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Trial record 44 of 68 for:    Recruiting, Not yet recruiting, Available Studies | "Thoracic Injuries"

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

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ClinicalTrials.gov Identifier: NCT02432456
Recruitment Status : Recruiting
First Posted : May 4, 2015
Last Update Posted : October 26, 2017
Sponsor:
Information provided by (Responsible Party):
Nathan Kugler, Medical College of Wisconsin

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.

Condition or disease Intervention/treatment Phase
Wounds and Injuries Rib Fractures Drug: Ketamine Drug: Placebo Procedure: Intercostal Nerve Block Drug: Acetaminophen Drug: Ibuprofen Drug: Pantoprazole Drug: Methocarbamol Drug: Opioid Phase 4

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. This trial will focus on adult blunt trauma patients who have associated rib fractures. The focus on adult rib fracture patients stems from an injury pattern in which there is a high incidence of prolonged opiate utilization and development of chronic pain. Elderly rib fracture patients are certainly of interest and this trial will evaluate the benefits of ketamine infusions in this population 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.

A total of 60 patients will be enrolled into the adult arm of the trial with an additional 72 patients enrolled into the elderly arm. 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 : Interventional  (Clinical Trial)
Estimated Enrollment : 132 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Ketamine Infusion Therapy for the Management of Acute Pain in Adult Rib Fracture Patients
Study Start Date : September 2015
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : August 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Ketamine

Arm Intervention/treatment
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.

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

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.

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.

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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. AUCpain [ Time Frame: 6-12 hours post infusion ]
  2. AUCpain [ Time Frame: 2-6 hours post infusion ]
  3. AUCpain [ Time Frame: 24-48 hours post infusion ]
  4. 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.

  5. 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.

  6. Opiate Utilization [ Time Frame: 1st 24 hours post infusion ]
    Standardized to morphine equivalents

  7. Opiate Utilization [ Time Frame: 1st 48 hours post infusion ]
    Standardized to morphine equivalents

  8. 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.

  9. Opiate Side Effect Frequency [ Time Frame: Duration of Infusion (expected average duration of infusion is 4 days) ]
    Nausea, Emesis, Pruritus, Sedation

  10. Regional Anesthesia Utilization [ Time Frame: 1st 48 hours ]
    Epidural, Intercostal Nerve Blocks

  11. 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.

  12. 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.

  13. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02432456


Contacts
Contact: Nathan W Kugler, MD 309-251-9952 nkugler@mcw.edu
Contact: Thomas W Carver, MD 414-805-8622 tcarver@mcw.edu

Locations
United States, Wisconsin
Froedtert Memorial Lutheran Hospital Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Nathan W Kugler, MD    414-805-2955    nkugler@mcw.edu   
Contact: Thomas W Carver, MD    414-805-8622    tcarver@mcw.edu   
Sponsors and Collaborators
Medical College of Wisconsin
Investigators
Principal Investigator: Thomas W Carver, MD Medical College of Wisconsin

Responsible Party: Nathan Kugler, Lead Research Resident, Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT02432456     History of Changes
Other Study ID Numbers: PRO00024679
First Posted: May 4, 2015    Key Record Dates
Last Update Posted: October 26, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Thoracic Injuries
Fractures, Bone
Acute Pain
Wounds and Injuries
Rib Fractures
Pain
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Analgesics, Opioid
Ketamine
Acetaminophen
Ibuprofen
Methocarbamol
Pantoprazole
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Analgesics, Non-Narcotic