Adjunctive Clonidine in the Sedation of Mechanically Ventilated Children

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

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.

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.

Intervention(s) in this Clinical Trial

• Drug: clonidine
  • 5 mcg/kg (maximum 200 mcg) enterally every 6 hours
• Drug: placebo
  • Preparation visually identical to clonidine.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: clonidine
• Placebo Comparator: placebo

Primary Measures

• Feasibility of screening procedures.
  • Time Frame: 90 days
    Safety Issue?: No
• Protocol adherence.
  • Time Frame: 90 days
    Safety Issue?: No
• Enrollment rate.
  • Time Frame: 90 days
    Safety Issue?: No
• Timeliness of drug administration.
  • Time Frame: 90 days
    Safety Issue?: No

Secondary Measures

• Sedation and analgesia requirements.
  • Time Frame: 90 days
    Safety Issue?: No
• Opioid and/or benzodiazepine withdrawal symptoms.
  • Time Frame: 90 days
    Safety Issue?: No
• Adverse effects.
  • Time Frame: 90 days
    Safety Issue?: Yes
• Duration of hospital stay.
  • Time Frame: 90 days
    Safety Issue?: No
• Ventilator-free days (number of days alive and breathing unaided within the first 28 days after intubation).
  • Time Frame: 28 days
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 1 Month

Maximum Age for this Clinical Trial: 18 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Hamilton Health Sciences Corporation Other

Overall Clinical Trial Officials and Contacts

Mark C Duffett Principal Investigator Hamilton Health Sciences Corporation  

Overall Contact: Mark C Duffett 905-521-2100 duffett@hhsc.ca

Information obtained from ClinicalTrials.gov on February 08, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00959062

Study ID Number: NIF09213

ClinicalTrials.gov Identifier: NCT00959062

Health Authority: Canada: Health Canada