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

S

Scientific Institute for Research Hospitalization and Healthcare (IRCCS)

Status and phase

Terminated
Phase 2

Conditions

Withdrawal Syndrome

Treatments

Drug: Placebo
Drug: Dexmedetomidine

Study type

Interventional

Funder types

Other

Identifiers

NCT03645603
EudraCT 2015-002114-80 OsSC

Details and patient eligibility

About

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.

Full 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.

Enrollment

45 patients

Sex

All

Ages

7 days to 18 years old

Volunteers

No 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

Exclusion criteria

  • Hemodynamic instability
  • Cardiac bundle-branch block of 2 or 3 degree
  • Hypersensitivity to the alpha-agonists
  • Persistent fever of unknown origin or sensitivity to malignant hyperthermia
  • Use of alpha-agonist (clonidine or dexmedetomidine) in the last 30 days

Trial design

Primary purpose

Prevention

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

45 participants in 2 patient groups, including a placebo group

Dexmedetomidine
Experimental group
Description:
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.
Treatment:
Drug: Dexmedetomidine
Placebo
Placebo Comparator group
Description:
saline solution for IV infusion. The administration of infusion will follow the experimental drug.
Treatment:
Drug: Placebo

Trial documents
1

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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