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

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ClinicalTrials.gov Identifier: NCT03305055
Recruitment Status : Terminated (Funding withdrawn - slow enrollment)
First Posted : October 9, 2017
Last Update Posted : December 3, 2018
Sponsor:
Collaborators:
United States Department of Defense
Congressionally Directed Medical Research Programs
Information provided by (Responsible Party):
Johns Hopkins University

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Acute Pain Wound Care Posttraumatic Stress Disorder Drug: ketamine Drug: Fentanyl Phase 4

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  (Clinical Trial)
Actual Enrollment : 4 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, placebo-controlled, repeated exposure (twice daily, 7 days), safety and efficacy trial of Usual Care (fentanyl PLUS saline / placebo) versus Usual Care plus Study Drug Augmentation (fentanyl PLUS ketamine) in reducing acute pain severity assessed before, during and after wound care for acute burn injury in the Burn Center of an Academic Medical Center.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Pharmacy receives order from provider and then prepares the study drug in an unmarked, nondescript delivery system ("bag") and the study drug information is entered from the bag into the pump so that delivery that is timed and volume controlled per study protocol. This is hung next to patient, connected and started. Masked personnel include provider (order study drug protocol), nurse (wound care), data assessor (Research Assistant), and consenting participant (patient with acute burn).
Primary Purpose: Treatment
Official Title: Evaluating the Safety, Efficacy and Opiate Sparing Effects of Low-Dose, Slow Infusion Ketamine as a Battlefield Analgesic for Acute Pain in Burn Wounds.
Actual Study Start Date : December 16, 2017
Actual Primary Completion Date : March 28, 2018
Actual Study Completion Date : April 21, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Fentanyl Plus Ketamine

Study drug group

  1. 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,

  2. 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.

  3. 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 Name: STUDY DRUG GROUP (Fentanyl plus Ketamine)

Drug: Fentanyl
Information included in arm descriptions
Other Name: USUAL CARE GROUP (Fentanyl plus saline/placebo)

Active Comparator: Fentanyl Plus Saline

Usual care group

  1. 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, ...

  2. 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.

  3. 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 Name: USUAL CARE GROUP (Fentanyl plus saline/placebo)




Primary Outcome Measures :
  1. Mean Wound Care Pain [ Time Frame: Up to 35 days following study protocol initiation with each participant. ]
    Average Pain across 14 sessions between the 2 groups and related outcome measures up to 40 days following study enrollment.

  2. Trajectory of Mean Wound Care Session Pain (A.; B.) [ Time Frame: A. 7-days, within session; B. 7-Days across sessions (1-14) ]
    A. Trajectory of average pain within session; B. Trajectory of pain averages across sessions 1-14 across 7 day study protocol

  3. Opiate Sparing Effect [ Time Frame: 37 days ]
    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).


Secondary Outcome Measures :
  1. Post Traumatic Stress Disorder (PTSD) symptoms as assessed by Davidson Trauma Scale [ Time Frame: 37 days ]
    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.

  2. Depression symptoms as assessed by the Patient Health Questionnaire [ Time Frame: 37 days ]
    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.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 7 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 (eg potential drug interactions or medical comorbid conditions)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03305055


Locations
United States, Maryland
Johns Hopkins Burn Center
Baltimore, Maryland, United States, 21224
Sponsors and Collaborators
Johns Hopkins University
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

Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT03305055     History of Changes
Other Study ID Numbers: IRB00089761
NTI-NTRR15-13 ( Other Grant/Funding Number: National Trauma Institute; Departement of Defense )
First Posted: October 9, 2017    Key Record Dates
Last Update Posted: December 3, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Plan not operationalized as yet.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: Data will become available by 1 year after final data publication and remain available for indefinitely.
Access Criteria: Written request from faculty investigator to PI or Study Director specifying planned safety & monitoring plan and data analytic aims and hypotheses

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

Keywords provided by Johns Hopkins University:
opioid
ketamine

Additional relevant MeSH terms:
Stress Disorders, Post-Traumatic
Acute Pain
Stress Disorders, Traumatic
Trauma and Stressor Related Disorders
Mental Disorders
Pain
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Ketamine
Fentanyl
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Analgesics, Opioid
Narcotics
Adjuvants, Anesthesia