Efficacy and safety of Dexmedetomidine for prevention of withdrawal syndrome in Pediatric Intensive Care Unit Protocol for a prospective, multicenter, randomized, double blind, placebo-controlled, non-profit clinical trial (TIP-15-01)

Abstract

Background: Prolonged treatment with analgesic and sedative drugs in Pediatric Intensive Care Unit (PICU) may lead to undesirable effects as dependence and tolerance. Moreover, during the analgosedation weaning patients may develop clinical signs of withdrawal, known as withdrawal syndrome (WS). Some studies indicated that dexmedetomidine, a selective α2-adrenoceptors agonist, may be useful to prevent WS, but no clear evidences still support this data. Aims of the present study are to evaluate the efficacy of dexmedetomidine in reducing the occurrence of WS during the analgosedation weaning, to evaluate its safety, to identify its optimal dose-range and to quantify its ability in reducing time of weaning, time of mechanical ventilation and PICU-stay. Methods: We will perform a prospective, multicenter, randomized, double-blind, placebo-controlled study. Patients meeting the inclusion criteria will be randomly assigned to treatment A (dexmedetomidine) or treatment B (placebo). Treatments will be started 24 hours before the analgosedation-weaning and will be continued throughout the whole weaning time. Efficacy of treatments will be evaluated by monitoring the signs of WS using the withdrawal assessment tool version 1 score (WAT-1). If WAT-1 score is ≥3, dexmedetomidine/placebo-dose will be increased following a defined protocol. Thus, efficacy will be compared between treatment groups. Safety will be assessed collecting any potentially-related adverse event. Clinical or sedation characteristics will be analyzed to assess any significant association with outcome measures. The sample size assuring a power of 95% is 80 patients for each group (N total=160 patients). The study was approved by the Ethics Committee of the University-Hospital S.Orsola-Malpighi of Bologna on 22 March 2017. Discussion: The present trial will allow to clearly assess the efficacy of dexmedetomidine in reducing the occurrence of WS during the weaning of analgosedation drugs. In addition, the study will provide a unique insight into the safety profile of dexmedetomidine. Trial registration: ClinicalTrials.gov ID NCT03645603, registered on 24 August 2018, https://clinicaltrials.gov/ct2/show/NCT03645603. Retrospectively registered on EudraCT with ID 2015-002114-80, registered on 2 Jan 2019.