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Analgosedative adjuncT keTAmine Infusion iN Mechanically vENTilated ICU Patients (ATTAINMENT)

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ClinicalTrials.gov Identifier: NCT04075006
Recruitment Status : Recruiting
First Posted : August 30, 2019
Last Update Posted : September 18, 2019
Sponsor:
Information provided by (Responsible Party):
Mohammed Bawazeer, King Faisal Specialist Hospital & Research Center

Brief Summary:
The purpose of this study is to investigate the efficacy and safety of a low dose ketamine infusion used in combination of standard of care in critically ill patients to test whether ketamine can help to shorten the time of being in breathing tube and ventilator compared to the standard of care alone.

Condition or disease Intervention/treatment Phase
Critical Illness Sedation Mechanical Ventilation Drug: Ketamine Phase 3

Detailed Description:

Ketamine is used to produce sedation and relieve pain to minimize discomfort while a breathing tube placed in trachea (windpipe) and a machine (ventilator) used in the ICU. Several publications have shown that a low-dose ketamine in combination to opioids has been used to relieve acute pain after surgery. Ketamine has a favorable characteristics including bronchodilation, increase in blood pressure, does not cause constipation , maintain respiratory reflexes (respiratory spontaneous responses) make it an especially viable alternative for patients with unstable respiratory and hemodynamic function. However, the majority of these trials are conducted in a surgical ICU setting, retrospective in nature or randomized controlled clinical trials focusing on comparison of ketamine to placebo or two study drugs (e.g. ketamine versus opioid), despite the fact that most ICU patients are sedated with a combination of drugs. Moreover, the majority of those trials has a limited focus on patient-centered outcomes, as the primary outcome.

The aim of this study is to assess weather ketamine can help to shorten the time of being in breathing tube and ventilator (duration of mechanical ventilation). This is a prospective, randomized, active controlled, open-label pilot study to assess the efficacy and safety of Analgo-sedative adjuncT keTAmine Infusion iN Mechanically vENTilated ICU patients (ATTAINMENT trial). The study hypothesis is that low dose ketamine infusion will reduce the duration of mechanical ventilation with an acceptable safety profile compared to standard of care. The study will include adult ICU patients (> 14 years old) admitted to KFSHRC ICUs within the previous 24 hours, placed on the ventilator, expected to need breathing tube for longer than 24 hours and placed on KFSHRC sedation and pain protocol. Patients will be separated to 2 groups: The intervention group: will receive a low dose ketamine infusion used in combination of standard of care. Ketamine will be given as intravenous infusion at a fixed infusion rate 0.12 mg/kg/hr (2 µg/kg/min) in 1st 24hr followed by 0.06 mg/kg/hr (1 µg/kg/min) in 2nd 24hr. The control group which will receive standard of care in the ICU including propofol and / or fentanyl and/or midazolam according to KFSHRC ICU sedation and analgesia protocol as chosen by the treating clinician.The randomization process is computer-generated using block randomization with a size of 8 patients in each block.

The number of the subjects to be enrolled in this study is 80 and duration of the subject's participation is 48hrs. Patients will be assessed for duration of mechanical ventilation as a primary outcome.

Study medication (i.e. ketamine) will be administered until one the following occurs:

  1. Patient has received ketamine for 48 hours (intended duration if the study), or
  2. If ICU team deemed excessive sedation persisted after holding or decreasing the sedating medication and patient not on target sedation score called RASS,
  3. Patient died or goal of care changed to comfort care
  4. Patient extubated and sedation weaned off ,
  5. an adverse event potentially attributable to the study drug is experienced by a patient that is deemed, in the opinion of the investigative team to warrant discontinuation of therapy such as fast heart beat persist >150 beat per min for more than 3 hours, high systolic blood pressure persist > 180 for more than 3 hours, severe agitation and pulling off breathing tube or lines, and aggressive behavior to the nursing staff.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Adjunct Low Dose Ketamine Infusion Versus Standard of Care in Mechanically Ventilated Critically Ill Patients at a Tertiary Saudi Hospital: Randomized, Prospective, Pilot Trial
Actual Study Start Date : August 28, 2019
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Ketamine

Arm Intervention/treatment
Experimental: Ketamine Group
adjunct low dose continuous infusion ketamine in addition to the standard of care. Ketamine will be given at a fixed infusion rate of 0.12 mg/kg/hr (2 µg/kg/min) in the first 24 hours followed by 0.06 mg/kg/hr (1 µg/kg/min) in the second 24 hours, then discontinued
Drug: Ketamine
standard of care plus Ketamine infusion at a fixed rate of 0.12 mg/kg/hr (2 µg/kg/min) in the first 24 hours followed by 0.06 mg/kg/hr (1 µg/kg/min) in the second 24 hours, then discontinued

No Intervention: Control Group
Standard of care in the ICU including propofol and / or fentanyl and/or midazolam according to KFSHRC sedation and analgesia protocol.



Primary Outcome Measures :
  1. Duration of Mechanical Ventilation [ Time Frame: From Intubation to extubation date and off Mechanical Ventilation or until ICU discharge, death, or 28 days post randomization whichever occurs first. ]
    To assess whether ketamine can help to shorten the time of being in breathing tube and ventilator (duration of mechanical ventilation )


Secondary Outcome Measures :
  1. Cumulative Sedation Dosages [ Time Frame: First 48 hours after randomization ]
    To compare the cumulative dose of pain and sedative medications.

  2. Dexmedetomidine use [ Time Frame: First 48 hours after randomization ]
    To compare the number of patients started on dexmedetomidine.

  3. Richmond Agitation Sedation Score (RASS) [ Time Frame: First 48 hours after randomization ]
    To compare The number of patients are in RASS score goal.

  4. Pain score [ Time Frame: First 48 hours after randomization ]

    To compare The number of patients are in pain score goal. We will use the KFSHRC pain scale being used in our ICU.

    For Adult communicative patients, we will use a scale from 0-10. The "0" indicates "No pain" and "10" indicates "severe pain". Values between 1-3 indicate mild pain, values between 4-6 indicate moderate pain while values between 7-10 indicate severe pain.

    For non-communicative patients, A scale is composed of five categories: Physiology, Facial expressions, Activity (movement), Guarding And Respiratory, will be used. Each Category has a scale 0-2, then the total score is calculated and should be between 0-10. Values between 0-2 indicate no pain, values 3-6 indicate moderate pain while values between 7-10 indicate severe pain.


  5. Vasopressor Medication Dosages [ Time Frame: First 48 hours after randomization. ]
    To compare vasopressor requirement.

  6. Hospital Length of Stay (LOS) [ Time Frame: Throughout study completion (1 year) ]
    To compare hospital LOS

  7. ICU Length of stay (LOS) [ Time Frame: Throughout study completion (1 year) ]
    To compare ICU LOS

  8. Tracheostomy [ Time Frame: 28 days after randomization ]
    Tracheostomy rate

  9. Unplanned extubation [ Time Frame: 28 days after randomization ]
    Rate of unplanned extubation

  10. Re-intubation rate [ Time Frame: 28 days after randomization ]
    Rate of unplanned and unexpected re-intubation


Other Outcome Measures:
  1. Incidence of Delirium [ Time Frame: 48 hours after randomization ]
    Rate of positive Confusion Assessment Method in Intensive Care Unit (CAM-ICU)

  2. The use of anti-psychotics [ Time Frame: 48 hours after randomization ]
    Rate of using anti-psychotics for confirmed ICU-acquired delirium

  3. Use of Physical restraints [ Time Frame: 48 hours after randomization ]
    Use of physical restraints

  4. Mortality [ Time Frame: 28 days after randomization ]
    Death that occurs during 28 days



Information from the National Library of Medicine

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Ages Eligible for Study:   14 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adult ICU (Medical or surgical) patients (> 14 years old)
  2. Mechanically ventilated within the previous 24 hours and expected to remain intubated for more than 24 hours.
  3. The patient requires ongoing sedative medication
  4. No objection from the ICU attending MD for enrollment

Exclusion Criteria:

  1. Patients with a history of dementia or psychiatric disorders or on any anti-psychotics or anti-depressants medications at home
  2. Pregnancy
  3. Age < 14 years old
  4. Expected to need mechanical ventilation less than 24 hours
  5. Known hypersensitivity to ketamine
  6. Patient on dexmedetomidine as primary sedative agent prior to randomization
  7. Patients with cardiogenic shock, heart failure, myocardial infarction
  8. History of end-stage liver disease.
  9. Proven or suspected primary neurological injury (traumatic brain injury, ischemic stroke, intracranial hemorrhage, spinal cord injury, anoxic brain injury)
  10. Patients with persistent heart rate (HR) > 150 bpm or systolic blood pressure (SBP) >180 mmHg
  11. Patients who assigned as do-not-resuscitate order (DNR) or expected to die within 24 hours
  12. Patients on ECMO
  13. Patients with status epilepticus patients who are receiving the ketamine infusion for refractory status epilepticus
  14. Proven or suspected status asthmaticus

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): NCT04075006


Contacts
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Contact: Mohammed Bawazeer, MD, FRCSC, FACS +966112162919 ext 24731 mbawazeer@kfshrc.edu.sa
Contact: Marwa Amer, PharmD, BCPS, BCCCP +966112162919 ext 24731 mamer@kfshrc.edu.sa

Locations
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Saudi Arabia
King Faisal Specialist Hospital and Research Centre Recruiting
Riyadh, Saudi Arabia, 11211
Contact: Abeer Omar    +966114424528    aomar@kfshrc.edu.sa   
Principal Investigator: Mohammed Bawazeer, MD, FRCSC, FACS         
Principal Investigator: Marwa Amer, PharmD, BCPS, BCCCP         
Sub-Investigator: Khalid Maghrabi, MD, Chairman         
Sub-Investigator: Mohammed Hijazi, MD, Consultant Intensivist         
Sub-Investigator: Kamel Al-Sheikh, MD, Assistant Consultant         
Sub-Investigator: Muhammad Rizwan, MD, Assistant Consultant         
Sub-Investigator: Rashid Amin, PharmD, BCPS, BCCCP         
Sub-Investigator: Edward De Vol, Chairman, Biostat, Epidem         
Sub-Investigator: Mohammad Shaban, MD, Assistant Consultant         
Sponsors and Collaborators
King Faisal Specialist Hospital & Research Center

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Responsible Party: Mohammed Bawazeer, Consultant Intensivist, King Faisal Specialist Hospital & Research Center
ClinicalTrials.gov Identifier: NCT04075006     History of Changes
Other Study ID Numbers: 2191187
SCTR #19063002 ( Other Identifier: Saudi Food and Drug Authority )
First Posted: August 30, 2019    Key Record Dates
Last Update Posted: September 18, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Mohammed Bawazeer, King Faisal Specialist Hospital & Research Center:
Ketamine, standard of care, critically ill, mechanically ventilation, ATTAINMENT, propofol, Fentanyl , midazolam , delirium, vasopressors
Additional relevant MeSH terms:
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Ketamine
Critical Illness
Disease Attributes
Pathologic Processes
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action