RCT: Fentanyl Plus Ketamine Versus Fentanyl Alone for Acute Burn Pain

Evaluating the Safety, Efficacy and Opiate Sparing Effects of Low-Dose, Slow Infusion Ketamine as a Battlefield Analgesic for Acute Pain in Burn Wounds.

The Ketamine for Acute Pain in Burns study is a randomized, double-blind, parallel group trial (RCT) with active control (usual care) contrasting the efficacy and safety of "Ketamine Plus Opiate-based usual care" (O+K) with the safety and efficacy of the "Current Standard of Care". THe current standard of care is an opiate medication alone, Fentanyl (Usual Care-Opiate (UC-O), dose/timing as per Burn Center protocol).

Study Overview

• Status: Terminated
• Conditions: Acute Pain; Posttraumatic Stress Disorder; Wound Care
• Intervention / Treatment: Drug: ketamine; Drug: Fentanyl

Detailed Description

Department of Defense (DoD) and the U.S. Army Medical Research and Materiel Command (USAMRMC) are funding this RCT for the following reasons:

Primary Aims:

1. To evaluate the safety and efficacy of fentanyl (usual care) + placebo versus fentanyl + ketamine (low-dose, sub-anesthetic, slow-infusion) during twice daily burn wound care across a 7-day study period and 30 day outcome period.
2. To evaluate the opiate sparing effect of fentanyl (usual care) + placebo versus fentanyl + ketamine (low-dose, sub-anesthetic, slow-infusion) during the 7-day study period and 30 day outcome period.

and

Secondary Aims:

1. To determine the short and long term effect of the Ketamine Augmentation Condition versus the Usual Care Condition on symptoms and syndromes of posttraumatic stress disorder and of depression,
2. To evaluate several established and hypothesized moderators of the relationship between the Ketamine Augmentation Condition versus the Usual Care Condition on: 1) pain severity reported during wound care, 2) opiate use during wound care, 3) posttraumatic stress and 4) depression.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Burn Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Total Body Surface Area (TBSA) greater than or equal to 2%; Less than or equal to 40% TBSA
• English speaking
• pain in emergency room during initial wound evaluation (on admission) greater than 5 /10
• estimated length of stay greater than or equal to 5 days

Exclusion Criteria:

• requiring endotracheal intubation and sedation,
• severe hearing impairment,
• cognitive impairment status - Mini-Mental State Examination (MMSE) </=20,
• diminished capacity unable to provide informed consent;
• Past Medical History (PMH): insensate (eg. spinal cord injury, peripheral neuropathy)
• Safety: contraindication (e.g., potential drug interactions or medical comorbidities)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Fentanyl Plus Ketamine; Study drug group; Ketamine Loading Dose (Low Dose, Slow Infusion) =• 0.3 mg/kg; Initiated approximately 10 minutes before wound care start, pump set to deliver slowly over approximately 5 minutes, … Then,; Fentanyl Loading Dose (UC, injection) =• 1 mcg / kg. This is given to participants in both Group 1 and Group 2 initiated < 1 minute prior to wound care.; Ketamine (Study Drug, Infusion) = • 2.5 mcg/kg/min, Pump initiates infusion immediately after the fentanyl Loading Dose and continued for session duration. The nurse determines session end, then turns off infusion. Fentanyl PRN dose* = 1 mcg / kg. Provided when participant requires additional pain medication.	Drug: ketamine; Information included in arm descriptions; Other Names: STUDY DRUG GROUP (Fentanyl plus Ketamine); Drug: Fentanyl; Information included in arm descriptions; Other Names: USUAL CARE GROUP (Fentanyl plus saline/placebo)
ACTIVE_COMPARATOR: Fentanyl Plus Saline; Usual care group; Saline Loading Dose (Low Dose, Slow Infusion) =• An identical volume of saline as that in 0.3 mg/kg of ketamine. Initiated approximately 10 minutes before wound care start, pump set to deliver slowly over approximately 5 minutes, (i.e., same time/rate as STUDY DRUG GROUP receives ketamine loading dose), … Then, ...; Fentanyl Loading Dose (UC, injection) =• 1 mcg / kg: This is given to participants in both Group 1 and Group 2 initiated <1 minute prior to wound care.; Saline (Placebo, Infusion) = • Identical volume of fluid as that in 2.5 mcg/kg/min of ketamine; Pump initiates infusion immediately after the fentanyl Loading Dose and continued for session duration. The nurse determines session end, then turns off infusion. FENTANYL PRN DOSE = 1 mcg / kg. Provided when participant requires additional pain medication.	Drug: Fentanyl; Information included in arm descriptions; Other Names: USUAL CARE GROUP (Fentanyl plus saline/placebo)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Wound Care Pain	Average Pain across 14 sessions between the 2 groups and related outcome measures up to 40 days following study enrollment.	Up to 40 days
Trajectory of Mean Wound Care Session Pain Within Sessions	Trajectory of average pain within session	7-days, within session
Trajectory of Mean Wound Care Session Pain Across Sessions	Trajectory of average pain across 7 day study protocol	7-Days across sessions
Opiate Sparing Effect	Pro Re Nata (PRN) pain management or adjunct expressed in opiate equivalents (e.g., anxiolytic) or premed (e.g., non-protocol medications for pain, anxiety, etc); post-session (1 and 6 hours post session , e.g., pain, anxiolytic, etc).	37 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post Traumatic Stress Disorder (PTSD) Symptoms as Assessed by Davidson Trauma Scale	PTSD symptoms score as assessed by Davidson Trauma Scale consisting of 17 items (symptoms) with each item measured for severity and frequency. Each item is rated 0 - 4. Overall score ranges from 0 to 136, with higher scores indicating higher frequency and severity.	37 days
Depression Symptoms as Assessed by the Patient Health Questionnaire	Severity and trajectory of depression symptoms as assessed by the Patient Health Questionnaire (PHQ) 9. The questionnaire has 9 items with each rated from 0 to 3. Overall scores ranges from 0 to 27 with 1-4 being minimal depression, 5-9 being mild depression, 10-14 being moderate depression, 15-19 being moderately severe depression and 20-27 being severe depression.	37 days

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: United States Department of Defense; Congressionally Directed Medical Research Programs
• Investigators: Principal Investigator: James A Fauerbach, PhD, Johns Hopkins University SOM; Principal Investigator: Kevin Gerold, DOJD, Johns Hopkins University SOM; Study Director: Julie Caffrey, DO, Johns Hopkins University SOM

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 16, 2017
• Primary Completion (ACTUAL): March 28, 2018
• Study Completion (ACTUAL): April 21, 2018

Study Registration Dates

• First Submitted: June 12, 2017
• First Submitted That Met QC Criteria: October 3, 2017
• First Posted (ACTUAL): October 9, 2017

Study Record Updates

• Last Update Posted (ACTUAL): March 12, 2019
• Last Update Submitted That Met QC Criteria: February 18, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: opioid; ketamine
• Additional Relevant MeSH Terms: Mental Disorders; Pain; Neurologic Manifestations; Trauma and Stressor Related Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Acute Pain; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Ketamine; Fentanyl
• Other Study ID Numbers: IRB00089761; NTI-NTRR15-13 (OTHER_GRANT: National Trauma Institute; Departement of Defense)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Plan not operationalized as yet.
• IPD Sharing Time Frame: Data will become available by 1 year after final data publication and remain available for indefinitely.
• IPD Sharing Access Criteria: Written request from faculty investigator to PI or Study Director specifying planned safety & monitoring plan and data analytic aims and hypotheses
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

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