Efficacy and safety of Dexmedetomidine for prevention of withdrawal syndrome in Pediatric Intensive Care Unit: protocol for an adaptive, multicenter, randomized, double blind, placebo-controlled, non-profit clinical trial

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 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, and to clearly assess its safety. Methods: We will perform an adaptive, multicenter, randomized, double-blind, placebo-controlled trial. Patients <18 years receiving a continuous intravenous analgosedation treatment for at least 5 days and presenting with clinical conditions that allows the analgosedation weaning will be randomly assigned to treatment A (dexmedetomidine) or treatment B (placebo). The treatment will be started 24 hours before the analgosedation-weaning at 0.4 mcg/kg/h, increased of 0.2 mcg/kg/h per hour up to 0.8 mcg/Kg/h (neonate: 0.2 mcg/Kg/h, increased of 0.1 mcg/Kg/h per hour up to 0.4 mcg/Kg/h)and continued throughout the whole weaning-time. The primary endpoint is the efficacy of the treatment, defined by the reduction in WS rate among patients treated with dexmedetomidine comparing with patients treated with placebo. Safety will be assessed collecting any potentially-related adverse event. The sample size assuring a power of 90% is 77 patients for each group (N total=154 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: AIFA ID TIP-15-01.ClinicalTrials.govID NCT03645603, registered on 24 August 2018. Retrospectively registered on EudraCT with ID 2015-002114-80 on 2 Jan 2019.