Clinical and bacteriological efficacy and safety of 5 and 7 day regimens of telithromycin once daily compared with a 10 day regimen of clarithromycin twice daily in patients with mild to moderate community-acquired pneumonia

OBJECTIVES: This study was conducted to investigate the potential equivalence in clinical efficacy and assess safety of a 5 or 7 day regimen of oral telithromycin (800 mg once daily) and a 10 day regimen of oral clarithromycin (500 mg twice daily) in treating community-acquired pneumonia (CAP). Bacteriological efficacy was also compared. METHODS: This was a multicentre, randomized, double-blind, active-controlled study. Patients with mild to moderate CAP received telithromycin 800 mg once a day for 5 (n=193) or 7 (n=195) days or clarithromycin 500 mg twice a day for 10 days (n=187). In these groups, 159, 161 and 146 patients, respectively, completed the study. RESULTS: At the post-therapy/test-of-cure evaluation, clinical cure rates (per-protocol clinical population) were 89.3% (5 days) and 88.8% (7 days) for telithromycin, and 91.8% for clarithromycin 10 days. Satisfactory bacteriological outcome rates (per-protocol bacteriological population) were 87.7% and 80.0% for 5 and 7 days of telithromycin, respectively, and 83.3% for 10 days of clarithromycin. Bacteriological eradication rates in the respective treatment groups were, for Streptococcus pneumoniae, 95.8% (23/24), 96.7% (29/30) and 88.5% (23/26); for Haemophilus influenzae, 88.0% (22/25), 84.0% (21/25) and 88.2% (15/17) and for Moraxella catarrhalis, 1/1, 4/5 and 3/4. Both telithromycin regimens demonstrated clinical efficacy against pneumococcal bacteraemia (19/19), atypical pathogens (9/9) and erythromycin-resistant S. pneumoniae isolates (5/5). Most treatment-emergent adverse events were mild to moderate in intensity with most commonly reported adverse events involving the gastrointestinal system. CONCLUSIONS: Telithromycin 800 mg administered once a day for 5 or 7 days was as effective and safe as clarithromycin 500 mg administered twice a day for 10 days in treating patients with CAP caused by common respiratory pathogens, including macrolide-resistant isolates, and pneumococcal bacteraemia.     

Clinical efficacy and safety of telmisartan 80 mg once daily compared with enalapril 20 mg once daily in patients with mild-to-moderate hypertension: results of a multicentre study

The efficacy and safety of once-daily telmisartan 80 mg vs. once-daily enalapril 20 mg in the treatment of essential hypertension were evaluated in a multicentre, single-blind, placebo-controlled, randomised trial. In total, 68 patients (49 females, 19 males) with mild-to-moderate hypertension, defined as morning supine systolic blood pressure (SBP) 141-149 mmHg, diastolic blood pressure (DBP) 95-114 mmHg, were enrolled. After a 4-week placebo run-in phase, patients were randomly assigned to treatment with telmisartan or enalapril administered once daily in the morning for 8 weeks. No statistically significant differences were found in the baseline characteristics of patients in either group. Both SBP and DBP were decreased in both treatment groups, but the reductions were statistically different in favour of telmisartan (SBP, p = 0.013; DBP, p = 0.002). The incidence of adverse effects was lower in the telmisartan group, with the absence of cough. In conclusion, telmisartan is more effective and better tolerated than enalapril for the treatment of hypertension and has the advantage that it does not cause cough.     

Clinical efficacy and safety of telmisartan 80 mg once daily vs. atenolol 50 mg once daily in patients with mild-to-moderate hypertension

The objective of this open-label, parallel-group comparative study was to assess the clinical efficacy and safety of once-daily treatment for 8 weeks with telmisartan 80 mg in comparison with atenolol 50 mg on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in patients with mild-to-moderate hypertension (morning supine SBP 141-199 mmHg, DBP 95-114 mmHg). A total of 58 patients were enrolled. The comparability of the two treatment groups was statistically documented at the beginning of the study. Telmisartan was more effective than atenolol, with a decrease in SBP of 21.7 mmHg vs. 11.8 mmHg (p = 0.03) and a non-significant decrease in DBP of 14.7 mmHg vs. 10.1 mmHg. The safety profiles of both drugs were very similar; both drugs were well tolerated. In conclusion, once-daily telmisartan 80 mg is more effective than once-daily atenolol 50 mg in lowering SBP with no negative chronotropism. Furthermore, telmisartan was as well tolerated as atenolol in the treatment of mild-to-moderate essential hypertension in adults.     

Efficacy and safety of glimepiride/metformin sustained release once daily vs. glimepiride/metformin twice daily in patients with type 2 diabetes

Aims: The study investigated the clinical equivalence in reducing haemoglobin A1c (A1C) between glimepiride/metformin sustained release (GM‐SR) 2/500 mg, a fixed‐dose combination, once daily and glimepiride/metformin (GM) 1/250 mg, a fixed‐dose combination, twice daily in patients with type 2 diabetes (T2D). Methods: A multicentre, randomised, double‐blind, double‐dummy study was conducted in 14 hospitals in Korea. Inclusion criteria were age 30–75 years, T2D diagnosis no longer than 10 years previously, A1C between 7% and 10%, and body mass index < 40 kg/m². A total of 207 subjects were randomised into the GM‐SR group (n = 101) or the GM group (n = 106). Participants were assessed at baseline, 8 weeks and 16 weeks after treatment. Results: After 16 weeks treatment, no difference in baseline‐adjusted changes of A1C (primary efficacy variable) was observed between the two groups (?0.59% for GM‐SR group vs. ?0.61% for GM group, 95% CI: ?0.17 to 0.21; p = 0.84). In addition, there were no significant differences in secondary efficacy parameters between the two groups, including changes in A1C up to week 8, changes in fasting plasma glucose (FPG) and 2‐h‐postprandial plasma glucose up to week 8 and week 16, response rate, drug compliance and hypoglycaemic events. However, there was a difference in baseline‐adjusted changes of FPG between the two groups (?1.01 mmol/l for GM‐SR group vs. ?1.52 mmol/l for GM group, p = 0.01 in the intention to treat set). Conclusions: GM‐SR 2/500 mg once daily was as effective as GM 1/250 mg twice daily in lowering A1C. In addition, no difference was noted in hypoglycaemic events between the two groups.     

Efficacy and safety of rosuvastatin alone and in combination with cholestyramine in patients with severe hypercholesterolemia: a randomized, open-label, multicenter trial

BACKGROUND: Patients with severe hypercholesterolemia may need greater cholesterol reductions than can be achieved with statin therapy alone. OBJECTIVE: The primary objective of this trial was to compare the efficacy of a combination of rosuvastatin plus cholestyramine with that of rosuvastatin alone for reducing low-density lipoprotein cholesterol (LDL-C) levels after 6 weeks of treatment. METHODS: In this open-label, multicenter, randomized, parallel-group, comparator trial, adult patients with severe hypercholesterolemia (LDL-C level, 190-400 mg/dL) received rosuvastatin 40 mg/d for 6 weeks after a 6-week dietary lead-in period and were then randomized to 6 weeks of treatment with rosuvastatin 80 mg/d alone or rosuvastatin 80 mg/d plus cholestyramine 16 g/d (8 g BID with meals). RESULTS: Of 153 eligible patients, 147 (83 men, 64 women; mean [SD] age, 54.5 [13.7] years; mean [SD] bodyweight, 81.3 [14.4] kg) received randomized treatment, and 144 had post baseline measurements and were included in the analysis. The mean (SD) reduction in LDL-C was 522% (13.0%) after treatment with rosuvastatin 40 mg, and the least squares mean (SE) reductions in LDL-C were 56.4% (1.8%) and 60.5% (1.8%) after treatment with rosuvastatin 80 mg alone (n = 69) and rosuvastatin 80 mg plus cholestyramine (n = 75), respectively. No significant differences between treatments were found for these or other lipid measurements. Incremental LDL-C reductions >30% were obtained in 29% (22/75) of patients receiving combination therapy and 4% (3/69) of patients receiving rosuvastatin alone. The combination therapy was less well tolerated, primarily due to gastrointestinal symptoms; otherwise, the treatments were generally well tolerated. CONCLUSION: In this group of patients with severe hypercholesterolemia, the combination of rosuvastatin 80 mg with cholestyramine 16 g/d did not provide a significantly greater efficacy benefit than rosuvastatin alone.     

A multicentric study of netilmicin once daily versus thrice daily in patients with appendicitis and other intra-abdominal infections

This multicentric, randomized, double-blind trial compared the efficacy and safety of netilmicin, 4.5 mg/kg od and 1.5 mg/kg tid, in patients with intra-abdominal infections. Of 114 patients enrolled, 57 patients (mean age 40.3 years) in the od group and 55 (mean age 36.8 years) in the tid group were evaluated for efficacy; 58 and 56 patients in corresponding groups were evaluated for safety. Among those evaluated for efficacy were 12 od-treated and 11 tid-treated patients with documented septicaemia, and 32 and 30 patients of respective groups with polymicrobial infections. Initially, 86 and 81 netilmicin-susceptible causative microorganisms were isolated in corresponding groups. Of these pathogens, 55% in the od group and 62% in the tid group were Escherichia coli. Daily dosage of netilmicin ranged from 3.70 to 4.71 mg/kg (mean 4.50) for the od group and from 3.06 to 4.76 mg/kg (mean 4.46) for the tid group. Duration of netilmicin therapy ranged from six to 13 days (mean 8.7 days) for od-treated patients and from seven to 16 days (mean 8.8 days) for tid-treated patients. Concomitant metronidazole was administered to 41 patients of the od group and 34 of the tid group; one patient in the tid group received clindamycin. Clinical and bacteriological responses were assessed, and peak and trough serum netilmicin levels were measured periodically, during therapy. Laboratory tests, including determinations of serum creatinine and blood urea nitrogen values, were performed throughout the trial. A clinical cure was achieved in 57/57 od-treated patients and 54/55 tid-treated patients; treatment failed in one tid-treated patient (1/55). In od and tid groups, 86/86 and 80/81 netilmicin-susceptible pathogens initially isolated were considered to be eliminated, respectively; one isolate (Esch. coli) persisted in the tid group. Mean peak serum netilmicin concentration in the od group was approximately two-fold greater than that in the tid group; mean trough serum netilmicin concentrations were similar for the two groups. Adverse reactions were limited to mild pain at the site of netilmicin administration in several patients in each treatment group. Netilmicin od and tid (alone or in combination with metronidazole) were similarly efficacious in the treatment of patients with appendicitis and other intra-abdominal infections caused by netilmicin-susceptible pathogens. Both dosage regimens of netilmicin were safe and well tolerated.     

Efficacy and safety of alfuzosin 10 mg once daily in the treatment of symptomatic benign prostatic hyperplasia

Benign prostatic hyperplasia (BPH) is a common disorder in ageing men. Patients with BPH often present with bothersome irritative and obstructive lower urinary tract symptoms -- urgency, frequency, nocturia, feeling of insufficient bladder emptying and weak or intermittent flow. alpha(1)-Blockers are the most frequently prescribed oral medications for the first-line treatment of the symptoms associated with BPH. Alfuzosin is a uroselective alpha(1)-blocker that relaxes the smooth muscle of the bladder neck and prostate gland to alleviate BPH symptoms. A pooled analysis of three phase III trials confirmed that treatment with alfuzosin 10 mg q.d. significantly improves the peak urinary flow rate and symptom severity compared with placebo treatment. Unlike some other alpha(1)-blockers, alfuzosin 10 mg q.d. is associated with a low incidence of sexual and vasodilatory side effects. Based on the clinical trials reviewed, alfuzosin 10 mg q.d. is an effective and well-tolerated treatment for the urinary symptoms associated with BPH.     

Efficacy and safety of pitavastatin in Japanese patients with hypercholesterolemia: LIVES study and subanalysis

The Livalo Effectiveness and Safety (LIVES) study was an observational study to examine the efficacy and safety of pitavastatin, a newly developed drug, in approximately 20,000 Japanese patients with hypercholesterolemia. During a 2-year follow-up period, no significant problems concerning safety were observed upon treatment with pitavastatin. Pitavastatin demonstrated potent and stable lowering of the LDL-cholesterol level. The LIVES study subanalyses revealed significant and continuous elevation of HDL-cholesterol in association with pitavastatin treatment and also showed that the drug did not adversely affect glycemic control as evaluated by the glycohemoglobin A_1c level. Moreover, pitavastatin treatment was associated with an increase in estimated glomerular filtration rate in subjects with chronic kidney disease. These results suggest the usefulness of pitavastatin in hypercholesterolemic patients from various backgrounds. The ongoing LIVES study extension is expected to provide further data on cardiovascular outcome in subjects treated with pitavastatin.     

Efficacy and safety of pitavastatin in Japanese patients with hypercholesterolemia: LIVES study and subanalysis

The Livalo Effectiveness and Safety (LIVES) study was an observational study to examine the efficacy and safety of pitavastatin, a newly developed drug, in approximately 20,000 Japanese patients with hypercholesterolemia. During a 2-year follow-up period, no significant problems concerning safety were observed upon treatment with pitavastatin. Pitavastatin demonstrated potent and stable lowering of the LDL-cholesterol level. The LIVES study subanalyses revealed significant and continuous elevation of HDL-cholesterol in association with pitavastatin treatment and also showed that the drug did not adversely affect glycemic control as evaluated by the glycohemoglobin A(1c) level. Moreover, pitavastatin treatment was associated with an increase in estimated glomerular filtration rate in subjects with chronic kidney disease. These results suggest the usefulness of pitavastatin in hypercholesterolemic patients from various backgrounds. The ongoing LIVES study extension is expected to provide further data on cardiovascular outcome in subjects treated with pitavastatin.     

Nitrendipine once daily compared with nicardipine in the treatment of mild to moderate hypertension

Twenty-four patients with mild to moderate hypertension were randomly assigned to 42 days of treatment with 20 mg of nitrendipine once daily or 20 mg of nicardipine thrice daily. In the nitrendipine-treated and nicardipine-treated patients, respectively, mean resting blood pressure decreased from 163 +/- 12 and 161 +/- 11 mmHg at baseline to 152 +/- 12 and 146 +/- 9 mmHg at six weeks (P less than 0.001). Blood pressures were reduced after one day of treatment, followed by an attenuation of the drug effect. In both treatment groups, blood pressures after cycloergometric, isometric, and cold-pressure tests were significantly lower at six weeks than at baseline; at six weeks, blood pressures were also significantly reduced two hours after drug administration, compared with those at or just before drug administration. It is concluded that nitrendipine taken once daily is safe and effective in the treatment of mild to moderate hypertension.     

Comparative efficacy of once versus twice daily mevinolin in the therapy of familial hypercholesterolemia

Mevinolin, a competitive inhibitor of the rate-limiting enzyme in cholesterol biosynthesis, is an effective hypocholesterolemic agent in patients with primary hypercholesterolemia when given in a twice-daily regimen. The present study compares the hypocholesterolemic effects of mevinolin given in a twice-daily dosage regimen with the same total dosage given either once in the morning or once in the evening in 12 patients with heterozygous familial hypercholesterolemia. Ten patients took a total daily dose of 40 mg of mevinolin and two took 20 mg. On the twice-daily dosage regimen, plasma concentrations of total cholesterol decreased 29.5% and 35.9% as compared with 21.4% and 26.9% with mevinolin given once in the morning and 27% and 32.2% with the drug given once in the evening. These values are all significantly different from baseline, but differences between the three treatment regimens do not reach statistical significance (P = 0.07 for the twice-daily versus once-in-the-morning dosage regimens). We conclude that once-daily administration of mevinolin, particularly in the evening, is an effective hypocholesterolemic regimen in patients with familial hypercholesterolemia.     

Efficacy and safety of once weekly subcutaneous idrabiotaparinux in the treatment of patients with symptomatic deep venous thrombosis

Summary. Background: Idraparinux, a long acting inhibitor of factor (F) Xa, is as effective as standard anticoagulant therapy for patients with symptomatic deep venous thrombosis. We investigated the potential use of the biotinylated molecule, idrabiotaparinux. Biotinylation enables reversal of the anticoagulant effect. Methods: We performed a randomized double‐blind trial in 757 patients with symptomatic deep venous thrombosis, comparing equimolar doses of idrabiotaparinux (3 mg) with idraparinux (2.5 mg), both given subcutaneously, once weekly for 6 months. Inhibition of FXa activity was measured at days 15, 36, 57, 92 and 183. The efficacy outcome was recurrent venous thromboembolism. The safety outcomes were clinically relevant bleeding and death. Results: Inhibition of FXa was similar in the two treatment groups at each time point of measurement. Recurrent venous thromboembolism during the 6‐month treatment period occurred in nine of 386 patients (2.3%) in the idrabiotaparinux group and in 12 of 371 patients (3.2%) in the idraparinux group, a difference of – 0.9% (95% confidence interval, ?3.2–1.4%). The incidence of clinically relevant bleeding was 5.2% in the idrabiotaparinux group and 7.3% in the idraparinux group (P = 0.29), a difference of – 2.1% (95% confidence interval, ?5.6–1.4%). Six patients (1.6%) who received idrabiotaparinux died, compared with 12 patients (3.2%) given idraparinux, a difference of – 1.7% (95% confidence interval, ?3.9–0.5%). Conclusions: Idrabiotaparinux has a similar time course of FXa inhibition, efficacy and safety to idraparinux for the treatment of deep venous thrombosis.     

Multi-centre double-blind comparison of terfenadine once daily versus twice daily in patients with hay fever

This double-blind, randomized multi-centre study was designed to compare efficacy and tolerability of 120 mg terfenadine taken once daily (in the morning) with the established regimen of 60 mg terfenadine taken twice daily in the treatment of seasonal rhinitis. Two comparable groups, a total of 191 hay fever patients, were treated for 1 week. Symptom severity was assessed by the investigators before and at the end of the treatment (visual analogue scale), and daily by the patient (four-point rating scale). All symptoms improved to a similar degree in both groups. Differences between the two groups were not statistically significant, except for nasal symptoms in three cases as assessed by the visual analogue scale in one centre (better relief in the group given 120 mg terfenadine once daily). Tolerability was good and similar in both groups. The data presented show that in the treatment of hay fever 120 mg terfenadine given once daily is an effective, convenient and well tolerated alternative to the regimen of 60 mg terfenadine given twice daily.     

Efficacy and safety of barnidipine compared with felodipine in the treatment of hypertension in Chinese patients

The efficacy and safety profiles of barnidipine in the treatment of hypertension were evaluated in an open parallel-group study. Fifty-nine Chinese patients with mild-to-moderate essential hypertension were randomized to receive either barnidipine or felodipine (5 mg once daily, titrated to 10 mg or 15 mg once daily, as indicated) for 12 weeks. Both drugs reduced blood pressures significantly with > or = 68% of cases obtaining marked or moderate blood pressure reduction. Mean reductions in systolic and diastolic blood pressure for barnidipine treatment were 23.7 +/- 13.5 mmHg and 12.7 +/- 7.9 mmHg, and for felodipine, 24.3 +/- 18.4 mmHg and 14.5 +/- 10.0 mmHg, respectively. There was no significant difference between these two drugs in anti-hypertensive effect, heart rate, laboratory measurements or incidence of adverse events. The only difference was that more patients taking felodipine experienced palpitations. We conclude that barnidipine has similar efficacy and a similar safety profile to felodipine in the treatment of mild-to-moderate essential hypertension in Chinese patients.     

A randomized, open-label study to evaluate the efficacy and safety of pitavastatin compared with simvastatin in Korean patients with hypercholesterolemia

BACKGROUND: Pitavastatin is a 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor used to treat hypercholesterolemia. OBJECTIVE: The goal of this study was to compare the efficacy and safety of pitavastatin versus those of simvastatin in Korean patients with hypercholesterolemia. METHODS: This was an 8-week, multicenter, prospective, randomized, open-label, Phase III clinical trial. Male and female Korean patients with hypercholesterolemia who were between the ages of 20 and 75 years and who had a fasting triglyceride level <600 mg/dL and a low-density lipoprotein (LDL) cholesterol level >130 mg/dL after a 4-week dietary lead-in period were eligible for entry. Eligible patients were randomized into 2 groups in a 1:1 ratio. Patients received pitavastatin 2 mg once daily or simvastatin 20 mg once daily for 8 weeks. The medication was administered initially for 4 weeks, and an additional 4 weeks of study medication was prescribed at week 4. The final visit was conducted 8 weeks after randomization. RESULTS: Of the 104 patients randomized to treatment, 95 patients (59 women; 36 men) completed the study (49 in the pitavastatin group [mean age, 59.9 years] and 46 in the simvastatin group [mean age, 56.4 years]). No significant difference was found between groups with respect to patient age, sex, or body mass index. There was no significant difference in the percent decrease in LDL cholesterol levels (mean [SD], 38.2% [11.6%] decrease for the pitavastatin group vs 39.4% [12.9%] decrease for the simvastatin group [P = 0.648]). Also, there were no significant differences between the 2 study groups in the percent changes in total cholesterol, triglyceride, or high-density lipoprotein (HDL) cholesterol levels from baseline to study end. No significant difference was observed for the proportion of patients who achieved the LDL cholesterol goal of the National Cholesterol Education Program Adult Treatment Panel III: 93.9% (46/49) of patients in the pitavastatin group and 91.3% (42/46) of patients in the simvastatin group (P = 0.709) met the target level. At least 1 clinical adverse event and at least 1 adverse drug reaction were observed in 25.0% (13/52) and 11.5% (6/52), respectively, of patients in the pitavastatin group, and 37.3% (19/51) and 23.5% (12/51), respectively, in the simvastatin group; this difference was not statistically significant. The most common adverse event was an elevation in creatine kinase levels >2 times the upper limit of normal in 3.8% of pitavastatin-treated patients and 9.8% of simvastatin-treated patients (P = 0.269). There were no serious adverse drug reactions observed in either group. CONCLUSION: The HMG-CoA reductase inhibitor pitavastatin was found to be noninferior to simvastatin in terms of reducing LDL cholesterol, total cholesterol, and triglyceride levels, and increasing HDL cholesterol levels, in Korean patients with hypercholesterolemia after 8 weeks of treatment.     

不同剂量瑞舒伐他汀对颈动脉粥样硬化合并高血脂患者疗效及安全性的对照分析

目的观察不同剂量瑞舒伐他汀治疗颈动脉粥样硬化合并高血脂患者的疗效及安全性,并进行对照分析。方法本研究选取2008年5月~2011年5月颈动脉粥样硬化合并高血脂患者110例,随机分为瑞舒伐他汀5 mg组(A组)、10 mg组(B组)、20mg组(C组),均为晚餐后顿服。比较3组患者治疗前后TC、TG、HDL-C、LDL-C、颈动脉斑块面积、颈内膜-中膜厚度的变化,并统计不良反应发生情况。结果 3组患者治疗后颈动脉斑块面积、颈内膜-中膜厚度均明显减小(P<0.01);TC、TG、LDL-C指标均明显降低(P<0.01),HDL-C明显增高(P<0.01)。但总体疗效C组优于B组;B组优于A组(P<0.05或P<0.01)。3组患者治疗前后均未发现明显不良反应。结论瑞舒伐他汀在治疗颈动脉粥样硬化合并高血脂患者方面疗效显著,具有良好的调脂,抗炎以及抗动脉硬化作用,其疗效具有一定的剂量依赖性,本研究3种剂量治疗均未发现严重不良反应,安全性值得认可。     

Efficacy and safety of ezetimibe coadministered with statins: randomised, placebo-controlled, blinded experience in 2382 patients with primary hypercholesterolemia

We assessed pooled safety and lipid-regulating efficacy data from four similarly designed trials of ezetimibe coadministered with statins in 2382 patients with primary hypercholesterolemia. Patients were randomised to one of the following double-blind treatments for 12 weeks: placebo; ezetimibe 10 mg; statin; or statin + ezetimibe. Statin doses tested were 10, 20, 40 mg/day (atorvastatin, simvastatin, pravastatin or lovastatin) or 80 mg/day (atorvastatin, simvastatin). Treatment with ezetimibe + statin led to significantly greater reductions in low-density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B and increases in HDL-C, compared to statin alone. At each statin dose, treatment with ezetimibe + statin led to a greater LDL-C reduction compared to the next highest statin monotherapy dose. Ezetimibe + statin had a safety profile similar to statin monotherapy. Coadministration of ezetimibe + statin offers a well-tolerated, highly efficacious new treatment strategy for patients with hypercholesterolemia.