Traumatic InjuryPhase 3PAINNCT05437575
Prehospital Analgesia INtervention Trial (PAIN)
A Phase 3 study testing Ketamine Hydrochloride and Fentanyl Citrate in people with Traumatic Injury, run by Jason Sperry at 11 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Traumatic Injury
- What is being tested?
- Ketamine Hydrochloride and Fentanyl Citrate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 994 participants
- Where
- 11 sitesUnited States
- Study dates
- 27 Nov 2023to Jul 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
11 sites in 1 country. Contact the study team or a site near you to ask about taking part.
11 sites in 1 country
United States11 sites, 10 recruiting
- Recruiting
The University of Vermont Larner College of Medicine
Burlington, Vermont, 05405
Daniel Wolfson, MD, FACEP, FAEMS, 802-847-2434, daniel.wolfson@uvmhealth.org
- Recruiting
Cooper University Health Care
Camden, New Jersey, 08103
Tanya Egodage, 856-342-3341, egodage-tanya@cooperhealth.edu
- Recruiting
Atrium Health and Carolinas Medical Center
Charlotte, North Carolina, 28203
Addison May, MD, 704 446-2504, addison.may@atriumhealth.org
- Recruiting
University of Cincinnati
Cincinnati, Ohio, 45267
Jason McMullan, MD, 513-675-3072, Jason.McMullan@uc.edu
- Suspended
Medical College of Wisconsin
Milwaukee, Wisconsin, 53266
- Recruiting
Allegheny Health Network (AHN) Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
Philip Nawrocki, MD, 4124876590, philip.nawrocki@ahn.org
- Recruiting
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
Jason Sperry, MD, 412-647-3065, sperryjl@upmc.edu
Jason Sperry, MD
- Recruiting
University of Utah
Salt Lake City, Utah, 84132
Scott Youngquist, MD, scott.youngquist@hsc.utah.edu
- Recruiting
University of California, San Diego
San Diego, California, 92103
Laura Haines, MD, 619-543-7200, lhaines@health.ucsd.edu
- Recruiting
Zuckerberg San Francisco General Hospital
San Francisco, California, 94110
Lucy Kornblith, MD, 415-609-6924, Lucy.Kornblith@ucsf.edu
- Recruiting
Guthrie Robert Packer Hospital
Sayre, Pennsylvania, 18840
Jon Rittenberger, MD, 570-887-4318, Jon.Rittenberger@guthrie.org
About this study
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.
- Conditions
- Traumatic Injury
- Being tested
- Ketamine Hydrochloride, Fentanyl Citrate
- Keywords
- Trauma, ketamine hydrochloride, fentanyl citrate, shock, pain
- Medical subject headings
- Wounds and Injuries, Shock, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketamine HydrochlorideDrug
ketamine hydrochloride 2.5mg/ml packaged in pre-filled syringe
Fentanyl CitrateDrug
fentanyl citrate 10mcg/ml packaged in pre-filled syringe
| Study group | Role | What they receive |
|---|---|---|
| Ketamine Hydrochloride | Experimental | 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. Receives: Drug: Ketamine Hydrochloride |
| Fentanyl Citrate | Active comparator | 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. Receives: Drug: Fentanyl Citrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
24-hour mortality
All cause mortality within 24 hours from time of trauma bay arrival
Measured: trauma bay arrival through 24 hours
Secondary outcomes (16)
Hypoxia
incidence of hypoxia in the prehospital environment
Measured: from initial administration of PAIN prehospital analgesia through hospital arrival
Hypotension
incidence of hypotension in the prehospital environment
Measured: from initial administration of PAIN study prehospital analgesia through hospital arrival
Need for airway management
need for airway management in the prehospital environment
Measured: 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.
Measured: from initial administration of PAIN study 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.
Measured: 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.
Measured: from initial administration of PAIN study prehospital analgesia through hospital arrival
24 hour opioid use
total 24 hour opioid use
Measured: 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
Measured: from initial administration of PAIN study prehospital analgesia through hospital arrival
Survival to hospital discharge
survival to hospital discharge
Measured: 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
Measured: 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
Measured: from administration of PAIN study 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
Measured: 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
Measured: 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)
Measured: 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)
Measured: 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)
Measured: At 3 and 6 months (+/- 1 month) after hospital arrival
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2022
- Study start27 Nov 2023
- Primary completionJul 2028 (estimated)
- Study completionJul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Traumatic InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel Assignment
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 994 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jason Sperry
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense
- Responsible party
- Sponsor-investigator, Jason Sperry, University of Pittsburgh
- Investigators
- Jason Sperry, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05437575
- Sponsor's protocol ID
- STUDY22010164
- Other IDs
- HT9425-25-F-0041
- Acronym
- PAIN
- Status last verified
- Mar 2026
- First submitted
- 24 May 2022
- Last updated
- 9 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified data may be shared with the funding agency as well as other researchers upon request to the Principal Investigator
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prehospital Analgesia INtervention Trial (PAIN)
- ClinicalTrials.gov ID
- NCT05437575
- Acronym / sponsor ID
- PAIN / STUDY22010164
- Conditions
- Traumatic Injury
- Keywords
- Trauma, ketamine hydrochloride, fentanyl citrate, shock, pain
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 994 participants (estimated)
- Lead sponsor
- Jason SperryUniversity, hospital or other
- Collaborators
- United States Department of Defense
- Study start
- 27 Nov 2023 (actual)
- Primary completion
- Jul 2028 (estimated)
- Study completion
- Jul 2029 (estimated)
- First posted
- 29 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
- Model description
- Parallel Assignment
| Arm | Type | Receives |
|---|---|---|
| Ketamine Hydrochloride | Experimental | Drug: Ketamine Hydrochloride2 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. |
| Fentanyl Citrate | Active comparator | Drug: Fentanyl Citrate2 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketamine Hydrochlorideketamine hydrochloride 2.5mg/ml packaged in pre-filled syringe | Drug | Ketamine Hydrochloride |
| Fentanyl Citratefentanyl citrate 10mcg/ml packaged in pre-filled syringe | Drug | Fentanyl Citrate |
Primary outcome
24-hour mortality
Time frame: trauma bay arrival through 24 hours
All cause mortality within 24 hours from time of trauma bay arrival
16 secondary outcomes
Hypoxia
Time frame: from initial administration of PAIN prehospital analgesia through hospital arrival
Hypotension
Time frame: from initial administration of PAIN study prehospital analgesia through hospital arrival
Need for airway management
Time frame: from initial administration of PAIN study prehospital analgesia through hospital arrival
Prehospital pain assessment following analgesia
Time frame: from initial administration of PAIN study prehospital analgesia through hospital arrival
Trauma bay arrival pain score
Time frame: 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
Time frame: from initial administration of PAIN study prehospital analgesia through hospital arrival
24 hour opioid use
Time frame: from initial administration of PAIN study prehospital analgesia through 24 hours
Incidence of prehospital adverse events
Time frame: from initial administration of PAIN study prehospital analgesia through hospital arrival
Survival to hospital discharge
Time frame: administration of PAIN study prehospital analgesia through hospital discharge or death up to 30 days
Ventilator free days
Time frame: from administration of PAIN study prehospital analgesia through hospital discharge or death up to 30 days
Intensive Care Unit free days
Time frame: from administration of PAIN study prehospital analgesia through hospital discharge or death up to 30 days
Long term opioid use
Time frame: 3 months (+/- 1 month) and 6 months (+/- 1 month) following trauma admission
Hospital length of stay
Time frame: from time of hospital admission to discharge
Baseline Pain/Anxiety/PTSD screening
Time frame: 0 hours to 2 weeks from time of hospital admission
Long term (6 month) outcome
Time frame: 6 months +/- 1 month following trauma admission
Long Term Pain Assessment
Time frame: At 3 and 6 months (+/- 1 month) after hospital arrival
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2026.
- Individual participant dataSharing planned: Yes. De-identified data may be shared with the funding agency as well as other researchers upon request to the Principal Investigator
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jason Sperry, MD principal investigator
University of Pittsburgh
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ketamine Hydrochloride and Fentanyl Citrate in people with Traumatic Injury, run by Jason Sperry at 11 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jason Sperry, MD (412-802-8270, sperryjl@upmc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
24-hour mortality (time frame: trauma bay arrival through 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2026.