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

• Sponsor: Johns Hopkins University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03305055
• Collaborator: United States Department of Defense (U.S. Fed), Congressionally Directed Medical Research Programs (U.S. Fed)
• Enrollment: 4
• Location: 1
• Arms: 2
• Actual Duration (Months): 4.1
• Patients Per Site Per Month: 1

Study Details

Study Description

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

1. depression.

Study Design

• Study Type: Interventional
• 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.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: Dec 16, 2017
• Actual Primary Completion Date: Mar 28, 2018
• Actual Study Completion Date: Apr 21, 2018

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures

1. 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.

2. Trajectory of Mean Wound Care Session Pain Within Sessions [7-days, within session]

   Trajectory of average pain within session

3. Trajectory of Mean Wound Care Session Pain Across Sessions [7-Days across sessions]

   Trajectory of average pain across 7 day study protocol

4. 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

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 17, 2017

More Information

Publications

None provided.

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT03305055
• Other Study ID Numbers: IRB00089761; NTI-NTRR15-13
• First Posted: Oct 9, 2017
• Last Update Posted: Mar 12, 2019
• Last Verified: Feb 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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: Acute Pain; Stress Disorders, Post-Traumatic; Fentanyl; Ketamine

Study Results

Participant Flow

Arm/Group Title	Fentanyl Plus Ketamine	Fentanyl Plus Saline
Arm/Group Description	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. ketamine: Information included in arm descriptions Fentanyl: Information included in arm descriptions	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. Fentanyl: Information included in arm descriptions
Period Title: Overall Study
STARTED	2	2
COMPLETED	1	0
NOT COMPLETED	1	2

Baseline Characteristics

Arm/Group Title	Fentanyl Plus Ketamine	Fentanyl Plus Saline	Total
Arm/Group Description	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. ketamine: Information included in arm descriptions Fentanyl: Information included in arm descriptions	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. Fentanyl: Information included in arm descriptions	Total of all reporting groups
Overall Participants	2	2	4
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44 (35.4)	37 (15.6)	40.5 (22.7)
Sex: Female, Male (Count of Participants)
Female	1 50%	0 0%	1 25%
Male	1 50%	2 100%	3 75%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	2 100%	2 100%	4 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	2 100%	2 100%	4 100%

Outcome Measures

1. Primary Outcome

Title	Mean Wound Care Pain
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Fentanyl Plus Ketamine	Fentanyl Plus Saline
Arm/Group Description	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. ketamine: Information included in arm descriptions Fentanyl: Information included in arm descriptions	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. Fentanyl: Information included in arm descriptions
Measure Participants	0	0

2. Primary Outcome

Title	Trajectory of Mean Wound Care Session Pain Within Sessions
Description	Trajectory of average pain within session
Time Frame	7-days, within session

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Fentanyl Plus Ketamine	Fentanyl Plus Saline
Arm/Group Description	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. ketamine: Information included in arm descriptions Fentanyl: Information included in arm descriptions	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. Fentanyl: Information included in arm descriptions
Measure Participants	0	0

3. Primary Outcome

Title	Trajectory of Mean Wound Care Session Pain Across Sessions
Description	Trajectory of average pain across 7 day study protocol
Time Frame	7-Days across sessions

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Fentanyl Plus Ketamine	Fentanyl Plus Saline
Arm/Group Description	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. ketamine: Information included in arm descriptions Fentanyl: Information included in arm descriptions	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. Fentanyl: Information included in arm descriptions
Measure Participants	0	0

4. Primary Outcome

Title	Opiate Sparing Effect
Description	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

Outcome Measure Data

Analysis Population Description

Data was not collected for this outcome measure.

Arm/Group Title	Fentanyl Plus Ketamine	Fentanyl Plus Saline
Arm/Group Description	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. ketamine: Information included in arm descriptions Fentanyl: Information included in arm descriptions	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. Fentanyl: Information included in arm descriptions
Measure Participants	0	0

5. Secondary Outcome

Title	Post Traumatic Stress Disorder (PTSD) Symptoms as Assessed by Davidson Trauma Scale
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Fentanyl Plus Ketamine	Fentanyl Plus Saline
Arm/Group Description	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. ketamine: Information included in arm descriptions Fentanyl: Information included in arm descriptions	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. Fentanyl: Information included in arm descriptions
Measure Participants	0	0

6. Secondary Outcome

Title	Depression Symptoms as Assessed by the Patient Health Questionnaire
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Fentanyl Plus Ketamine	Fentanyl Plus Saline
Arm/Group Description	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. ketamine: Information included in arm descriptions Fentanyl: Information included in arm descriptions	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. Fentanyl: Information included in arm descriptions
Measure Participants	0	0

Adverse Events

Time Frame	End of study (approximately 37 days)
Arm/Group Title	Fentanyl Plus Ketamine		Fentanyl Plus Saline
Arm/Group Description	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. ketamine: Information included in arm descriptions Fentanyl: Information included in arm descriptions		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. Fentanyl: Information included in arm descriptions
All Cause Mortality
	Fentanyl Plus Ketamine		Fentanyl Plus Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/2 (0%)
Serious Adverse Events
	Fentanyl Plus Ketamine		Fentanyl Plus Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Fentanyl Plus Ketamine		Fentanyl Plus Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/2 (50%)		1/2 (50%)
Skin and subcutaneous tissue disorders
Pain at wound site	1/2 (50%)	1	1/2 (50%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.