Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial.

BACKGROUND: Prophylaxis for venous thromboembolism is recommended for at least 10 days after total knee arthroplasty; oral regimens could enable shorter hospital stays. We aimed to test the efficacy and safety of oral rivaroxaban for the prevention of venous thromboembolism after total knee arthroplasty. METHODS: In a randomised, double-blind, phase III study, 3148 patients undergoing knee arthroplasty received either oral rivaroxaban 10 mg once daily, beginning 6-8 h after surgery, or subcutaneous enoxaparin 30 mg every 12 h, starting 12-24 h after surgery. Patients had mandatory bilateral venography between days 11 and 15. The primary efficacy outcome was the composite of any deep-vein thrombosis, non-fatal pulmonary embolism, or death from any cause up to day 17 after surgery. Efficacy was assessed as non-inferiority of rivaroxaban compared with enoxaparin in the per-protocol population (absolute non-inferiority limit -4%); if non-inferiority was shown, we assessed whether rivaroxaban had superior efficacy in the modified intention-to-treat population. The primary safety outcome was major bleeding. This trial is registered with ClinicalTrials.gov, number NCT00362232. FINDINGS: The primary efficacy outcome occurred in 67 (6.9%) of 965 patients given rivaroxaban and in 97 (10.1%) of 959 given enoxaparin (absolute risk reduction 3.19%, 95% CI 0.71-5.67; p=0.0118). Ten (0.7%) of 1526 patients given rivaroxaban and four (0.3%) of 1508 given enoxaparin had major bleeding (p=0.1096). INTERPRETATION: Oral rivaroxaban 10 mg once daily for 10-14 days was significantly superior to subcutaneous enoxaparin 30 mg given every 12 h for the prevention of venous thromboembolism after total knee arthroplasty. FUNDING: Bayer Schering Pharma AG, Johnson & Johnson Pharmaceutical Research & Development.

Safety, tolerability, pharmacokinetics, and efficacy of an interleukin-2 agonist among HIV-infected patients receiving highly active antiretroviral therapy.

We sought to determine the safety, maximum tolerated dose, optimal dose, and preliminary dose efficacy of intermittent subcutaneously (s.c.) administered BAY 50-4798 among patients with HIV infection receiving highly active antiretroviral therapy (HAART) compared with patients receiving HAART alone. A phase I/II randomized, double-blind, dose-escalation study was conducted of the safety, tolerability, pharmacokinetics, and efficacy of s.c. BAY 50-4798 administered to HIV-infected patients already receiving stable HAART. There were no unexpected safety findings in a population of HIV-infected patients receiving HAART plus SC BAY 50-4798 as adjunctive therapy. BAY 50-4798 exhibited nearly dose-proportional pharmacokinetics, and accumulation was minimal during multiple-dose treatment. Limited efficacy data indicated that treatment with BAY 50-4798 caused at least a transient increase in CD4(+) T cell counts in some recipients, particularly at the early time points. In general, this effect appeared to increase with increasing dose. Bay 50-4798 was generally well tolerated across the dose range tested, but a lack of potent, sustained immunologic activity suggests that further optimization of dose and schedule will be necessary.

Eradication of common pathogens at days 2, 3 and 4 of moxifloxacin therapy in patients with acute bacterial sinusitis.

BACKGROUND: Acute bacterial sinusitis (ABS) is a common infection in clinical practice. Data on time to bacteriologic eradication after antimicrobial therapy are lacking for most agents, but are necessary in order to optimize therapy. This was a prospective, single-arm, open-label, multicenter study to determine the time to bacteriologic eradication in ABS patients (maxillary sinusitis) treated with moxifloxacin. METHODS: Adult patients with radiologically and clinically confirmed ABS received once-daily moxifloxacin 400 mg for 10 days. Middle meatus secretion sampling was performed using nasal endoscopy pre-therapy, and repeated on 3 consecutive days during treatment. Target enrollment was 30 bacteriologically evaluable patients (pre-therapy culture positive for Streptococcus pneumoniae, Haemophilus influenzae or Moraxella catarrhalis and evaluable cultures for at least Day 2 and Day 3 during therapy visits), including at least 10 each with S. pneumoniae or H. influenzae. RESULTS: Of 192 patients enrolled, 42 were bacteriologically evaluable, with 48 pathogens isolated. Moxifloxacin was started on Day 1. Baseline bacteria were eradicated in 35/42 (83.3%) patients by day 2, 42/42 (100%) patients by day 3, and 41/42 (97.6%) patients by day 4. In terms of individual pathogens, 12/18 S. pneumoniae, 22/23 H. influenzae and 7/7 M. catarrhalis were eradicated by day 2 (total 41/48; 85.4%), and 18/18 S. pneumoniae and 23/23 H. influenzae were eradicated by day 3. On Day 4, S. pneumoniae was isolated from a patient who had negative cultures on Days 2 and 3. Thus, the Day 4 eradication rate was 47/48 (97.9%). Clinical success was achieved in 36/38 (94.7%) patients at the test of cure visit. CONCLUSION: In patients with ABS (maxillary sinusitis), moxifloxacin 400 mg once daily for 10 days resulted in eradication of baseline bacteria in 83.3% of patients by Day 2, 100% by Day 3 and 97.6% by Day 4.

Safety and tolerability of acarbose in the treatment of type 1 and type 2 diabetes mellitus.

OBJECTIVE: To assess the safety profile of acarbose treatment over a 1-year period at a dose range of 50-300mg three times daily in patients with type 1 or type 2 diabetes mellitus. STUDY DESIGN AND PATIENTS: In this 56-week, double-blind, parallel-group, multicentre comparison, patients were randomised to acarbose or placebo in a 2 : 1 ratio. An 8-week forced titration phase (from 50-300mg three times daily) was followed by a 48-week maintenance phase during which patients received the highest dose tolerated during titration. Patients were assessed at 13 visits with respect to adverse events/intercurrent illnesses, abnormal laboratory values (serum chemistry, urinalysis, complete blood and reticulocyte count, serum iron and total iron binding capacity, and serum vitamin B(6), B(12), D and folate levels), discontinuation rates, ECG findings, vital signs and evaluation of the patients' diaries with regard to gastrointestinal events. A total of 359 patients (acarbose 240, placebo 119) were valid for analysis; 21% had type 1 diabetes. Most patients received concomitant insulin or sulfonylurea treatment. RESULTS: Study withdrawal was reported for 35% of acarbose and 24% of placebo recipients (p = 0.053); adverse events were the main reason for withdrawal in acarbose recipients (20%; placebo group 5%; p < 0.01). The most common adverse events for acarbose recipients were gastrointestinal (abdominal pain, flatulence and diarrhoea), which were more frequent than in placebo patients (p < 0.01). These events occurred more often early in the study and attenuated over time. CONCLUSION: Acarbose was safe and well tolerated by the majority of diabetic patients over a 1-year treatment period.