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

Phase 4

Terminated

Conditions: Acute Pain
Wound Care
Posttraumatic Stress Disorder

Interventions: Drug: ketamine
Drug: Fentanyl

Registration Number: NCT03305055

Lead Sponsor: 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).

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 4

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fentanyl Plus Ketamine	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.
Fentanyl Plus Ketamine	Fentanyl	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.
Fentanyl Plus Saline	Fentanyl	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.

Primary Outcome Measures

Name	Time	Method
Trajectory of Mean Wound Care Session Pain Across Sessions	7-Days across sessions	Trajectory of average pain across 7 day study protocol
Trajectory of Mean Wound Care Session Pain Within Sessions	7-days, within session	Trajectory of average pain within session
Mean Wound Care Pain	Up to 40 days	Average Pain across 14 sessions between the 2 groups and related outcome measures up to 40 days following study enrollment.
Opiate Sparing Effect	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

Name	Time	Method
Post Traumatic Stress Disorder (PTSD) Symptoms as Assessed by Davidson Trauma Scale	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.
Depression Symptoms as Assessed by the Patient Health Questionnaire	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.