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

NCT03305055 | Terminated Phase 4 Results DMC FDA Drug

• 2 other identifiers: IRB00089761NTI-NTRR15-13
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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).

Conditions

Acute Pain; Wound Care; Posttraumatic Stress Disorder

Keywords

opioid; ketamine

Outcome Measures

Primary Outcomes (4)

• Mean Wound Care Pain

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

  Up to 40 days

• Trajectory of Mean Wound Care Session Pain Within Sessions

  Trajectory of average pain within session

  7-days, within session

• Trajectory of Mean Wound Care Session Pain Across Sessions

  Trajectory of average pain across 7 day study protocol

  7-Days across sessions

• 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).

  37 days

Secondary Outcomes (2)

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

  37 days

• Depression Symptoms as Assessed by the Patient Health Questionnaire

  37 days

Study Arms (2)

Fentanyl Plus Ketamine

EXPERIMENTAL

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; Drug: Fentanyl

Fentanyl Plus Saline

ACTIVE COMPARATOR

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

Interventions

ketamine DRUG

Information included in arm descriptions

Also known as: STUDY DRUG GROUP (Fentanyl plus Ketamine)

Fentanyl Plus Ketamine

Fentanyl DRUG

Information included in arm descriptions

Also known as: USUAL CARE GROUP (Fentanyl plus saline/placebo)

Fentanyl Plus Ketamine; Fentanyl Plus Saline

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Johns Hopkins University: lead
• United States Department of Defense: collaborator
• Congressionally Directed Medical Research Programs: collaborator

Study Sites (1)

Johns Hopkins Burn Center

Baltimore, Maryland, 21224, United States

Location

MeSH Terms

Conditions

Acute Pain; Stress Disorders, Post-Traumatic

Interventions

Ketamine; Fentanyl; Sodium Chloride

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: James A. Fauerbach
• Organization: Johns Hopkins University

jfauerb1@jhmi.edu

410-550-0890

Study Officials

• James A Fauerbach, PhD

  Johns Hopkins University SOM

  PRINCIPAL INVESTIGATOR

• Kevin Gerold, DOJD

  Johns Hopkins University SOM

  PRINCIPAL INVESTIGATOR

• Julie Caffrey, DO

  Johns Hopkins University SOM

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: June 12, 2017
• First Posted: October 9, 2017
• Study Start: December 16, 2017
• Primary Completion: March 28, 2018
• Study Completion: April 21, 2018
• Last Updated: March 12, 2019
• Results First Posted: March 12, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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

Locations

US (1)