Adjunctive Clonidine in the Sedation of Mechanically Ventilated Children

Study Overview
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Brief Summary
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Almost all critically ill children who are mechanically ventilated require sedation and analgesia. Providing effective sedation for children in the PICU requires careful balancing of the need for sedation with the adverse effects associated with sedative medications. Clonidine is often used as an adjunctive sedative and analgesic in children but a well designed and adequately powered randomized trial is required to test the effect of clonidine-based sedation. Because there are no large randomized trials of sedation related interventions among critically ill children there are many unknown factors. This pilot trial, focussing on feasibility outcomes will assess the feasibility of, and inform the design of, a larger randomized controlled trial which will focus on clinically important outcomes.

Detailed Description
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Almost all critically ill children who are mechanically ventilated require sedation and analgesia. Providing effective sedation for children in the PICU requires careful balancing of the need for sedation with the adverse effects associated with sedative medications. Inadequate sedation may result in undue pain and suffering for children, ventilator dysynchrony and may risk removal of life sustaining devices. Excess sedation limits patients' interaction with their parents and care-givers and may result in delayed weaning from mechanical ventilation, prolonged PICU stay and the attendant risks of increased morbidity. Critically ill children may also experience withdrawal when these medications are stopped. Randomized trails in adults have shown that sedation related interventions can improve patients outcomes, but such trials have not been performed in children. Clonidine is often used as an adjunctive sedative and analgesic in children but a well designed and adequately powered randomized trial is required to test the effect of clonidine-based sedation. Because there are no large randomized trials of sedation related interventions among critically ill children there are many unknown factors. This pilot trial, focussing on feasibility outcomes will assess the feasibility of, and inform the design of, a larger randomized controlled trial which will focus on clinically important outcomes.

Official Title
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New Approaches to Pediatric Sedation: Adjunctive Clonidine in the Sedation of Mechanically Ventilated Children (NAPS Pilot Trial)

Conditions
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Respiration, Artificial, Critical Illness, Conscious Sedation, Deep Sedation

Intervention / Treatment
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* Drug: clonidine
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: aged 1 month to 18 years mechanically ventilated the attending physician expects to require mechanical ventilation for at least 2 more days requires sedation in the form of: morphine by continuous infusion or greater than 4 intermittent doses in the previous 24 hours or fentanyl as a continuous infusion AND midazolam or lorazepam by continuous infusion or more than 3 intermittent doses of lorazepam or 6 doses of midazolam in the previous 12 hours has enteral access (gastric or jejunal feeding tube) Exclusion Criteria: hemodynamically unstable meet the American College of Critical Care Medicine hemodynamic definition of shock hypotensive or tachycardic bradycardia, hemodynamically significant cardiac disease or chronic use of anti-hypertensive or diuretic medications a traumatic brain injury on admission chronically (defined as routine administration prior to hospital admission or for greater than 7 days in hospital prior to PICU admission) use benzodiazepines or opioids have received greater than two doses of clonidine within the previous 2 days or dexmedetomidine in the past 2 days were previously enrolled in this study are currently enrolled in a related study are known to be pregnant or breastfeeding are known to be allergic to clonidine or any other ingredient in the tablets or suspension are being considered for organ procurement were chronically (>30 days) ventilated prior to PICU admission are currently receiving, or are expected to initiate the ketogenic diet are receiving cyclosporine or methylphenidate

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: clonidine<br> | Drug: clonidine<br>* 5 mcg/kg (maximum 200 mcg) enterally every 6 hours<br>|
| Placebo Comparator: placebo<br> | Drug: placebo<br>* Preparation visually identical to clonidine.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of screening procedures. |  | 90 days | 
| Protocol adherence. |  | 90 days | 
| Enrollment rate. |  | 90 days | 
| Timeliness of drug administration. |  | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sedation and analgesia requirements. |  | 90 days | 
| Opioid and/or benzodiazepine withdrawal symptoms. |  | 90 days | 
| Adverse effects. |  | 90 days | 
| Duration of hospital stay. |  | 90 days | 
| Ventilator-free days (number of days alive and breathing unaided within the first 28 days after intubation). |  | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pilot Study, Randomized Controlled Trial, Critically Ill, Child, Pediatric, Clonidine, Sedation