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

Ketamine-Midazolam Versus Morphine-Midazolam for Continous Patient Sedation in Intensive Care Units in Uganda. A Randomised Controlled Trial.

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.

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Study Overview

• Status: Terminated
• Conditions: Critical Illness
• Intervention / Treatment: Combination product: Ketamine-Midazolam; Combination product: Morphine -Midazolam

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Uganda
  • Central
    • Kampala, Central, Uganda, 256
      • Mulago National Referral Hospital ICU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketamine-midazolam; Continous intravenous sedation with a colorless drug mixture in 50ml syringe containing 900mg ketamine and 36mg midazolam.	Combination product: Ketamine-Midazolam; Continous intravenous sedation with 36mg of Midazolam and 900mg of Ketamine mixed in 50ml syringes as long as patient still requires sedation.
Active Comparator: Morphine-Midazolam; Continous intravenous sedation with a colourless drug mixture in 50ml syringes containing 54mg morphine and 36mg midazolam.	Combination product: Morphine -Midazolam; Continous intravenous sedation with 54mg of Morphine Sulphate and 36mg of midazolam mixed in 50ml syringes as long as participant still requires sedation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
duration of mechanical ventilation	in hours from start of mechanical ventialtion	14 days
incidence of hypotension	incidence of hypotension requiring vasopressor support.	14 days
incidence of delirium	assessed daily with the CAM-ICU score	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU length of stay	length of stay in the intensive care unit from enrollment.	14 days
mortality rate	number of deaths in each study arm	within 14 days

Collaborators and Investigators

• Sponsor: Makerere University
• Collaborators: THRiVE
• Investigators: Principal Investigator: Christine Namata, MBChB, Makerere University

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2017
• Primary Completion (Actual): June 15, 2019
• Study Completion (Actual): July 30, 2019

Study Registration Dates

• First Submitted: June 5, 2017
• First Submitted That Met QC Criteria: January 22, 2018
• First Posted (Actual): January 23, 2018

Study Record Updates

• Last Update Posted (Actual): August 28, 2019
• Last Update Submitted That Met QC Criteria: August 26, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Analgesics, Opioid; Narcotics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Ketamine; Midazolam; Morphine
• Other Study ID Numbers: 2015/HD07/1275U

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes