KETASER01 protocol: What went right and what went wrong.

OBJECTIVE: To discuss the results of the KETASER01 trial and the reasons for its failure, particularly in view of future studies. METHODS: KETASER01 is a multicenter, randomized, controlled, open-label, sequentially designed, non-profit Italian study that aimed to assess the efficacy of ketamine compared with conventional anesthetics in the treatment of refractory convulsive status epilepticus (RCSE) in children. RESULTS: During the 5-year recruitment phase, a total of 76 RCSEs treated with third-line therapy were observed in five of the 10 participating Centers; only 10 individuals (five for each study arm; five females, mean age 6.5 ± 6.3 years) were enrolled in the KETASER01 study. Two of the five patients (40%) in the experimental arm were successfully treated with ketamine and two of the five (40%) children in the control arm, where successfully treated with thiopental. In the remaining six (60%) enrolled patients, RCSE was not controlled by the randomized anesthetic(s). SIGNIFICANCE: The KETASER01 study was prematurely halted due to low eligibility of patients and no successful recruitment. No conclusions can be drawn regarding the objectives of the study. Here, we discuss the KETASER01 results and critically analyze the reasons for its failure in view of future trials.

Efficacy of ketamine in refractory convulsive status epilepticus in children: a protocol for a sequential design, multicentre, randomised, controlled, open-label, non-profit trial (KETASER01).

INTRODUCTION: Status epilepticus (SE) is a life-threatening neurological emergency. SE lasting longer than 120 min and not responding to first-line and second-line antiepileptic drugs is defined as 'refractory' (RCSE) and requires intensive care unit treatment. There is currently neither evidence nor consensus to guide either the optimal choice of therapy or treatment goals for RCSE, which is generally treated with coma induction using conventional anaesthetics (high dose midazolam, thiopental and/or propofol). Increasing evidence indicates that ketamine (KE), a strong N-methyl-d-aspartate glutamate receptor antagonist, may be effective in treating RCSE. We hypothesised that intravenous KE is more efficacious and safer than conventional anaesthetics in treating RCSE. METHODS AND ANALYSIS: A multicentre, randomised, controlled, open-label, non-profit, sequentially designed study will be conducted to assess the efficacy of KE compared with conventional anaesthetics in the treatment of RCSE in children. 10 Italian centres/hospitals are involved in enrolling 57 patients aged 1 month to 18 years with RCSE. Primary outcome is the resolution of SE up to 24 hours after withdrawal of therapy and is updated for each patient treated according to the sequential method. ETHICS AND DISSEMINATION: The study received ethical approval from the Tuscan Paediatric Ethics Committee (12/2015). The results of this study will be published in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: NCT02431663; Pre-results.

Neonatal liver abscesses due to Candida infection effectively treated with caspofungin.

UNLABELLED: Candidiasis is relatively frequent in neonatal and pediatric intensive care units (ICUs), particularly in preterm infants less than 28 weeks of gestational age. Neonatal candidiasis shows high mortality and is often associated to poor neurodevelopmental prognosis in survivor patients. Amphotericin B and fluconazole are the first choice drugs for the treatment of neonatal candidiasis. Caspofungin is an alternative antifungal agent, which is recommended for invasive candidiasis in adults, but has been poorly experienced in neonates and infants as far as now. We report the first two infants with Candida liver abscesses treated with caspofungin. In the first infant bloodstream and liver lesions were cleared by combination therapy with fluconazole, liposomal amphotericin and caspofungin, while in the second one by caspofungin alone. CONCLUSION: Our observations confirm the efficacy and tolerability of caspofungin in the treatment of neonatal candidiasis refractory to conventional antifungal drugs. More extensive data are recommended in order to asses a specific neonatal schedule.