Efficacy and Safety of Ezetimibe Added to Atorvastatin Versus Atorvastatin Uptitration or Switching to Rosuvastatin in Patients With Primary Hypercholesterolemia

Hypercholesterolemic patients (n = 1,547) at high atherosclerotic cardiovascular disease risk with low-density lipoprotein cholesterol (LDL-C) levels 65100 and 64160 mg/dl while treated with atorvastatin 10 mg/day entered a multicenter, randomized, double-blind, active-controlled, clinical trial using two 6-week study periods. Period I compared the efficacy/safety of (1) adding ezetimibe 10 mg (ezetimibe) to stable atorvastatin 10 mg, (2) doubling atorvastatin to 20 mg, or (3) switching to rosuvastatin 10 mg. Subjects in the latter 2 groups who persisted with elevated LDL-C levels ( 65100 and 64160 mg/dl) after period I, entered period II; subjects on atorvastatin 20 mg had ezetimibe added to their atorvastatin 20 mg, or uptitrated their atorvastatin to 40 mg; subjects on rosuvastatin 10 mg switched to atorvastatin 20 mg plus ezetimibe or uptitrated their rosuvastatin to 20 mg. Some subjects on atorvastatin 10 mg plus ezetimibe continued the same treatment into period II. At the end of period I, ezetimibe plus atorvastatin 10 mg reduced LDL-C significantly more than atorvastatin 20 mg or rosuvastatin 10 mg (22.2% vs 9.5% or 13.0%, respectively, p <0.001). At the end of period II, ezetimibe plus atorvastatin 20 mg reduced LDL-C significantly more than atorvastatin 40 mg (17.4% vs 6.9%, p <0.001); switching from rosuvastatin 10 mg to ezetimibe plus atorvastatin 20 mg reduced LDL-C significantly more than uptitrating to rosuvastatin 20 mg (17.1% vs 7.5%, p <0.001). Relative to comparative treatments, ezetimibe added to atorvastatin 10 mg (period I) or atorvastatin 20 mg (period II) produced significantly greater percent attainment of LDL-C targets <100 or <70 mg/dl, and significantly greater percent reductions in total cholesterol, non-high-density lipoprotein cholesterol, most lipid and lipoprotein ratios, and apolipoprotein B (except ezetimibe plus atorvastatin 20 vs atorvastatin 40 mg). Reports of adverse experiences were generally similar among groups. In conclusion, treatment of hypercholesterolemic subjects at high cardiovascular risk with ezetimibe added to atorvastatin 10 or 20 mg produced significantly greater improvements in key lipid parameters and significantly greater attainment of LDL-C treatment targets than doubling atorvastatin or switching to (or doubling) rosuvastatin at the compared doses

The efficacy of montelukast during the allergy season in pediatric patients with persistent asthma and seasonal aeroallergen sensitivity

Objective. To determine the effect of montelukast on asthma during the allergy season in children with persistent asthma and seasonal aeroallergen sensitivity. Design. This 3-week double-blind, placebo-controlled, parallel-group multicenter study compared daily montelukast 5 mg chewable tablets and placebo in patients 6-14 years of age with forced expiratory volume in 1 second (FEV1) 60 and 85% predicted, persistent asthma that is also active during allergy season, and documented sensitivity to seasonal allergens. Concomitant inhaled corticosteroid use was permitted in up to 40% of enrolled patients. The primary endpoint was the percentage change from baseline in FEV1 over 3 weeks of treatment. Additional endpoints included the percentage change from baseline in -agonist use, average changes in daytime and nighttime symptom score, AM and PM peak expiratory flow rate (PEFR), investigator&apos;s global asthma evaluation, and parent/guardian global asthma evaluation at the end of the treatment period. Adverse experiences (AEs) were collected to assess safety and tolerability. Results. A total of 421 patients were randomized to montelukast (N = 203) or placebo (N = 218). For the primary endpoint, the percentage change from baseline FEV1, montelukast was not significantly different from placebo (least squares mean 9.53% vs. 9.15%, respectively; p = 0.810). Compared with placebo, montelukast was associated with significantly lower (better) investigator&apos;s global asthma evaluation (LS mean 2.71 vs. 2.98; p 0.05) and parent/guardian global asthma evaluation (LS mean: 2.63 vs. 2.90; p 0.05) scores. There were no significant differences between treatment groups for the other efficacy evaluations. Both treatments were well tolerated, with no significant differences observed in AE rates. Conclusion. Montelukast did not significantly improve FEV1 compared with placebo over three weeks of treatment during the allergy season in pediatric patients with seasonal allergen sensitivity

Bowel colonization with resistant gram-negative bacilli after antimicrobial therapy of intra-abdominal infections: observations from two randomized comparative clinical trials of ertapenem therapy

Abstract The selection of resistant gram-negative bacilli by broad-spectrum antibiotic use is a major issue in infection control. The aim of this comparative study was to assess the impact of different antimicrobial regimens commonly used to treat intra-abdominal infections on the susceptibility patterns of gram-negative bowel flora after completion of therapy. In two international randomized open-label trials with laboratory blinding, adults with complicated intra-abdominal infection requiring surgery received piperacillin-tazobactam (OASIS I) or ceftriaxone/metronidazole (OASIS II) versus ertapenem for 4-14 days. Rectal swabs were obtained at baseline, end of therapy, and 2 weeks post-therapy. Escherichia coli and Klebsiella spp. were tested for production of extended-spectrum β-lactamase (ESBL). Enterobacteriaceae resistant to the agent used were recovered from 19 of 156 (12.2%) piperacillin-tazobactam recipients at the end of therapy compared to 1 (0.6%) patient at baseline (p&lt;0.001) in OASIS I, and from 33 of 193 (17.1%) ceftriaxone/metronidazole recipients at the end of therapy compared to 5 (2.6%) patients at baseline (p&lt;0.001) in OASIS II. Ertapenem-resistant Enterobacteriaceae were recovered from 1 of 155 and 1 of 196 ertapenem recipients at the end of therapy versus 0 and 1 ertapenem recipients M. J. DiNubile ( ) · I

Comparison of an aprepitant regimen with a multiple-day ondansetron regimen, both with dexamethasone, for antiemetic efficacy in high-dose cisplatin treatment

Background: We compared an aprepitant regimen with a control regimen of ondansetron + dexamethasone given for 4 days. Patients and methods: Patients scheduled to receive cisplatin ‡70 mg/m 2 were randomized to either the aprepitant regimen (aprepitant, ondansetron and dexamethasone on day 1; aprepitant and dexamethasone on days 2-3; dexamethasone on day 4) or control regimen (ondansetron + dexamethasone on days 1-4). Patients recorded vomiting, nausea and rescue therapy use. The primary end point was complete response (no vomiting and no use of rescue therapy) in the overall phase (days 1-5 post-cisplatin). Results: Complete response rates were higher in the aprepitant than control group in the overall (72% versus 61%; P = 0.003), acute (day 1; 88% versus 79%; P = 0.005) and delayed phases (days 2-5; 74% versus 63%; P = 0.004), as were rates of no vomiting (overall 77% versus 62%, P £ 0.001; acute 89% versus 81%, P = 0.004; delayed 79% versus 64%, P £ 0.001). Rates of no rescue therapy were similar between groups. Conclusions: Compared with an antiemetic regimen in which ondansetron + dexamethasone were given for 4 days, the aprepitant regimen was superior in the acute, delayed and overall phases of chemotherapy-induced nausea and vomiting. The aprepitant regimen should be considered a new standard of antiemetic therapy for cisplatin-treated patients. www.ClinicalTrials.gov Identifier: NTC0009020