Efficacy and Safety of Dexmedetomidine During Weaning From Analgesia and Sedation in PICU (TIP-15-01)

Sponsor

IRCCS Azienda Ospedaliero-Universitaria di Bologna (Other)

Overall Status

Terminated

CT.gov ID

NCT03645603

Collaborator

Azienda Ospedaliera di Padova (Other), Fondazione Policlinico Universitario Agostino Gemelli IRCCS (Other)

Enrollment

Location

Arms

16.6

Actual Duration (Months)

2.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This interventional study evaluates the efficacy of dexmedetomidine during weaning from analgesic and sedative drugs in reducing the occurrence of the withdrawal syndrome in PICU. All enrolled patients will undergo the same weaning regimen one half will receive dexmedetomidine while the other will receive a placebo.

Condition or Disease	Intervention/Treatment	Phase
Withdrawal Syndrome	Drug: Dexmedetomidine Drug: Placebo	Phase 2

Detailed Description

Children admitted to PICU need of analgesic and sedative drugs. Prolonged treatment can lead to undesirable effects as dependence and tolerance. Patients that have developed dependence may develop the withdrawal syndrome (WS) during the analgesics and sedatives weaning process.

Withdrawal symptoms are due to central nervous system excitement, gastrointestinal disturbance, and sympathetic system activation. The incidence of withdrawal syndrome is variable between 17 and 57% a recent study reported an incidence of 64.6% of WS in Italian PICUs. The prevention strategies are addressed to the restriction of drug exposure and to the gradual tapering of infusion. However, these strategies have weak evidence of effectiveness. In this study, the investigators hypothesize that dexmedetomidine may be useful and effective during the weaning of analgosedation drugs in PICU, in preventing the withdrawal syndrome. The primary aim of the study is to evaluate the efficacy of dexmedetomidine in reducing the occurrence of the WS. Secondary aims are to evaluate the dexmedetomidine safety during the weaning, the effective dose range, and the efficacy in reducing the duration of the weaning, of the mechanical ventilation, and of the length of PICU stay. Efficacy will be compared among pediatric age groups, gender, race, Pediatric Index of Mortality (PIM3) score, and length of the analgosedation treatment.

Patients admitted to the PICU that meets the inclusion criteria, will be randomly assigned to one of the two treatment groups: treatment A (dexmedetomidine) or treatment B (placebo).

Twenty-four hours before the start of the weaning an intravenous infusion of dexmedetomidine/placebo will start. After 24 hours of dexmedetomidine infusion, the weaning regimen will begin following the subsequent indications: 10% reduction of the dose every 12 hours. The withdrawal assessment tool version 1 (WAT-1) is the selected scale to evaluate the occurrence of the WS. Patients with a score of WAT-1 <3 continue the weaning regimen. Patients with a score ≥3 increase the dose of dexmedetomidine/placebo until the next WAT-1 score control and temporarily stop the planned 10% dose reduction. If the next WAT-1 score decreased by at least 1 point from the previous score, the weaning program restarted (10% reduction) without further changes in the dose of dexmedetomidine/placebo until the subsequent score. The 'acute withdrawal crisis' will be treated with a rescue dose of the opioid and/or benzodiazepine in use repeatable until resolution of the crisis. Once analgesics and sedatives weaning is complete, dexmedetomidine will gradually discontinue. Five days after discharge from PICU, a follow-up visit will be performed.

The sample size estimate is 80 participants for each of the two groups for a total of 160 patients recruited within a period of two years.

Study Design

Study Type:

Interventional

Actual Enrollment :

45 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

Efficacy and Safety of Dexmedetomidine During Weaning From Analgesia and Sedation in Pediatric Intensive Care Unit. A Multicenter, Double-blind, Randomized Controlled Trial.

Actual Study Start Date :

Aug 30, 2018

Actual Primary Completion Date :

Jan 18, 2020

Actual Study Completion Date :

Jan 18, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dexmedetomidine Dexmedetomidine 100 mcg/ml concentrate solution. Continuous iv infusion. Start dose 0.4 mcg/kg/h, increases by 0.2 mcg/kg/h until 0.8 mcg/kg/h (half dose for neonates). If withdrawal symptoms appear the dose can be increased to a maximum of 1.4 mcg/Kg/h.	Drug: Dexmedetomidine intravenous infusion Other Names: Dexdor, Precedex
Placebo Comparator: Placebo saline solution for IV infusion. The administration of infusion will follow the experimental drug.	Drug: Placebo intravenous infusion of physiological saline solution to mimic dexmedetomidine infusion Other Names: physiological saline solution

Arm

Intervention/Treatment

Experimental: Dexmedetomidine

Dexmedetomidine 100 mcg/ml concentrate solution. Continuous iv infusion. Start dose 0.4 mcg/kg/h, increases by 0.2 mcg/kg/h until 0.8 mcg/kg/h (half dose for neonates). If withdrawal symptoms appear the dose can be increased to a maximum of 1.4 mcg/Kg/h.

Drug: Dexmedetomidine

intravenous infusion

Other Names:

Dexdor, Precedex

Placebo Comparator: Placebo

saline solution for IV infusion. The administration of infusion will follow the experimental drug.

Drug: Placebo

intravenous infusion of physiological saline solution to mimic dexmedetomidine infusion

Other Names:

physiological saline solution

Outcome Measures

Primary Outcome Measures

Change in Withdrawal Assessment Tool (WAT-1) scale [time 0 start dexmedetomidine and every 12 hours post-start dexmedetomidine for 7 days]
WAT-1 score recorded every 12 hours.The score ranges from 0 to 12, a score ≥3 indicates the presence of signs/symptoms of withdrawal.

Secondary Outcome Measures

Change in heart rate [0,1, 2, 12, 24 hours post-start dexmedetomidine and then every 12 hours for 7 days]
changes in heart rate will be recorded when their value differs more than 20% by the patient's baseline values.
Change in Systolic Blood Pressure [0,1, 2, 12, 24 hours post-start dexmedetomidine and then every 12 hours for 7 days]
changes in Systolic Blood Pressure will be recorded when their value differs more than 20% by the patient's baseline values.
Change in Diastolic Blood Pressure [0,1, 2, 12, 24 hours post-start dexmedetomidine and then every 12 hours for 7 days]
changes in Diastolic Blood Pressure will be recorded when their value differs more than 20% by the patient's baseline values.

Other Outcome Measures

Change in Opioid dose [7 days]
verification of adherence to weaning regimen
Change in Sedative dose [7 days]
verification of adherence to weaning regimen

Eligibility Criteria

Criteria

Ages Eligible for Study:

7 Days to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Continuous analgesic and sedative endovenous treatment for at least 5 days
Invasive or non-invasive mechanical ventilation
Clinical conditions that allow by clinical judgment the start of analgosedation weaning
Post-natal age ≥ 7 days and PMA beyond the 37 weeks
Written informed consent obtained