Prehospital Analgesia INtervention Trial (PAIN)

Study Overview
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Brief Summary
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The Prehospital Analgesia INtervention trial (PAIN) is a proposed 4 year (3-year enrollment) multicenter, prehospital, randomized, double-blind, clinical trial that will enroll approximately 994 patients at select LITES Network sites. The objective is to perform a prospective, interventional, randomized trial among prehospital trauma patients with compensated shock (SI>0.9) and an indication for pain management, comparing patient centered outcomes following prehospital administration of ketamine hydrochloride versus fentanyl citrate.

Official Title
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Prehospital Analgesia INtervention Trial (PAIN)

Conditions
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Traumatic Injury

Intervention / Treatment
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* Drug: Ketamine Hydrochloride
* Drug: Fentanyl Citrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Trauma activation and transport from the scene of injury to a participating PAIN Trauma center Patient with compensated shock as defined by Shock Index (SI) >0.9 Intravenous pain medication indicated (CPOT>2, NRS>5) prior to arrival at the trauma center Exclusion Criteria: No IV access Age <18 years Females <50 years of age SBP>180 mmHg at time of enrollment Received pain medication prior to enrollment Advanced airway management prior to first dose administration Known allergy to fentanyl citrate or ketamine hydrochloride Known prisoner Objection to study voiced by subject or family member at scene Pain treatment contraindicated by local protocol Wearing a NO PAIN STUDY bracelet

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketamine Hydrochloride<br>2 blinded doses 2.5mg/ml ketamine hydrochloride in separately sealed pre-filled syringes Subjects will be administered the first dose over approximately 2 minutes via slow IV push. Pain assessment following administration will be obtained and recorded every 15 minutes. Redosing may occur after 15 minutes if indication for pain management remains and there are no adverse events | Drug: Ketamine Hydrochloride<br>* ketamine hydrochloride 2.5mg/ml packaged in pre-filled syringe<br>|
| Active Comparator: Fentanyl Citrate<br>2 blinded doses 10mcg/ml in separately sealed pre-filled syringes Subjects will be administered the first dose over approximately 2 minutes via slow IV push. Pain assessment following administration will be obtained and recorded every 15 minutes. Redosing may occur after 15 minutes if indication for pain management remains and there are no adverse events | Drug: Fentanyl Citrate<br>* fentanyl citrate 10mcg/ml packaged in pre-filled syringe<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24-hour mortality | All cause mortality within 24 hours from time of trauma bay arrival | trauma bay arrival through 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hypoxia | incidence of hypoxia in the prehospital environment | from initial administration of prehospital analgesia through hospital arrival | 
| Hypotension | incidence of hypotension in the prehospital environment | from initial administration of prehospital analgesia through hospital arrival | 
| Need for airway management | need for airway management in the prehospital environment | from initial administration of prehospital analgesia through hospital arrival | 
| Prehospital pain assessment following analgesia | prehospital pain assessment using Numeric Rating Scale (NRS)/Critical Care Pain Observational Tool (CPOT) scores. For Numeric Rating Scale, the patient rates their pain on a scale of 0 to 10 where 0 is no pain and 10 is the worst pain. The Critical Care Pain Observation Tool is used for patients who are intubated and cannot verbalize a pain score. Medical staff will observe the patient's behavior and score the patient's pain on a scale of 0 to 10, where 0 is no pain and 10 is the worst pain. | from initial administration of prehospital analgesia through hospital arrival | 
| Trauma bay arrival pain score | pain assessment using Numeric Rating Scale (NRS)/Critical Care Pain Observation Tool (CPOT) score. For Numeric Rating Scale, patients rate their pain on a scale of 0 to 10 where 0 is no pain and 10 is the worst pain. The Critical Care Pain Observation Tool is used for patients who are intubated and cannot verbalize a pain score. A nurse will observe behavior and score the patient's pain on a scale of 0 to 10 where 0 is no pain and 10 is the worst pain. | score assessed at time of arrival to trauma bay | 
| Number of analgesic doses necessary to reduce pain level to <5 NRS or CPOT less than 2 | Number of analgesic doses necessary to reduce pain level to <5 on Numeric Rating Scale or less than 2 on Critical Care Pain Observation Tool. For Numeric Rating Scale, the patient rates their pain on a scale of 0 to 10 where 0 is no pain and 10 is the worst pain. The Critical Care Pain Observation Tool is used for patients who are intubated and cannot verbalize a pain score. A nurse will observe behavior and score the patient's pain on a scale of 0 to 10 where 0 is no pain and 10 is the worst pain. | from initial administration of prehospital analgesia through hospital arrival | 
| 24 hour opioid use | total 24 hour opioid use | from initial administration of prehospital analgesia through 24 hours | 
| Incidence of prehospital adverse events | Incidence of adverse events of allergic reaction, emergence, laryngospasm, dysphoria, pruritus, and nausea | from initial administration of prehospital analgesia through hospital arrival | 
| Survival to hospital discharge | survival to hospital discharge | administration of prehospital analgesia through hospital discharge or death up to 30 days | 
| Ventilator free days | ventilator free days. Ventilator days are defined as number of days recorded to the first decimal spent on a mechanical ventilator subtracted from 30 | from administration of prehospital analgesia through hospital discharge or death up to 30 days | 
| Intensive Care Unit free days | number of days recorded to the first decimal spent admitted to the Intensive Care Unit subtracted rom 30 | from administration of prehospital analgesia through hospital discharge or death up to 30 days | 
| Long term opioid use | long term opioid use assessed at 3 and 6 months. Patients who consent to further participation will be contacted to determine if they continued to use opioids (yes/no) at 3 and 6 months following trauma admission | 3 months (+/- 1 month) and 6 months (+/- 1 month) following trauma admission | 
| Hospital length of stay | number of days recorded to the first decimal from hospital admission to discharge up to 30 days | from time of hospital admission to discharge | 
| Baseline Pain/Anxiety/PTSD screening | A subset of patients who consent to further participation will be assessed for Anxiety/PTSD using the Four-Item Patient Health Questionnaire (PHQ-4) for anxiety and depression, a two item pain severity scale (0=no pain to 10=worst pain), and the Injured Trauma Survivor Screen (ITSS) | 0 hours to 2 weeks from time of hospital admission | 
| Long term (6 month) outcome | A subset of patients who consent to further participation will be assessed for anxiety/depression/PTSD symptoms using the following tools: Generalized Anxiety Disorder (GAD-7), 8 item Patient Health Questionnaire (PHQ-8), and 8 item PTSD checklist (PCL-5) | 6 months +/- 1 month following trauma admission | 
| Long Term Pain Assessment | A subset of patients who consent to further participation will be assessed for long term pain using a modified Brief Pain Inventory (numerical scale rating 0-10) | At 3 and 6 months (+/- 1 month) after hospital arrival | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Trauma, ketamine hydrochloride, fentanyl citrate, shock, pain