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

Ketamine

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).

Intervention / Treatment

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.
  • Ketamine (DRUG)
    Information included in arm descriptions
  • Fentanyl (DRUG)
    Information included in arm descriptions

Condition or Disease

  • Acute Pain
  • Wound Care
  • Posttraumatic Stress Disorder

Phase

  • Phase 4

    • Study Design

    Study type: INTERVENTIONAL
    Status: Terminated
    Study results: No Results Available
    Age: 18 Years to 70 Years
    Enrollment: 4 (ACTUAL)
    Funded by: Other|U.S. Fed
    Allocation: Randomized
    Primary Purpose: Treatment

    Masking

    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).

    QUADRUPLE:
    • Participant
    • Care Provider
    • Investigator
    • Outcomes Assessor

    Clinical Trial Dates

    Start date: Dec 16, 2017 ACTUAL
    Primary Completion: Mar 28, 2018 ACTUAL
    Completion Date: Apr 21, 2018 ACTUAL
    Study First Posted: Oct 09, 2017 ACTUAL
    Results First Posted: Mar 12, 2019 ACTUAL
    Last Updated: Feb 18, 2019

    Sponsors / Collaborators

    Lead Sponsor: Johns Hopkins University
    Lead sponsor is responsible party
    Responsible Party: N/A

    Location

    Baltimore, Maryland, USA

    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.

    Participant Groups

    • 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.

    • 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.

    Eligibility Criteria

    Sex: All
    Minimum Age: 18
    Maximum Age: 70
    Age Groups: Adult / Older Adult
    Healthy Volunteers: Yes

    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) \ * 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)

    Primary Outcomes

    • Average Pain across 14 sessions between the 2 groups and related outcome measures up to 40 days following study enrollment.

    • Trajectory of average pain within session

    • Trajectory of average pain across 7 day study protocol

    • 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 Outcomes

    • 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.

    • 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.

    More Details

    NCT Number: NCT03305055
    Other IDs: IRB00089761
    Study URL: https://clinicaltrials.gov/study/NCT03305055
    Last updated: Sep 29, 2023