Acute Pain, Posttraumatic Stress Disorder, Wound Care
Conditions
Keywords
opioid, 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).
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.
Interventions
DRUGketamine
Information included in arm descriptions
DRUGFentanyl
Information included in arm descriptions
Sponsors
United States Department of Defense
Congressionally Directed Medical Research Programs
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, 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).
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Trajectory of Mean Wound Care Session Pain Within Sessions | 7-days, within session | Trajectory of average pain within session |
| Trajectory of Mean Wound Care Session Pain Across Sessions | 7-Days across sessions | Trajectory of average pain across 7 day study protocol |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
ketamine: Information included in arm descriptions
Fentanyl: Information included in arm descriptions | 2 |
| 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.
Fentanyl: Information included in arm descriptions | 2 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Fentanyl Plus Ketamine | Fentanyl Plus Saline | Total |
|---|---|---|---|
| Age, Continuous | 44 years STANDARD_DEVIATION 35.4 | 37 years STANDARD_DEVIATION 15.6 | 40.5 years STANDARD_DEVIATION 22.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 2 participants | 2 participants | 4 participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 2 |
| other Total, other adverse events | 1 / 2 | 1 / 2 |
| serious Total, serious adverse events | 0 / 2 | 0 / 2 |
Outcome results
Primary
Mean Wound Care Pain
Average Pain across 14 sessions between the 2 groups and related outcome measures up to 40 days following study enrollment.
Time frame: Up to 40 days
Population: Data was not collected for the minimum threshold \[per the statistical analysis plan\] of 6-11 consecutive wound care sessions to assess this outcome measure
Primary
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).
Time frame: 37 days
Population: Data was not collected for this outcome measure.
Primary
Trajectory of Mean Wound Care Session Pain Across Sessions
Trajectory of average pain across 7 day study protocol
Time frame: 7-Days across sessions
Population: Data was not collected for the minimum threshold \[per the statistical analysis plan\] of 6-11 consecutive wound care sessions to assess this outcome measure
Primary
Trajectory of Mean Wound Care Session Pain Within Sessions
Trajectory of average pain within session
Time frame: 7-days, within session
Population: Data was not collected for the minimum threshold \[per the statistical analysis plan\] of 6-11 consecutive wound care sessions to assess this outcome measure
Secondary
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.
Time frame: 37 days
Population: Data was not collected for the minimum threshold \[per the statistical analysis plan\] of 6-11 consecutive wound care sessions to assess this outcome measure
Secondary
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.
Time frame: 37 days
Population: Data was not collected for the minimum threshold \[per the statistical analysis plan\] of 6-11 consecutive wound care sessions to assess this outcome measure