Paramedic-administered pain relief comparing ketamine and morphine in trauma
| ISRCTN | ISRCTN14124474 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14124474 |
| EudraCT/CTIS number | 2020-000154-10 |
| IRAS number | 1003404 |
| Secondary identifying numbers | CPMS 46938, IRAS 1003404 |
- Submission date
- 11/09/2020
- Registration date
- 22/10/2020
- Last edited
- 07/04/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Other
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 November 2023
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
Contact information
Scientific
Warwick Clinical Trials Unit
Gibbet Hill Campus
University of Warwick
Gibbet Hill Road
Coventry
CV4 7AL
United Kingdom
| Phone | +44 (0)2476 150478 |
|---|---|
| packman@warwick.ac.uk |
Scientific
Chief Investigator
Warwick Clinical Trials Unit
Gibbet Hill Campus
University of Warwick
Gibbet Hill Road
Coventry
CV4 7AL
United Kingdom
| Phone | +44 (0)2476 528039 |
|---|---|
| m.a.smyth@warwick.ac.uk |
Study information
| Study design | Randomized; Both; Design type: Treatment, Drug, Health Economic |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Paramedicine |
| Study type | Treatment |
| Participant information sheet | This will be made available on the trial website |
| Scientific title | Paramedic Analgesia Comparing Ketamine and MorphiNe in trauma (PACKMaN) |
| Study 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(s) | Approved 01/09/2020, West of Scotland Research Ethics Committee (Ward 11, Dykebar Hospital, Grahamston Road, Paisley, PA2 7DE, UK; +44 (0)141 3140212; wosrec1@ggc.scot.nhs.uk), ref: 20/WS/0126 |
| 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 |
| 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 study start date | 16/04/2018 |
| Overall study end date | 30/11/2023 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 16 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 446; UK Sample Size: 446 |
| Total final enrolment | 458 |
| Participant inclusion criteria | 1. Age ≥16 years 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 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 | 11/11/2021 |
| Recruitment end date | 31/05/2023 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Waterfront Business Park
Waterfront Way
Brierley Hill
DY5 1LX
United Kingdom
Brindley Way
Wakefield 41 Business Park
Wakefield
WF2 0XQ
United Kingdom
Sponsor information
University/education
Research and Impact Services
University House
Coventry
CV4 8UW
England
United Kingdom
| Phone | +44 (0)2476575732 |
|---|---|
| sponsorship@warwick.ac.uk |
Funders
Funder type
Government
No information available
Results and Publications
| Intention to publish date | 15/12/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Published as a supplement to the results publication |
| 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 plan | All data generated or analysed during this study will be included in the subsequent results publication |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No | ||
| Statistical Analysis Plan | version 1.0 | 14/06/2023 | 08/11/2023 | No | No |
| Protocol article | 24/11/2023 | 27/11/2023 | Yes | No | |
| Plain English results | 07/04/2025 | No | Yes | ||
| Results article | 05/04/2025 | 07/04/2025 | Yes | No | |
| Statistical Analysis Plan | version 2.0 | 14/02/2024 | 07/04/2025 | No | No |
Additional files
Editorial Notes
07/04/2025: A publication reference, SAP (version 2.0) and summary results were added.
30/09/2024: The intention to publish date was changed from 15/09/2024 to 15/12/2024.
29/07/2024: The intention to publish date was changed from 29/07/2024 to 15/09/2024.
14/06/2024: The intention to publish date was changed from 30/06/2024 to 29/07/2024.
27/11/2023: Publication reference added.
08/11/2023: The following changes were made:
1. Statistical analysis plan added.
2. The total final enrolment was added.
11/05/2023: The contact confirmed the record is up to date.
08/02/2023: The study setting has been changed from ‘Other’.
09/12/2022: The following changes were made to the trial record:
1. The recruitment start date was changed from 01/05/2021 to 11/11/2021.
2. The recruitment end date was changed from 31/12/2022 to 31/05/2023.
3. The overall end date was changed from 30/06/2023 to 30/11/2023.
4. The intention to publish date was changed from 30/06/2024 to 30/06/2024.
5. The plain English summary was updated to reflect these changes.
09/03/2022: The following changes were made to the trial record:
1. The participant level data sharing plan was added.
2. The trial website was added.
07/02/2022: The following changes have been made:
1. The recruitment end date has been changed from 28/02/2022 to 31/12/2022.
2. The overall trial end date has been changed from 31/08/2022 to 30/06/2023 and the plain English summary has been updated to reflect this change.
3. The intention to publish date has been changed from 31/08/2023 to 30/06/2024.
21/12/2020: The following changes have been made:
1. The recruitment start date has been changed from 01/11/2020 to 01/05/2021.
2. The ethics approval information has been added.
11/09/2020: Trial's existence confirmed by the NIHR.
