0
Duration of mechanical ventilation in hours (censored at 30 days), which will be assessed by review of the electronic medical record by a member of the research team at least 30 days following enrolment.
Timepoint [7] 403571 0
30-days following enrolment.

Eligibility
Key inclusion criteria
Adult patients (18 years or older) undergoing rapid sequence intubation in participating emergency departments where the treating clinician intends to use an opioid in combination with ketamine and rocuronium.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Allergy to study medications.
• Hypotensive at baseline (SBP <100 mmHg) or shock index (pulse/SBP >1.0)
• No doctor trained in the study protocol available to oversee.
• Alternative induction regime required in the judgment of the treating doctor.
• Overwhelmed emergency department in the judgment of the treating doctor.
• COVID or suspected COVID infection.

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 concealment using a randomly generated sequence and opaque study envelopes.
Following screening, enrolled patients will be allocated the next envelope in the sequence, which will be provided to a doctor and nurse otherwise uninvolved in patient care.
These staff members will open the envelope remotely from the treating team, and prepare a syringe of either 200 micrograms of fentanyl, or 1 milligram of alfentanil, drawn up to 20 ml. The syringe will be labelled with an adhesive sticker marked: A-FAKT study, participant number X' and will then be provided to the treating team.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will occur in blocks of 10, generated using the online web interface '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 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The primary analysis will be an unadjusted, modified intention-to-treat comparison of the proportion of patients in each group meeting the primary outcome using a chi-squared test. Categorical outcomes will be presented as numbers and percentages, with absolute risk differences presented as percentages with 95% confidence intervals. Between-group differences for repeated measurements over time will be assessed using a two-way analysis of variance, provided that the assumptions regarding outliers, normality of distribution of the dependent variable (using the Shapiro-Wilks test) and homogeneity of variance (using Levine’s test) are all met. If there is significant (>5%) missing data for the primary outcome, a sensitivity analyses will be conducted assuming that all patients for whom primary outcome data was missing either meet or do not meet the primary outcome. The type one error rate will be set at the level of 0.05. Analyses were conducted using STATA version 15.0 (Statacorp, TX, US).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
7/03/2022
Actual
12/08/2022
Date of last participant enrolment
Anticipated
28/01/2023
Actual
Date of last data collection
Anticipated
28/02/2023
Actual
Sample size
Target
60
Accrual to date
34
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 21227 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 21228 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [3] 21229 0
The Northern Beaches Hospital - Frenchs Forest
Recruitment postcode(s) [1] 36098 0
2086 - Frenchs Forest
Recruitment postcode(s) [2] 36096 0
2170 - Liverpool
Recruitment postcode(s) [3] 36097 0
2560 - Campbelltown

Funding & Sponsors
Funding source category [1] 310255 0
Government body
Name [1] 310255 0
South West Sydney Local Health District
Country [1] 310255 0
Australia
Primary sponsor type
Government body
Name
South West Sydney Local Health District
Address
Locked Bag 7279
LIVERPOOL BC
NSW 1871
Country
Australia
Secondary sponsor category [1] 311351 0
None
Name [1] 311351 0
Address [1] 311351 0
Country [1] 311351 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309927 0
South West Sydney Local Health District Human Research and Ethics Committee
Ethics committee address [1] 309927 0
Research Directorate
Locked Bag 7279
Eastern Campus
Liverpool BC NSW 1871
Ethics committee country [1] 309927 0
Australia
Date submitted for ethics approval [1] 309927 0
31/12/2021
Approval date [1] 309927 0
05/04/2022
Ethics approval number [1] 309927 0

Summary
Brief summary
A small number of patients presenting to emergency departments need intubation, a process to place a tube in their windpipe to protect their airway, and allow breathing support with a ventilator. Drugs are used to ensure that they are unconscious and to relax their muscles to make placement of the tracheal tube possible, but these drugs can cause changes to vital signs such as pulse and blood pressure, which could worsen their condition. Ketamine is often used as a sedative agent for intubation, and an opioid (morphine-like) drug is sometimes used to try and normalise the blood pressure during the procedure. Fentanyl is the most commonly used opioid for this purpose, but another drug called alfentanil is theoretically a better choice. In this clinical trial, we intend to randomise patients to receive equivalent doses of either fentanyl or alfentanil, in a blinded fashion, as part of a drug regimen with ketamine and a muscle relaxant called rocuronium.

The study aims to test the null hypothesis that there is no difference in the outcomes measured between fentanyl and alfentanil.
Trial website
N/A
Trial related presentations / publications
N/A
Public notes

Contacts
Principal investigator
Name 115866 0
Dr Ian Ferguson
Address 115866 0
Liverpool Hospital
Locked Bag 7103
Liverpool BC
NSW 1871
Country 115866 0
Australia
Phone 115866 0
+61287383950
Fax 115866 0
Email 115866 0
ian.ferguson@health.nsw.gov.au
Contact person for public queries
Name 115867 0
Dr Ian Ferguson
Address 115867 0
Liverpool Hospital
Locked Bag 7103
Liverpool BC
NSW 1871
Country 115867 0
Australia
Phone 115867 0
+61 287383950
Fax 115867 0
Email 115867 0
ian.ferguson@health.nsw.gov.au
Contact person for scientific queries
Name 115868 0
Dr Ian Ferguson
Address 115868 0
Liverpool Hospital
Locked Bag 7103
Liverpool BC
NSW 1871
Country 115868 0
Australia
Phone 115868 0
+61 287383950
Fax 115868 0
Email 115868 0
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?
De-identified data will be provided to other researchers with a valid clinical question for which ethical approval has been granted.
The data shared will be limited to that required by the study protocol of the requesting investigator, and may include all de-identified individual participant data collected if justified in the opinion of the investigation team.
When will data be available (start and end dates)?
Following publication of the study manuscript, until data destruction (15 years following completion in the current regulatory environment);
Available to whom?
Researchers with a valid clinical question, who have had ethical approval granted for their study.
Available for what types of analyses?
Systematic reviews or meta-analysis.
How or where can data be obtained?
Contacting the principal investigator (ian.ferguson@health.nsw.gov.au) by email.


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
No additional documents have been identified.