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

Study Overview
=================
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. .

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.

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

Conditions
-----------------
Critical Illness

Intervention / Treatment
-----------------
* Combination Product: Ketamine-Midazolam
* Combination Product: Morphine -Midazolam


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age >12years of age. Anticipated need for sedation for >24hours. Exclusion Criteria: Hypertensive crisis i.e. sustained SBP >200mmHg/DBP>110mmHg Status epilepticus Ischemic heart disease and severe LV dysfunction Persistent tachyarrythmias History of mental illness Hypersensitivity to ketamine, morphine or midazolam. 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

Ages Eligible for Study
-----------------
Minimum Age: 12 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomized to either receive ketamine-midazolam or morphine-midazolam for continous sedation at enrollment, then followed up for outcomes.
Masking: Double


Arms and Interventions

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

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 |