Dexmedetomidine for Prolonged Sedation in PICUs (PROSDEX)

January 18, 2019 updated by: angela amigoni, Azienda Ospedaliera di Padova

Efficacy and Safety of Dexmedetomidine for Prolonged Sedation in Pediatric Intensive Care Units

Sedation management of the critically ill patients is still a challenge for the pediatric intensivists. Worldwide the most common sedation approach includes the concomitant use of opioids and benzodiazepines. The use of these drugs is associated with adverse events contributing with morbidity, such as decreased spontaneous ventilation, withdrawal syndrome and delirium onset. Moreover, benzodiazepine demonstrated a neurotoxic apoptotic effect that could potentially impact neurocognitive outcome.

Dexmedetomidine (DEX) is a selective alpha-2-adrenergic agonist with sedative, analgesic and anxiolytic effects. Its unique pharmacological profile allows reaching a conscious sedation state with minimal respiratory depression, promoting faster ventilation weaning and better collaboration with the medical staff. Moreover, DEX seems to present adjuvant properties towards withdrawal syndrome and delirium. Finally, some studies in animals suggested that Dexmedetomidine might have a role of neuro-protection, especially in a contest of cerebral ischemia.

Currently, the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved DEX only for the adult population and for sedation lasting not more than 24 hours. The Italian Medicines Agency (AIFA), in January 2016, approve DEX in children for specific indications including difficult sedation in mechanically ventilated critically ill patients. Up to now, few data are still available regarding its efficacy and safety for prolonged sedation in Pediatric Intensive Care Units (PICUs) and no studies have reported the use of DEX after AIFA's approval so far.

Aims of the study are:

to evaluate the characteristics of DEX use for prolonged sedation ≥24 hours in critically ill children (indication, dosages, time of infusion, time of infusion weaning, association with other drugs); to evaluate its efficacy in terms of comfort and conventional drug sparing, using standardized and validate measures; further, to evaluate its efficacy in terms of reduction of incidence of withdrawal syndrome and delirium; to evaluate its safety profile collecting any adverse event potentially correlated with its administration; to define if efficacy and safety could differ among approved indications versus not-approved ones.

Design: Multicenter observational prospective study, involving tertiary-care PICUs.

Study period: From January 2016 up to reaching of the calculated sample size (N patients =163).

Population: All critically ill patients <18 years who received prolonged sedation including DEX for ≥24 hours. In case of multiple infusions, only data regarding the first infusion will be included. Exclusion criteria: extreme prematurity (<28 weeks of gestational age), hypersensitivity to the active substance, incomplete data form. .

Collecting data strategy: Data will be prospectively collected from each Institution by means of a anonymous standardized form completed by two different investigators per center. For each patient, the following variables will be collected:

demographics characteristics (age, gender, race, weight) and clinical features (main diagnosis, associated morbidities, PIM3 score ad admission, number of high intensity interventions during PICU-stay, mechanical ventilation features, inotropic drugs use, length of stay, survival at discharge); DEX administration characteristics (indication, loading dose, minimum and maximum dosages, duration of DEX infusion, duration of DEX infusion weaning) and information on concomitant use of analgesics or sedative drugs (name of drugs and respective dosages at DEX starting time and 24 hours later); clinical scores of analgesia and sedation (Comfort Behavior Scale, CBS), withdrawal syndrome (Withdrawal Assessment Toll-1, WAT-1) and delirium (Cornell Assessment of Pediatric Delirium, CAPD) depending on the respective indication, registered immediate pre-DEX and 24 hours later; any adverse event potentially related to DEX administration and any related intervention, if present. In particular, we the investigators evaluate if bradycardia, hypotension (with or without poor perfusion), hypertension, agitations or other events are registered during the infusion. Further, investigators will register if any sign of DEX withdrawal (tachycardia, hypertension, agitation, other) are present immediately after the infusion.

Statistical analysis: Descriptive and analytic statistics will be performed according with the variable characteristics. A causal multivariate model will be developed to identify any significant risk or protective factors towards adverse outcomes (ineffective sedation, onset of adverse events).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Actual)

163

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Alessandria, Italy
        • Pediatric Intensive Care Unit, Children's Hospital C.Arrigo, Alessandria, Italy
      • Bergamo, Italy
        • Pediatric Intensive Care Unit, ASST John XXIII Pope Hospital, Bergamo, Italy
      • Bologna, Italy
        • Pediatric Intensive Care Unit, S.Orsola Malpighi Hospital, University of Bologna, Italy
      • Milano, Italy
        • Pediatric Intensive Care Unit, Children's Hospital V.Buzzi, Milan, Italy
      • Novara, Italy
        • Pediatric and Neonatal Intensive Care Unit, Maggiore della Carità Hospital, Novara, Italy
      • Padova, Italy, 35127
        • Terapia Intensiva Pediatrica Azienda Ospedaliera di Padova
      • Roma, Italy
        • Pediatric Intensive Care Unit, Bambino Gesù Children's Hospital, Rome, Italy
      • Rome, Italy
        • Pediatric Intensive Care Unit, A.Gemelli Hospital, Sacro Cuore Catholic University, Rome Italy
      • Trieste, Italy
        • Pediatric Intensive Care Unit, Burlo Garofalo Hospital, University of Trieste, Italy

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Critically ill children admitted to PICU

Description

Inclusion Criteria:

  • age <18 years
  • admission to PICU
  • sedation with dexmedetomidine lasted more than 24 hours
  • written informed consent

Exclusion Criteria:

  • extreme prematurity (<28 weeks of gestational age)
  • hypersensitivity to the active substance
  • incomplete data regarding outcome measures

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
dex group
Critically ill patients <18 year-old receiving prolonged sedation with endovenous dexmedetomidine (dosage 0.2 mcg/Kg/hour to 1.8 mcg/Kg/hour) more than 24 hours
Drug: Dexmedetomidine
Other Names:
  • precedex
  • dexdor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comfort Behavior Scale (CBS)
Time Frame: Immediately before DEX start and 24 hours later
Standardized validated score for sedation level and pain assessment; range 6-30; lower values represent a deep level of sedation
Immediately before DEX start and 24 hours later

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Opioid and benzodiazepines dosage
Time Frame: Immediately before DEX start and 24 hours later.
Opioid and benzodiazepines cumulative and maximal dosage
Immediately before DEX start and 24 hours later.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Withdrawal Assessment Tool-1
Time Frame: Immediately before DEX start and 24 hours later.
Standardized validated score for the assessment of withdrawal syndrome; range 0-12; higher values represent a more severe withdrawal syndrome; withdrawal syndrome is probable if score is > 2
Immediately before DEX start and 24 hours later.
Cornell Assessment of Pediatric Delirium, CAPD
Time Frame: Immediately before DEX start and 24 hours later
Standardized validated score for the assessment of pediatric delirium; range 0-32; higher scores represent a more severe presence of delirium; delirium is probable if score is > 8
Immediately before DEX start and 24 hours later
Onset of adverse events
Time Frame: During and immediately after dexmedetomidine infusion.
any adverse event potentially related with DEX-administration
During and immediately after dexmedetomidine infusion.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Azienda Ospedaliera di Padova

Collaborators

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Investigators

  • Principal Investigator: angela amigoni, MD, Azienda Ospedaliera Di Padova

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2016

Primary Completion (Actual)

December 31, 2018

Study Completion (Actual)

December 31, 2018

Study Registration Dates

First Submitted

November 29, 2018

First Submitted That Met QC Criteria

November 29, 2018

First Posted (Actual)

December 3, 2018

Study Record Updates

Last Update Posted (Actual)

January 23, 2019

Last Update Submitted That Met QC Criteria

January 18, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 4466/AO/18; AOP1403

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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