Prolonged Sedation Clinical Trial
— PROSDEXOfficial title:
Efficacy and Safety of Dexmedetomidine for Prolonged Sedation in Pediatric Intensive Care Units
| Verified date | January 2019 |
| Source | Azienda Ospedaliera di Padova |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Observational |
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).
| Status | Completed |
| Enrollment | 163 |
| Est. completion date | December 31, 2018 |
| Est. primary completion date | December 31, 2018 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | N/A to 18 Years |
| Eligibility |
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 |
| Country | Name | City | State |
|---|---|---|---|
| Italy | Pediatric Intensive Care Unit, Children's Hospital C.Arrigo, Alessandria, Italy | Alessandria | |
| Italy | Pediatric Intensive Care Unit, ASST John XXIII Pope Hospital, Bergamo, Italy | Bergamo | |
| Italy | Pediatric Intensive Care Unit, S.Orsola Malpighi Hospital, University of Bologna, Italy | Bologna | |
| Italy | Pediatric Intensive Care Unit, Children's Hospital V.Buzzi, Milan, Italy | Milano | |
| Italy | Pediatric and Neonatal Intensive Care Unit, Maggiore della Carità Hospital, Novara, Italy | Novara | |
| Italy | Terapia Intensiva Pediatrica Azienda Ospedaliera di Padova | Padova | |
| Italy | Pediatric Intensive Care Unit, Bambino Gesù Children's Hospital, Rome, Italy | Roma | |
| Italy | Pediatric Intensive Care Unit, A.Gemelli Hospital, Sacro Cuore Catholic University, Rome Italy | Rome | |
| Italy | Pediatric Intensive Care Unit, Burlo Garofalo Hospital, University of Trieste, Italy | Trieste |
| Lead Sponsor | Collaborator |
|---|---|
| Azienda Ospedaliera di Padova | Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi |
Italy,
Grant MJ, Schneider JB, Asaro LA, Dodson BL, Hall BA, Simone SL, Cowl AS, Munkwitz MM, Wypij D, Curley MA; Randomized Evaluation of Sedation Titration for Respiratory Failure Study Investigators. Dexmedetomidine Use in Critically Ill Children With Acute R — View Citation
Mason KP, Lerman J. Review article: Dexmedetomidine in children: current knowledge and future applications. Anesth Analg. 2011 Nov;113(5):1129-42. doi: 10.1213/ANE.0b013e31822b8629. Epub 2011 Aug 4. Review. — View Citation
Mondardini MC, Astuto M, Amigoni A. Inclusion of dexmedetomidine for pediatric indications in the list of medicinal products issued by the National Law 648/96. Minerva Anestesiol. 2017 Aug;83(8):891-892. doi: 10.23736/S0375-9393.17.11975-9. Epub 2017 Mar — View Citation
Romagnoli S, Amigoni A, Blangetti I, Casella G, Chelazzi C, Forfori F, Garisto C, Mondardini MC, Moltrasio M, Pasero D, Principi T, Ricci Z, Tarantino F, Conti G. Light sedation with dexmedetomidine: a practical approach for the intensivist in different I — View Citation
Sperotto F, Mondardini MC, Vitale F, Daverio M, Campagnano E, Ferrero F, Rossetti E, Vasile B, Dusio MP, Ferrario S, Savron F, Brugnaro L, Amigoni A; Pediatric Neurological Protection and Drugs (PeNPAD) Study Group. Prolonged sedation in critically ill ch — View Citation
Tabacco B, Tacconi C, Amigoni A. Survey on monitoring analgesia and sedation in the Italian Pediatric Intensive Care Units. Minerva Anestesiol. 2017 Oct;83(10):1010-1016. doi: 10.23736/S0375-9393.17.11707-4. Epub 2017 Mar 28. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Withdrawal Assessment Tool-1 | 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. | |
| Other | Cornell Assessment of Pediatric Delirium, CAPD | 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 | |
| Other | Onset of adverse events | any adverse event potentially related with DEX-administration | During and immediately after dexmedetomidine infusion. | |
| Primary | Comfort Behavior Scale (CBS) | 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 | Opioid and benzodiazepines dosage | Opioid and benzodiazepines cumulative and maximal dosage | Immediately before DEX start and 24 hours later. |