Prehospital Analgesia INtervention Trial (PAIN) (PAIN)

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 or HR ≥115) and an indication for pain management, comparing patient centered outcomes following prehospital administration of ketamine hydrochloride versus fentanyl citrate.

Study Overview

• Status: Recruiting
• Conditions: Traumatic Injury
• Intervention / Treatment: Drug: Ketamine Hydrochloride; Drug: Fentanyl Citrate

• Study Type: Interventional
• Enrollment (Estimated): 994
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jason Sperry, MD; Phone Number: 412-802-8270; Email: sperryjl@upmc.edu

Study Locations

• United States
  • California
    • San Diego, California, United States, 92103
      • Recruiting
      • University of California, San Diego
      • Contact: Laura Haines, MD; Phone Number: 619-543-7200; Email: lhaines@health.ucsd.edu
    • San Francisco, California, United States, 94110
      • Recruiting
      • Zuckerberg San Francisco General Hospital
      • Contact: Lucy Kornblith, MD; Phone Number: 415-609-6924; Email: Lucy.Kornblith@ucsf.edu
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Recruiting
      • Cooper University Health Care
      • Contact: Tanya Egodage; Phone Number: 856-342-3341; Email: egodage-tanya@cooperhealth.edu
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Recruiting
      • Atrium Health and Carolinas Medical Center
      • Contact: Addison May, MD; Phone Number: 704 446-2504; Email: addison.may@atriumhealth.org
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Recruiting
      • University of Cincinnati
      • Contact: Jason McMullan, MD; Phone Number: 513-675-3072; Email: jason.mcmullan@uc.edu
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • University of Pittsburgh
      • Contact: Jason Sperry, MD; Phone Number: 412-647-3065; Email: sperryjl@upmc.edu
      • Principal Investigator: Jason Sperry, MD
    • Pittsburgh, Pennsylvania, United States, 15212
      • Recruiting
      • Allegheny Health Network (AHN) Allegheny General Hospital
      • Contact: Philip Nawrocki, MD; Phone Number: 4124876590; Email: philip.nawrocki@ahn.org
    • Sayre, Pennsylvania, United States, 18840
      • Recruiting
      • Guthrie Robert Packer Hospital
      • Contact: Jon Rittenberger, MD; Phone Number: 570-887-4318; Email: Jon.Rittenberger@guthrie.org
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Recruiting
      • University of Utah
      • Contact: Scott Youngquist, MD; Email: scott.youngquist@hsc.utah.edu
  • Vermont
    • Burlington, Vermont, United States, 05405
      • Recruiting
      • The University of Vermont Larner College of Medicine
      • Contact: Daniel Wolfson, MD, FACEP, FAEMS; Phone Number: 802-847-2434; Email: daniel.wolfson@uvmhealth.org
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53266
      • Suspended
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Transport after injury to a participating PAIN Trauma center
• 2. Patient with compensated shock as defined by Shock Index (SI) ≥0.9 or Heart Rate (HR) ≥115.
• 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
• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketamine Hydrochloride; 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 approximately 15 minutes if the subject has a qualifying pain score, there are no contraindications to pain medication per local protocol, and no exclusion criteria have been met.	Drug: Ketamine Hydrochloride; ketamine hydrochloride 2.5mg/ml packaged in pre-filled syringe
Active Comparator: Fentanyl Citrate; 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 approximately 15 minutes if the subject has a qualifying pain score, there are no contraindications to pain medication per local protocol, and no exclusion criteria have been met.	Drug: Fentanyl Citrate; fentanyl citrate 10mcg/ml packaged in pre-filled syringe

What is the study measuring?

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
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
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
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
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
Hypoxia	incidence of hypoxia in the prehospital environment	from initial administration of PAIN prehospital analgesia through hospital arrival
Hypotension	incidence of hypotension in the prehospital environment	from initial administration of PAIN study prehospital analgesia through hospital arrival
Need for airway management	need for airway management in the prehospital environment	from initial administration of PAIN study 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 PAIN study prehospital analgesia through hospital arrival
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 PAIN study prehospital analgesia through hospital arrival
24 hour opioid use	total 24 hour opioid use	from initial administration of PAIN study 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 PAIN study prehospital analgesia through hospital arrival
Survival to hospital discharge	survival to hospital discharge	administration of PAIN study 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 PAIN study 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 PAIN study prehospital analgesia through hospital discharge or death up to 30 days

Collaborators and Investigators

• Sponsor: Jason Sperry
• Collaborators: United States Department of Defense
• Investigators: Principal Investigator: Jason Sperry, MD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2023
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2029

Study Registration Dates

• First Submitted: May 24, 2022
• First Submitted That Met QC Criteria: June 24, 2022
• First Posted (Actual): June 29, 2022

Study Record Updates

• Last Update Posted (Actual): March 9, 2026
• Last Update Submitted That Met QC Criteria: March 5, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: pain; shock; Trauma; ketamine hydrochloride; fentanyl citrate
• Additional Relevant MeSH Terms: Neurologic Manifestations; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain; Wounds and Injuries; Shock; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrocarbons; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Piperidines; Ketamine; Fentanyl
• Other Study ID Numbers: STUDY22010164; HT9425-25-F-0041 (Other Grant/Funding Number: Department of Defense)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data may be shared with the funding agency as well as other researchers upon request to the Principal Investigator
• IPD Sharing Time Frame: Data will become available after publication of the primary manuscript
• IPD Sharing Access Criteria: Requests for data will be submitted in writing and reviewed by the Principal Investigator.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No