Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Ketamine Infusion Therapy for the Management of Acute Pain in Adult Rib Fracture Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02432456
Recruitment Status : Completed
First Posted : May 4, 2015
Results First Posted : February 5, 2020
Last Update Posted : February 5, 2020
Sponsor:
Information provided by (Responsible Party):
Nathan Kugler, Medical College of Wisconsin

Tracking Information
First Submitted Date  ICMJE April 20, 2015
First Posted Date  ICMJE May 4, 2015
Results First Submitted Date  ICMJE December 15, 2019
Results First Posted Date  ICMJE February 5, 2020
Last Update Posted Date February 5, 2020
Study Start Date  ICMJE September 2015
Actual Primary Completion Date August 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 27, 2020)
Visual Analog Numeric Pain Score [ Time Frame: 12-24 hours post infusion ]
Visual Analog Numeric Pain scores are reported as a single numeric score between 0 and 10. The more severe the pain the higher the number with 10 representing the most severe pain imaginable.
Original Primary Outcome Measures  ICMJE
 (submitted: April 28, 2015)
AUCpain [ Time Frame: 12-24 hours post infusion ]
Primary outcome will be the area under curve for the pain trajectory (AUCpain) during the 12 - 24 hours after initiation of pain treatment
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 27, 2020)
  • Visual Analog Numeric Pain Score [ Time Frame: 24-48 hours post infusion ]
    Visual Analog Numeric Pain scores are reported as a single numeric score between 0 and 10. The more severe the pain the higher the number with 10 representing the most severe pain imaginable.
  • Oral Morphine Equivalent (Narcotic Usage) [ Time Frame: 12-24 hours post infusion ]
    This is an analysis of the narcotic utilization during the study. Oral Morphine Equivalents is a means of standardizing narcotic utilization given a multitude of different medications are utilized. Medications are standardized to units (milligrams) or oral morphine for a standardized comparison.
  • Oral Morphine Equivalent (Narcotic Usage) [ Time Frame: 24-48 hours post infusion ]
    This is an analysis of the narcotic utilization during the study. Oral Morphine Equivalents is a means of standardizing narcotic utilization given a multitude of different medications are utilized. Medications are standardized to units (milligrams) or oral morphine for a standardized comparison.
  • Length of Stay [ Time Frame: Total Index Hospitalization up to 365 days ]
    Total hospital length of stay in days up to 365 days.
  • Regional Anesthesia Utilization [ Time Frame: Total Index Hospitalization up to 365 days ]
    This is a measure of the Epidural Placement rates. Epidural placement was binary as in patient received or did not receive an epidural infusion catheter for supplemental pain management.
  • Respiratory Failure [ Time Frame: Total Index Hospitalization up to 365 days ]
    Respiratory failure within this trial was defined by the need for unanticipated intubation and/or transfer to ICU for respiratory support.
  • Hallucination [ Time Frame: Total Index Hospitalization up to 365 days ]
    Hallucinations were documented and confirmed by the treating medical team.
  • Oral Morphine Equivalent (Narcotic Usage) in Severely Injured [ Time Frame: Total Index Hospitalization up to 365 days ]
    This is an analysis of the narcotic utilization during the study. Oral Morphine Equivalents is a means of standardizing narcotic utilization given a multitude of different medications are utilized. Medications are standardized to units (milligrams) or oral morphine for a standardized comparison.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 28, 2015)
  • AUCpain [ Time Frame: 6-12 hours post infusion ]
  • AUCpain [ Time Frame: 2-6 hours post infusion ]
  • AUCpain [ Time Frame: 24-48 hours post infusion ]
  • ICU Length of Stay [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 5-7 days. ]
    Participants will be followed from time of admission to time of discharge. The average hospital length of stay is expected to be 5-7 days.
  • Length of Stay [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 5-7 days. ]
    Participants will be followed from time of admission to time of discharge. The average hospital length of stay is expected to be 5-7 days.
  • Opiate Utilization [ Time Frame: 1st 24 hours post infusion ]
    Standardized to morphine equivalents
  • Opiate Utilization [ Time Frame: 1st 48 hours post infusion ]
    Standardized to morphine equivalents
  • Opiate Utilization [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 5-7 days. ]
    Participants will be followed from time of admission to time of discharge. The average hospital length of stay is expected to be 5-7 days.
  • Opiate Side Effect Frequency [ Time Frame: Duration of Infusion (expected average duration of infusion is 4 days) ]
    Nausea, Emesis, Pruritus, Sedation
  • Regional Anesthesia Utilization [ Time Frame: 1st 48 hours ]
    Epidural, Intercostal Nerve Blocks
  • Regional Anesthesia Utilization [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 5-7 days. ]
    Epidural, Intercostal Nerve Blocks. Participants will be followed from time of admission to time of discharge. The average hospital length of stay is expected to be 5-7 days.
  • Rib Fracture Complication Frequency [ Time Frame: Admission up to 3 months post-discharge ]
    Including Pneumonia, Oxygen Dependency, Need for Non-Invasive Ventilation, Intubation. Participants will be followed from time of admission to time of discharge. The average hospital length of stay is expected to be 5-7 days.
  • Development of Chronic Pain [ Time Frame: Admission up through 3-4 months post discharge ]
    Chronic pain will be defined based on responses to the brief pain index - short form evaluation completed by patients.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ketamine Infusion Therapy for the Management of Acute Pain in Adult Rib Fracture Patients
Official Title  ICMJE Ketamine Infusion Therapy for the Management of Acute Pain in Adult Rib Fracture Patients
Brief Summary This study will evaluate the effectiveness of ketamine infusions in the management of acute pain resulting from broken ribs suffered following a blunt trauma. Half of patients will receive the institutional standard of care and a placebo infusion (no active medication). The other half of patients will receive the institutional standard of care and a ketamine infusion. All subjects and staff will be blinded as to whether they are receiving placebo or ketamine.
Detailed Description

A prospective randomized, double blinded trial of ketamine use in adult and elderly blunt trauma patients with associated rib fractures admitted to the trauma service will be conducted. Examples of blunt mechanisms include assault, falls, motor vehicle collisions, motorcycle crashes, motor vehicle pedestrian collisions, crush injuries, and bicycle accidents. The experimental arm of the trial will receive ketamine infusion therapy while the control arm receives saline placebo infusions at an equivalent rate. All patients will be managed with adjunct therapy including opiates in accordance with the institutional thoracic trauma protocols. Two separate trials based on patient age are included in this study. Elderly rib fracture patients are certainly of interest but will be evaluated as a distinct entity given the discrete differences in the complications of rib fractures and the goals of therapy.

All blunt trauma patients with associated rib fractures will be screened. All patients will be enrolled into the institutional standard thoracic trauma pathway. All individuals will undergo Intercostal Nerve Block (ICNB) in the Emergency Department or on admission to the Intensive Care Unit. In addition to scheduled medications per institutional thoracic trauma protocols, all patients will receive adjunct opiate therapy. Patients will be screened by the clinical and pharmacy staff following the diagnosis of rib fractures for eligibility. Patients enrolled into the trial will be randomized into either the experimental or control arm of the trial. The Investigational Drug Services (IDS) department will randomize all enrollees and handle administration of all trial drugs. The infusate will be mixed by the IDS department and all bags will be labeled "Ketamine / Placebo." The IDS department will have unique bag identifiers, which will allow them to identify which bags have active ketamine and which are placebo in case of emergency.

Patients will be randomized in a 1:1 fashion for experimental and control arms. Those enrolled in the experimental arm will receive early ketamine infusion therapy at a fixed infusion rate. For those enrolled in the adult trial the infusion rate will be 2.5 mcg/kg/min while those in the elderly trial will receive infusions at 2.0 mcg/kg/min. All ketamine infusions will be calculated based on ideal body weight (IBW), unless actual body weight is less than ideal. IBW will be calculated for males as 50kg + 2.3*(number of inches above 5 feet) and for women as 45.5kg + 2.3*(number of inches over 5 feet). Patients randomized to the control arm will receive placebo saline solution at an equivalent rate. Time zero will be defined as the time at which the "ketamine / placebo" infusion is begun. For inclusion in the trial, initiation of ketamine / placebo infusions must take place within 6 hours of presentation to Froedtert Memorial Lutheran Hospital (FMLH). Ketamine infusion therapy will be continued for 48 hours. At 6-8 hours post-ICNB all subjects will be assessed for need for repeat ICNB. Need for repeat ICNB will be defined by a thoracic specific numeric pain score greater than seven. Between eight and ten hours post-ketamine infusion initiation, subjects who have thoracic specific pain scores above seven will be evaluated for epidural placement by the Regional Anesthesia and Acute Pain Service.

A subject will be allowed to remove himself/herself from the trial or be un-blinded should he/she, pharmacy, anesthesia, and/or surgical staff deem it medically necessary. Medical necessity would be determined by inability to treat the patient appropriately without knowledge of trial assignment; otherwise the assumption of treating staff will be all patients have received ketamine. All adverse events will be recorded and if necessary subjects will be un-blinded in the event of a serious adverse event. The trauma and anesthesia teams along with the inpatient clinical pharmacists will monitor all trial patients for any adverse event trends. Patients will be followed through the time of discharge.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Wounds and Injuries
  • Rib Fractures
Intervention  ICMJE
  • Drug: Ketamine
    All individuals randomized to the experimental arm of the trial will receive early ketamine therapy (within 6 hours of admission) at a rate of 0.15 mg/kg/hr dosed based on ideal body weight. Individuals in the control arm will receive our standard of care for thoracic trauma patients, however, they will receive an additional placebo infusion of normal saline.
  • Drug: Placebo
    Individuals enrolled into the control arm of the trial will receive a normal saline placebo infusion at a rate equivalent to the dosage of ketamine in the experimental arm.
    Other Name: NaCl Placebo Solution
  • Procedure: Intercostal Nerve Block
    All individuals enrolled into the trial will undergo an Intercostal Nerve Blockade as a part of the institutional standard of care for rib fractures. This procedure will be performed according to current standard protocols in the Emergency Department or on admission.
    Other Name: Rib Block
  • Drug: Acetaminophen
    All patients admitted to the hospital will be placed on scheduled acetaminophen 1000mg PO q 6 hours unless signs of liver disease/impairment or creatinine clearance < 35ml/min at which point dosage would be reduced to 650mg q 8 hours. Individuals unable to take oral medications would be placed on intravenous acetaminophen.
    Other Name: Tylenol
  • Drug: Ibuprofen
    All patients will be placed on scheduled Ibuprofen or an equivalent NSAID at dosage of 600mg every 6 hours. Patients must have a Glomerular Filtration Rate > 60 ml/min with no contraindications to NSAID therapy (e.g. Aspirin use, allergy/sensitivity, concurrent ACE inhibitor use, other nephrotoxins, etc)
    Other Name: Advil, Motrin
  • Drug: Pantoprazole
    All individuals on scheduled Non-Steroidal Anti-Inflammatory Drug (NSAID) therapy will receive scheduled pantoprazole at 40mg daily. Individuals unable to take medications orally will be placed on intravenous therapy. Individuals with previous reaction or intolerance to pantoprazole will be placed on an equivalent proton pump inhibitor.
    Other Name: Protonix
  • Drug: Methocarbamol
    All individuals enrolled in the trial will be placed on scheduled methocarbamol 500 mg orally every 6 hours while admitted. Individuals with previous intolerance to methocarbamol will be placed on a pharmacy directed equivalent.
    Other Name: Robaxin
  • Drug: Opioid
    All individuals will receive as needed opiate therapy as an adjunct to the scheduled medications and "ketamine/placebo" solution. Choice in opiate therapy will be at the discretion of the attending trauma faculty. Dosage and adjustments will be in accordance with the institutional policy on appropriate opiate dosage adjustment.
    Other Name: opiate, narcotic
Study Arms  ICMJE
  • Placebo Comparator: Placebo Infusion

    Subjects in this arm will receive the institutional standard of care for rib fractures along with a placebo (NaCl) infusion.

    All patients will undergo Intercostal Nerve Blockade with administration of scheduled medications including acetaminophen, ibuprofen, pantoprazole, and methocarbamol. All subjects will receive adjunct opioids.

    Interventions:
    • Drug: Placebo
    • Procedure: Intercostal Nerve Block
    • Drug: Acetaminophen
    • Drug: Ibuprofen
    • Drug: Pantoprazole
    • Drug: Methocarbamol
    • Drug: Opioid
  • Experimental: Ketamine Infusion

    Subjects in this arm will receive the institutional standard of care for rib fractures along with a ketamine infusion.

    All patients will undergo Intercostal Nerve Blockade with administration of scheduled medications including acetaminophen, ibuprofen, pantoprazole, and methocarbamol. All subjects will receive adjunct opioids.

    Interventions:
    • Drug: Ketamine
    • Procedure: Intercostal Nerve Block
    • Drug: Acetaminophen
    • Drug: Ibuprofen
    • Drug: Pantoprazole
    • Drug: Methocarbamol
    • Drug: Opioid
Publications * Carver TW, Kugler NW, Juul J, Peppard WJ, Drescher KM, Somberg LB, Szabo A, Yin Z, Paul JS. Ketamine infusion for pain control in adult patients with multiple rib fractures: Results of a randomized control trial. J Trauma Acute Care Surg. 2019 Feb;86(2):181-188. doi: 10.1097/TA.0000000000002103.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 27, 2020)
153
Original Estimated Enrollment  ICMJE
 (submitted: April 28, 2015)
60
Actual Study Completion Date  ICMJE August 2018
Actual Primary Completion Date August 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. age greater than 18 years
  2. rib fractures following recent trauma with admission to Froedtert Memorial Lutheran Hospital

Exclusion Criteria:

  1. history of adverse reaction / intolerance to ketamine therapy
  2. elevated intracranial pressure
  3. ischemic heart disease defined as active acute coronary syndrome
  4. severe, poorly controlled hypertension (Systolic Blood Pressure > 200 mmHg or Diastolic Blood Pressure > 100 mmHg)
  5. current opiate agonist/antagonist therapy
  6. concurrent use of monoamine oxidase inhibitors (MAOIs)
  7. chronic pain or opioid tolerance defined as > 3 weeks of >30mg oral morphine equivalents per day
  8. current substance abuse with opiates (prescription and/or heroin) or ketamine
  9. Glasgow Coma Scale <13
  10. Intubation on arrival or need for urgent intubation on arrival
  11. inability to delineate pain and/or appropriately communicate with staff
  12. history of psychosis
  13. three or more psychotropic medications
  14. active delirium
  15. glaucoma
  16. pregnancy
  17. prisoners
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02432456
Other Study ID Numbers  ICMJE PRO00024679
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Nathan Kugler, Medical College of Wisconsin
Study Sponsor  ICMJE Medical College of Wisconsin
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Thomas W Carver, MD Medical College of Wisconsin
PRS Account Medical College of Wisconsin
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP