Comparing Clinical Outcomes Between Ketamine-midazolam and Morphine-midazolam for Continous Sedation in ICU Patients.

Ketamine

Brief Summary

A prospective, double-blinded, multicenter randomized control trial. All critically ill patients above 12 years of age requiring continuous sedation for \>24hrs in the ICU will be screened and those meeting selection criteria (and consented) will be enrolled into the study. .

Intervention / Treatment

Patients will be randomized to either receive ketamine-midazolam or morphine-midazolam for continous sedation at enrollment, then followed up for outcomes.
  • Ketamine-Midazolam (COMBINATION_PRODUCT)
    Continous intravenous sedation with 36mg of Midazolam and 900mg of Ketamine mixed in 50ml syringes as long as patient still requires sedation.
  • Morphine -Midazolam (COMBINATION_PRODUCT)
    Continous intravenous sedation with 54mg of Morphine Sulphate and 36mg of midazolam mixed in 50ml syringes as long as participant still requires sedation.

Condition or Disease

  • Critical Illness

Phase

  • Phase 2
  • Phase 3

    • Study Design

    Study type: INTERVENTIONAL
    Status: Terminated
    Study results: No Results Available
    Age: 12 Years and older   (Child, Adult, Older Adult)
    Enrollment: 124 (ACTUAL)
    Funded by: Other
    Allocation: Randomized
    Primary Purpose: Treatment

    Masking

    Drugs will be premixed and coded for ketamine-midazolam or morphine-midazolam. The colorless drug mixture shall be provided to the attending physician to start the infusion at 2ml/hour and to be titrated to the desired level of sedation. The investigator and participant will be unaware of which group a certain patient is under.

    DOUBLE:
    • Participant
    • Investigator

    Clinical Trial Dates

    Start date: Oct 22, 2017 ACTUAL
    Primary Completion: Jun 15, 2019 ACTUAL
    Completion Date: Jul 30, 2019 ACTUAL
    Study First Posted: Jan 23, 2018 ACTUAL
    Results First Posted: Aug 31, 2020
    Last Updated: Aug 26, 2019

    Sponsors / Collaborators

    Lead Sponsor: Makerere University
    Lead sponsor is responsible party
    Responsible Party: N/A

    Location

    Central, Uganda
    Kampala, Central, Uganda

    165 participants shall be consecutively randomized into either sedation with ketamine-midazolam or morphine-midazolam group using a block sequence technique; group concealed in brown envelopes. Blinding will be at patient/next of kin level as well as investigator/data collector level.

    Enrolled subjects shall be followed up for treatment history, co-morbidities and related data will be collected, results analyzed and study findings will be availed to ICU physicians and Ministry of health to guide treatment considerations and for health care planning.

    Data shall be collected using a standardized questionnaire by trained research assistants. It will be double entered into Epidata and exported to STATA version 12.0 for analysis. Continuous variables will be expressed as means and standard deviations, while categorical data will be expressed as frequencies with their respective percentages. Linear regression and logistic regression used to analyse primary outcomes, as well as multivariate analysis to detect associations.

    Participant Groups

    • Continous intravenous sedation with a colorless drug mixture in 50ml syringe containing 900mg ketamine and 36mg midazolam.

    • Continous intravenous sedation with a colourless drug mixture in 50ml syringes containing 54mg morphine and 36mg midazolam.

    Eligibility Criteria

    Sex: All
    Minimum Age: 12
    Age Groups: Child / Adult / Older Adult
    Healthy Volunteers: Yes

    Inclusion Criteria:

    1. Age \>12years of age.
    2. Anticipated need for sedation for \>24hours.

    Exclusion Criteria:

    1. Hypertensive crisis i.e. sustained SBP \>200mmHg/DBP\>110mmHg
    2. Status epilepticus
    3. Ischemic heart disease and severe LV dysfunction
    4. Persistent tachyarrythmias
    5. History of mental illness
    6. Hypersensitivity to ketamine, morphine or midazolam.
    7. Tetanus -due to the muscle rigidity that may be caused by ketamine. Reasons for exclusions 1 to 4; Ketamine stimulates the sympathetic nervous system causing transient increase in myocardial work and blood pressure and has psychoactive effects

    Primary Outcomes

    • in hours from start of mechanical ventialtion

    • incidence of hypotension requiring vasopressor support.

    • assessed daily with the CAM-ICU score

    Secondary Outcomes

    • length of stay in the intensive care unit from enrollment.

    • number of deaths in each study arm

    More Details

    NCT Number: NCT03407404
    Acronym: KeMiMof
    Other IDs: 2015/HD07/1275U
    Study URL: https://clinicaltrials.gov/study/NCT03407404
    Last updated: Sep 29, 2023