Efficacy and safety of eslicarbazepine acetate versus controlled-release carbamazepine monotherapy in newly diagnosed epilepsy: A phase III double-blind, randomized, parallel-group, multicenter study.

OBJECTIVE: We assessed the efficacy and safety of once-daily eslicarbazepine acetate in comparison with twice-daily (BID) controlled-release carbamazepine (carbamazepine-CR) monotherapy in newly diagnosed focal epilepsy patients. METHODS: This randomized, double-blind, noninferiority trial (NCT01162460) utilized a stepwise design with 3 dose levels. Patients who remained seizure-free for the 26-week evaluation period (level A: eslicarbazepine acetate 800 mg/carbamazepine-CR 200 mg BID) entered a 6-month maintenance period. If a seizure occurred during the evaluation period, patients were titrated to the next target level (level B: eslicarbazepine acetate 1200 mg/carbamazepine-CR 400 mg BID, level C: eslicarbazepine acetate 1600 mg/carbamazepine-CR 600 mg BID) and the evaluation period began again. The primary endpoint was the proportion of seizure-free patients for 6 months after stabilization in the per protocol set. The predefined noninferiority criteria were -12% absolute and -20% relative difference between treatment groups. RESULTS: Eight hundred fifteen patients were randomly assigned; 785 (388 in the eslicarbazepine acetate group and 397 in the carbamazepine-CR group) were included in the per protocol set, and 813 (401 in the eslicarbazepine acetate group and 412 in the carbamazepine-CR group) were included in the full analysis set for the primary analysis. Overall, 71.1% of eslicarbazepine acetate-treated patients and 75.6% of carbamazepine-CR-treated patients were seizure-free for ≥6 months at the last evaluated dose (average risk difference = -4.28%, 95% confidence interval [CI] = -10.30 to 1.74; relative risk difference = -5.87%, 95% CI = -13.50 to 2.44) in the per protocol set. Rates of treatment-emergent adverse events were similar between groups for patients in the safety set. Noninferiority was also demonstrated in the full analysis set, as 70.8% of patients with eslicarbazepine acetate and 74.0% with carbamazepine-CR were seizure-free at the last evaluated dose (average risk difference = -3.07, 95% CI = -9.04 to 2.89). SIGNIFICANCE: Treatment with eslicarbazepine acetate was noninferior to BID carbamazepine-CR. With its once-daily formulation, eslicarbazepine acetate provides a useful option for first-line monotherapy for adults with newly diagnosed epilepsy and focal onset seizures.

Concept for a study design in patients with severe community-acquired pneumonia: A randomised controlled trial with a novel IGM-enriched immunoglobulin preparation - The CIGMA study.

INTRODUCTION: Severe community-acquired pneumonia is defined as community-acquired pneumonia that requires intensive medical care. Mortality in these patients is still high depending on time and admission. Since bad outcomes may occur despite antibiotic therapy to treat severe community-acquired pneumonia, the focus has shifted to targeting the host response. The CIGMA Study examines the safety and efficacy of the novel IgM-enriched immunoglobulin preparation BT086 when added to standard of care treatment. METHODS/DESIGN: The aim of this multicentre, randomised, placebo-controlled, double-blind, parallel-group, adaptive group-sequential phase II study is to determine the efficacy and safety of BT086, an IgM-enriched immunoglobulin preparation, as an adjunctive treatment in mechanically-ventilated patients with severe community-acquired pneumonia. The increase of ventilator-free days is the primary endpoint in this study. For this trial, ventilator-free days are defined as the number of days between successful extubation from endotracheal ventilation and day 28 after enrolment of the patient into the study. Two interim analyses were considered for this study. DISCUSSION: Several novel agents for treatment of sepsis have been evaluated in the last two decades; however, none has significantly reduced mortality rates. Failure was attributed to the heterogeneity of septic patients or sepsis. Severe community-acquired pneumonia was chosen as the indication for this study to increase homogeneity within this patient population. TRIAL REGISTRATION: EUDRACT 2010-022380-35.