BackgroundAbdominal aortic aneurysm (AAA) is a slowly progressive destructive process of the main abdominal artery. Experimental studies indicate that fibrates exert beneficial effects on AAAs by mechanisms involving both serum lipid modification and favourable changes to the AAA wall.Methods/designFenofibrate in the management of AbdoMinal aortic anEurysm (FAME) is a multicentre, randomised, double-blind, placebo-controlled clinical trial to assess the effect of orally administered therapy with fenofibrate on key pathological markers of AAA in patients undergoing open AAA repair. A total of 42 participants scheduled for an elective open AAA repair will be randomly assigned to either 145 mg of fenofibrate per day or identical placebo for a minimum period of 2 weeks prior to surgery. Primary outcome measures will be macrophage number and osteopontin (OPN) concentration within the AAA wall as well as serum concentrations of OPN. Secondary outcome measures will include levels of matrix metalloproteinases and proinflammatory cytokines within the AAA wall, periaortic fat and intramural thrombus and circulating concentrations of AAA biomarkers.DiscussionAt present, there is no recognised medical therapy to limit AAA progression. The FAME trial aims to assess the ability of fenofibrate to alter tissue markers of AAA pathology.Trial registrationAustralian New Zealand Clinical Trials Registry, ACTRN12612001226897. Registered on 20 November 2012.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1752-z) contains supplementary material, which is available to authorized users.

Purpose: To investigate the feasibility of adaptive dosing and the impact of pharmacogenetic variation on 13-cis-retinoic acid (13-cisRA) disposition in high-risk patients with neuroblastoma.Experimental Design: 13-cisRA (160 mg/m 2 or 5.33 mg/kg/d) was administered to 103 patients ages 21years or less and plasma concentrations of 13-cisRA and 4-oxo-13-cisRA quantitated on day 14 of treatment. Seventy-one patients were recruited to a dose adjustment group, targeting a 13-cisRA C max of 2 mmol/L, with dose increases of 25% to 50% implemented for patients with C max values less than 2 mmol/L. A population pharmacokinetic model was applied and polymorphisms in relevant cytochrome P450 genes analyzed. Results: 13-cisRA C max values ranged from 0.42 to 11.2 mmol/L, with 34 of 103 (33%) patients failing to achieve a C max more than 2 mmol/L. Dose increases carried out in 20 patients in the dose adjustment study group led to concentrations more than 2 mmol/L in 18 patients (90%). Eight of 11 (73%) patients less than 12 kg, receiving a dose of 5.33 mg/kg, failed to achieve a C max of 2 mmol/L or more. Significantly, lower C max values were observed for patients treated with 5.33 mg/kg versus 160 mg/m 2 (1.9 AE 1.2 vs. 3.1 AE 2.0 mmol/L; mean AE SD; P ¼ 0.023). C max was higher in patients who swallowed 13-cisRA capsules as compared with receiving the drug extracted from capsules (4.0 AE 2.2 vs. 2.6 AE 1.8 mmol/L; P ¼ 0.0012). The target C max was achieved by 93% (25/27) versus 55% (42/76) of patients in these 2 groups, respectively. No clear relationships were found between genetic variants and 13-cisRA pharmacokinetic parameters. Conclusions: Dosing regimen and method of administration have a marked influence on 13-cisRA plasma concentrations. Body weight-based dosing should not be implemented for children less than 12 kg and pharmacologic data support higher doses for children unable to swallow 13-cisRA capsules.