Title: A randomised controlled trial of Paramedic Analgesia Comparing Ketamine and MorphiNe in trauma (PACKMaN)
Funder: Department of Health and Social Care

Abstract: AIM: To decide if paramedics should use the pain killer ketamine, rather than morphine, to relieve severe pain in patients with injuries._x000D_ _x000D_ BACKGROUND: Pain after an injury is common. The strongest pain killer that UK paramedics are routinely able to give is morphine. This can be slow to work and may cause side effects such as vomiting, drowsiness or low blood pressure. In some parts of the world (Australia, Canada and America) paramedics use a different pain killer called ketamine. Research from these countries tells us that ketamine might be better than morphine, but the research isn’t good enough for us to be sure. We need to investigate if ketamine is suitable for use by paramedics working in UK ambulance services._x000D_ _x000D_ DESIGN: We will train paramedics to use ketamine safely and in procedures related to the trial. 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 our study. We will consider patients who:_x000D_ ? Are 16 years of age or over_x000D_ ? Have suffered an injury which is causing severe pain_x000D_ ? Are able to have a strong pain killer administered through by injection_x000D_ If the patient agree to take part, the paramedic will record how bad their pain is before treatment. The paramedic will then open a trial drug pack and administer the pain killer provided. Half of the drug packs will contain the pain killer, ketamine and half will contain the pain killer morphine. This will ensure an equal number of patients receive each treatment. The patient and paramedic will not know which drug is in the drug pack (sometimes called a double-blind study). This is important as it allows an unbiased assessment of how well each the drug works. During the ambulance journey to hospital, if pain does not get better the paramedic will be able to give_x000D_ more of the pain killer. The paramedics will regularly monitor how well the pain killer is working. We will compare how well each of the pain killers worked to decide if ketamine is better than morphine for reducing severe pain after an injury._x000D_ _x000D_ PATIENT AND PUBLIC INVOLVEMENT: One of our research team is a member of the public who suffered serious injuries and has experience of many different pain treatments. In the past he has worked with other patients to help improve research in this area. He will work with us to guide the research and make sure it is focused on what is important to patients. He will help design, interpret and communicate our research and will play an important role in developing the final recommendations for new treatment guidelines for paramedics. _x000D_ _x000D_ DISSEMINATION: We will share the study findings with paramedics, patients and those responsible for organizing and funding NHS Ambulance Services. We will do this through publishing our findings in medical journals and present them at meetings for doctors, nurses, paramedics and patients. We will highlight key messages from the research through patient stories. We will develop an easy to understand infographic (picture) which summarises the study findings. We will distribute this and a trial summary widely using our networks, via the internet and social media.

Lay abstract: RESEARCH QUESTION _x000D_ Is ketamine superior to morphine for the management of acute severe pain from traumatic injury treated by NHS paramedics?_x000D_ _x000D_ BACKGROUND_x000D_ Pain from severe trauma is poorly treated. NHS Paramedics have a limited formulary to treat severe pain. Ketamine may be an ideal prehospital drug due to its rapid onset of action, superior analgesic properties and safety. NICE identified the need to determine the clinical and cost effectiveness of ketamine against standard care (morphine). _x000D_ _x000D_ AIM_x000D_ To deliver a pragmatic, blinded, individually randomised, controlled trial, in two NHS Ambulance Trusts (informed by an internal pilot), which will determine the clinical and cost effectiveness of ketamine and morphine, among adult patients, with severe pain following trauma and who are attended by paramedics._x000D_ _x000D_ PRIMARY OBJECTIVE_x000D_ To determine whether paramedic administered ketamine or morphine provides more effective pain relief for patients reporting severe pain following trauma._x000D_ _x000D_ SECONDARY OBJECTIVE_x000D_ To assess the effects of paramedic administered ketamine or morphine on overall pain relief / patient experience, tolerability, resource used, longer term outcomes and cost effectiveness. _x000D_ _x000D_ DESIGN_x000D_ Pragmatic, individually randomised, controlled, blinded trial, with economic evaluation._x000D_ _x000D_ SETTING_x000D_ 2 NHS Ambulance Services_x000D_ _x000D_ POPULATION_x000D_ Adult patients with severe pain following trauma, judged by the paramedic as requiring treatment with IV morphine. _x000D_ _x000D_ INCLUSION CRITERIA _x000D_ 1. Age >16_x000D_ 2. Patient reports severe pain due to an acute traumatic injury _x000D_ 3. Vascular access obtained_x000D_ _x000D_ EXCLUSION CRITERIA_x000D_ 1. Known or suspected pregnancy_x000D_ 2. Unable to articulate severity of pain using the 0-10 numerical rating scale_x000D_ 3. Ketamine or opioid analgesia received prior to screening_x000D_ 4. Contraindication to either ketamine or morphine_x000D_ 5. Patient declines participation_x000D_ _x000D_ RANDOMISATION_x000D_ Specially prepared, sequentially numbered treatment packs containing ampoules of either morphine or ketamine which are identical in appearance. Allocation will be concealed from study personnel, ambulance staff and patients._x000D_ _x000D_ INTERVENTION_x000D_ Ketamine hydrochloride._x000D_ _x000D_ COMPARATOR_x000D_ Morphine sulphate._x000D_ _x000D_ PRIMARY OUTCOME_x000D_ Sum of Pain Intensity Difference (SPID) score_x000D_ _x000D_ SECONDARY OUTCOMES_x000D_ Effectiveness of pain relieve / overall patient experience from randomisation to hospital arrival Side effects and adverse events_x000D_ Resource use_x000D_ Longer term outcomes_x000D_ Cost effectiveness_x000D_ _x000D_ SAMPLE SIZE_x000D_ Using 1:1 randomisation, a power of 90%, significance level of 5% and a withdrawal/non-response rate of 2%, we require 526 subjects to detect a clinically relevant reduction of 1-point different (standard deviation=3.5) points on a 0-10 numeric pain scale._x000D_ _x000D_ TIMELINE_x000D_ Months 0-6: study protocol, regulatory approvals, IMP manufacture; 7-16 paramedic training; 7-12 internal pilot phase; 13-24: main trial recruitment; 10-30: follow-up; 31-36: analysis and reporting_x000D_ _x000D_ IMPACT AND DISSEMINATION: _x000D_ Our research will support evidence-based pain management guidelines for use by paramedics within NHS ambulance services. It will improve healthcare quality for patients with severe pain following trauma by engaging clinicians, patients, ambulance services and policy makers to provide better care and optimising limited health resources. We will disseminate the findings widely making use of infographic summaries, patient stories, publications, presentations, press releases and social med

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: INJURIES AND ACCIDENTS