Condition category
Not Applicable
Date applied
11/09/2020
Date assigned
22/10/2020
Last edited
22/10/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Pain after an injury is common. The strongest painkiller that UK paramedics routinely give for severe pain is morphine. Morphine can be slow to work and may cause side effects such as vomiting, drowsiness or low blood pressure. Because of this morphine might not be the best pain killer to use. Ketamine is another strong painkiller. It acts very quickly to reduce pain and may have fewer unwanted side effects. In some parts of the world (Australia, Canada and America) paramedics are allowed to give ketamine, rather than morphine, to patients who have severe pain following injury. Research from these countries tells us that ketamine might be better than morphine, but the research isn’t good enough to be sure. The aim of this study is to investigate if ketamine is better than morphine for severe pain after injury and to decide if it suitable for use by UK paramedics.

Who can participate?
If an ambulance is called to a patient with severe pain after an injury, paramedics will check to see if the patient is suitable for this study. They will consider patients who are 16 years of age or over, have suffered an injury which is causing severe pain, and are able to have a strong pain killer administered by injection.

What does the study involve?
Eligible participants will be enrolled by the attending paramedic and randomly allocated to be treated with either ketamine or morphine. After 3 and 6 months participants will be asked to complete questionnaires about their recovery. Data will be collected from the ambulance services about the patients' injury and treatment, and about their stay from the hospital where the participant was taken.

What are the possible benefits and risks of participating?
The potential risk for the patient would be a reaction to ketamine or morphine. This will be minimised by paramedics following the guidelines in the trial protocol for administering ketamine and morphine. The study provides naloxone and midazolam for treating the side effects of morphine and ketamine. Paramedics already use morphine so are trained in administering this. Training will be provided on the use of ketamine. Training will also be provided on how to randomise the patient and administer ketamine or morphine. There may be a slight burden to participants completing the follow up at 3 and 6 months. This follow-up is most likely to be completed via a telephone call with one of the researchers who can talk a participant through the questionnaires, explaining and answering any questions they have. There is a risk the patient may feel some distress when completing the questionnaires as it may remind them of their injury. The researchers will provide contact details for the participant to speak to the PI and research team to gain support. If they answer the questionnaires with a researcher via the telephone, the researcher will be able to support the participant at the time of discussion.

Where is the study run from?
Warwick Clinical Trials Unit (UK)

When is the study starting and how long is it expected to run for?
April 2018 to August 2022

Who is funding the study?
National Institute for Health Research Health Technology Assessment (UK)

Who is the main contact?
Charlotte Scomparin
packman@warwick.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Charlotte Scomparin

ORCID ID

Contact details

Warwick Clinical Trials Unit
Gibbet Hill Campus
University of Warwick
Gibbet Hill Road
Coventry
CV4 7AL
United Kingdom
+44 (0)2476 150478
packman@warwick.ac.uk

Type

Scientific

Additional contact

Dr Michael Smyth

ORCID ID

Contact details

Chief Investigator
Warwick Clinical Trials Unit
Gibbet Hill Campus
University of Warwick
Gibbet Hill Road
Coventry
CV4 7AL
United Kingdom
+44 (0)2476 528039
m.a.smyth@warwick.ac.uk

Additional identifiers

EudraCT number

2020-000154-10

ClinicalTrials.gov number

Nil known

Protocol/serial number

CPMS 46938, IRAS 1003404

Study information

Scientific title

Paramedic Analgesia Comparing Ketamine and MorphiNe in trauma (PACKMaN)

Acronym

PACKMaN

Study hypothesis

Ketamine is superior to morphine for the management of acute severe pain from traumatic injury treated by NHS paramedics.

Ethics approval

Approval pending, REC ref: 20/WS/0126

Study design

Randomized; Both; Design type: Treatment, Drug, Health Economic

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Treatment

Patient information sheet

This will be made available on the trial website

Condition

Analgesia

Intervention

Participants are randomized on a 1:1 basis between ketamine and morphine, stratified by ambulance services. Specially prepared, sequentially numbered treatment packs containing identical ampoules of either morphine (comparator) or ketamine (intervention) will be provided to each ambulance service. Numbered study drug packs in a pre-randomized sequence, will be carried by participating ambulance paramedics. Participants will be randomised by opening the pack.

The study drug can be administered by the intravenous (IV) or intraosseous (IO) routes.
Paramedics will dilute the ampoule of study drug with 9 ml of 0.9% sodium chloride in a 10 ml syringe. (Syringe 1).
Syringe 1 will be administered by slow IV/IO injection over 4 to 5 minutes. Titrate to effect (up to the full 10ml being administered) aiming to give the minimal effective dose.
Paramedics will observe the participant for at least 5 minutes for effect. If pain is not relieved after syringe 1 has been administered, they prepare a second syringe by diluting a further ampoule of study drug with 9 ml of 0.9% sodium chloride in a 10 ml syringe (Syringe 2).
They administer 2 ml aliquots from Syringe 2 by slow IV/IO injection every 5 minutes and repeat further 2 ml aliquots every 5 minutes until adequate pain relief is achieved.
If after adequate pain relief is achieved the person experiences breakthrough pain, further 2 ml aliquots may be administered every 5 minutes.
The maximum dose that can be administered under this protocol for ketamine is 30 mg (two ampoules) and for morphine is 20 mg (two ampoules).

Participants will be followed up for 6 months.

Intervention type

Other

Phase

Phase III

Drug names

Primary outcome measure

Effectiveness of pain relief from randomisation to arrival at hospital as measured by Sum of Pain Intensity Difference (SPID) score (using a 0-10 numerical rating scale); Timepoint(s): Arrival at hospital.

Secondary outcome measures

1. Effectiveness of pain relief and overall patient experience from randomisation to arrival at hospital measured using the following at baseline:
1.1. Total Pain Relief (TOTPAR) score
1.2. Time to perceptible analgesia
1.3. Time to meaningful analgesia
1.4. Time to peak analgesia
1.5. Duration of analgesia
1.6. Requirement for rescue analgesia
1.7. Proportion of patients with a pain intensity score below 4/10 (0-10 numerical rating scale (NRS)) on arrival at hospital
1.8. Vital signs (temperature, blood pressure, pulse rate, respiration rate)
1.9. Patient Global Impression of Change on arrival at hospital
2. Incidence of side effects and adverse events measured by recording side effects and adverse events at baseline to 30 days post IMP administration:
2.1. Airway: vomiting, aspiration, advanced airway management
2.2. Respiratory: desaturation, need for ventilatory support
2.3. Cardiovascular: arrhythmia, hypotension and hypertension
2.4. Neurologic: sedation, excitatory movements, adverse behavioural reactions
2.5. Other: allergic reaction, serious unexpected serious adverse reactions
3. Resource use measured by recording the following information at baseline and from hospital data:
3.1. Ambulance job cycle time (scene arrival to arrival at hospital)
3.2. Number of ambulance resources (technicians, paramedics, doctors and vehicles) in attendance
3.3. Cumulative IMP doses administered
3.4. CT scan use
3.5. Hospital or ICU admission
3.6. Length of stay ED, ICU, Hospital
4. Longer-term outcomes measured using the following at 3 and 6 months post-randomization:
4.1. Chronic pain measured using BPI-SF
4.2. Health-related quality of life measured using EQ-5D-5L and CSRI
4.3. Cost-effectiveness expressed in terms of incremental cost per quality-adjusted life-year (QALY) gained using EQ-5D 5L and CSRI

Overall trial start date

16/04/2018

Overall trial end date

31/08/2022

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Age ≥16
2. Patient reports a pain score ≥7/10 on a 0-10 NRS following acute traumatic injury
3. Vascular access obtained
4. Determined by a paramedic to require IV morphine or equivalent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 446; UK Sample Size: 446

Participant exclusion criteria

1. Known or suspected pregnancy
2. Unable to articulate severity of pain using the 0-10 NRS
3. Lack of capacity due to a reason other than pain
4. Ketamine or opioid analgesia prior to randomisation
5. Contraindication to either ketamine or morphine*
6. Patient declines participation
7. Known prisoner

Recruitment start date

01/11/2020

Recruitment end date

28/02/2022

Locations

Countries of recruitment

United Kingdom

Trial participating centre

West Midlands Ambulance Service NHS Foundation Trust
Millennium Point Waterfront Business Park Waterfront Way
Brierley Hill
DY5 1LX
United Kingdom

Trial participating centre

Yorkshire Ambulance Service NHS Trust
Trust Headquarters Brindley Way Wakefield 41 Business Park
Wakefield
WF2 0XQ
United Kingdom

Sponsor information

Organisation

University of Warwick

Sponsor details

Research and Impact Services
University House
Coventry
CV4 8UW
United Kingdom
+44 (0)2476575732
sponsorship@warwick.ac.uk

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC); Grant Codes: NIHR128086

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

1. The protocol will be published via NIHR NETSCC
2. Planned publication in a high-impact peer-reviewed journal within 1 year of the end of the trial

IPD sharing statement
The data-sharing plans for the current study are unknown and will be made available at a later date

Intention to publish date

31/08/2023

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

11/09/2020: Trial's existence confirmed by the NIHR.