Analgosedative adjuncT keTAmine Infusion iN Mechanically vENTilated ICU Patients

Critical Illness Clinical Trial

— ATTAINMENT  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04075006
• Other study ID #: 2191187
• Secondary ID: SCTR #19063002IS
• Status: Completed
• Phase: Phase 3
• Start date: August 28, 2019
• Est. completion date: May 6, 2021

Study information

• Verified date: May 2021
• Source: King Faisal Specialist Hospital & Research Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: May 6, 2021
• Est. primary completion date: May 6, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years and older

Eligibility

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

15. Patients with expected targeted RASS of -5 such as patients on continuous infusion neuromuscular blockade

Related Conditions & MeSH terms

• Critical Illness
• Mechanical Ventilation
• Sedation

Intervention

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

Locations

Country	Name	City	State
Saudi Arabia	King Faisal Specialist Hospital and Research Centre	Riyadh

Sponsors (1)

Lead Sponsor	Collaborator
King Faisal Specialist Hospital & Research Center

Country where clinical trial is conducted

Saudi Arabia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of Delirium	Rate of positive Confusion Assessment Method in Intensive Care Unit (CAM-ICU)	48 hours after randomization
Other	The use of anti-psychotics	Rate of using anti-psychotics for confirmed ICU-acquired delirium	48 hours after randomization
Other	Use of Physical restraints	Use of physical restraints	48 hours after randomization
Other	Mortality	Death that occurs during 28 days	28 days after randomization
Primary	Duration of Mechanical Ventilation	To assess whether ketamine can help to shorten the time of being in breathing tube and ventilator (duration of mechanical ventilation )	From Intubation to extubation date and off Mechanical Ventilation or until ICU discharge, death, or 28 days post randomization whichever occurs first.
Secondary	Cumulative Sedation Dosages	To compare the cumulative dose of pain and sedative medications.	First 48 hours after randomization
Secondary	Dexmedetomidine use	To compare the number of patients started on dexmedetomidine.	First 48 hours after randomization
Secondary	Richmond Agitation Sedation Score (RASS)	To compare The number of patients are in RASS score goal.	First 48 hours after randomization
Secondary	Pain score	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.	First 48 hours after randomization
Secondary	Vasopressor Medication Dosages	To compare vasopressor requirement.	First 48 hours after randomization.
Secondary	Hemodynamics	Changes in Mean Arterial Blood Pressure (MAP) and Heart Rate (HR)	First 48 hours after randomization
Secondary	Frequency of endotracheal tube Suctioning	Proportion of patient with changes in requirements of suctioning frequency to 2 hours of less	First 48 hours after randomization
Secondary	Hospital Length of Stay (LOS)	To compare hospital LOS	Throughout study completion (1 year)
Secondary	ICU Length of stay (LOS)	To compare ICU LOS	Throughout study completion (1 year)
Secondary	Tracheostomy	Tracheostomy rate	28 days after randomization
Secondary	Unplanned extubation	Rate of unplanned extubation	28 days after randomization
Secondary	Re-intubation rate	Rate of unplanned and unexpected re-intubation	28 days after randomization