Apomorphine to Uprima: the development of a practical erectogenic drug: a personal perspective. (1/25)

The development process for apomorphine SL as an effective treatment for patients with erectile dysfunction has been somewhat unusual. As often is the case, much of the impetus for the basic research originated in academia. However, somewhat unusually, the impetus for early stage clinical research also lay in the hands of the academics. This article represents a historical perspective from one of those involved throughout.  (+info)

Update on intravenous tissue plasminogen activator for acute stroke: from clinical trials to clinical practice. (2/25)

Tissue plasminogen activator (tPA) injected intravenously within 3 hours of symptom onset has emerged as a treatment option for acute ischemic stroke. Although controversial and not universally accepted, its use in carefully selected patients is supported by evidence from randomized controlled trials and by mounting community experience. In this paper we review the literature published in the past 5 years regarding the safety, clinical trial efficacy and real-world effectiveness of intravenous tPA for stroke. First we review data from the phase III clinical trials on which approval for tPA is based. Then we summarize a growing literature of postmarketing phase IV studies and discuss the limitations and challenges that lie ahead. Our aim is to provide clinicians with an overview of this evolving therapy.  (+info)

Cardiovascular thrombotic events in controlled, clinical trials of rofecoxib. (3/25)

BACKGROUND: In comparing aspirin, nonselective nonsteroidal antiinflammatory agents (NSAIDs), and cyclooxygenase (COX)-2 inhibitors, variation in platelet inhibitory effects exists that may be associated with differential risks of cardiovascular (CV) thrombotic events. Among the randomized, controlled trials with the COX-2 inhibitor rofecoxib, one study demonstrated a significant difference between rofecoxib and its NSAID comparator (naproxen) in the risk of CV thrombotic events. A combined analysis of individual patient data was undertaken to determine whether there was an excess of CV thrombotic events in patients treated with rofecoxib compared with those treated with placebo or nonselective NSAIDs. METHODS AND RESULTS: CV thrombotic events were assessed across 23 phase IIb to V rofecoxib studies. Comparisons were made between patients taking rofecoxib and those taking either placebo, naproxen (an NSAID with near-complete inhibition of platelet function throughout its dosing interval), or another nonselective NSAIDs used in the development program (diclofenac, ibuprofen, and nabumetone). The major outcome measure was the combined end point used by the Antiplatelet Trialists' Collaboration, which includes CV, hemorrhagic, and unknown deaths; nonfatal myocardial infarctions; and nonfatal strokes. More than 28 000 patients, representing >14 000 patient-years at risk, were analyzed. The relative risk for an end point was 0.84 (95% CI: 0.51, 1.38) when comparing rofecoxib with placebo; 0.79 (95% CI: 0.40, 1.55) when comparing rofecoxib with non-naproxen NSAIDs; and 1.69 (95% CI: 1.07, 2.69) when comparing rofecoxib with naproxen. CONCLUSIONS: This analysis provides no evidence for an excess of CV events for rofecoxib relative to either placebo or the non-naproxen NSAIDs that were studied. Differences observed between rofecoxib and naproxen are likely the result of the antiplatelet effects of the latter agent.  (+info)

Clinical data gap between phase III clinical trials (pre-marketing) and phase IV (post-marketing) studies: evaluation of etanercept in rheumatoid arthritis. (4/25)

BACKGROUND: There are fundamental differences in design between phase III clinical trials and phase IV post-marketing studies that involve patient characteristics, the clinical setting (environment) and the manner of drug use. As well, many phase IV studies are extensions of randomized clinical trials (RCTs) and suffer from selection bias. OBJECTIVE: To determine if the data obtained from RCTs of etanercept (Enbrel) in the treatment of rheumatoid arthritis would be representative of the effects attainable in community practice. METHOD: An analysis was conducted comparing data from published RCTs of etanercept use in rheumatoid arthritis patients with data collected in a community based cohort study that was not an extension of an RCT. RESULTS: Baseline clinical data, such as tender or painful joint count, patient's global assessment, the heath assessment questionnaire, physical and mental component summary of the SF-36, and rheumatoid arthritis drug profile were significantly different between the patients receiving etanercept in the phase IV community cohort study and the patients enrolled in the RCTs. Differences in the baseline data for the control patients were also noted amongst the RCT studies. The treatment outcome, American College of Rheumatology (ACR) response rate of 20%, 50% and 70% at 6 month, was the same between the cohort study and the RCTs, but at 12 months the clinical response was less for the community based patients than for the RCT patients. At 6 months there were fewer withdrawals involving community-based patients than RCT patients due to less frequent withdrawals associated with lack of efficacy. At 12 months the withdrawal rate due to either a lack of efficacy or from adverse events was similar between data sets. CONCLUSION: The data from the etanercept phase III RCTs may not reflect the characteristics of patients using etanercept in community practice, nor the clinical outcomes observed by RA patients at 12 months. These discrepancies may be derived from methodological differences in study design and patient selection. On the other hand, outcomes such as withdrawal rates at 12 months appear comparable between the two types of populations.  (+info)

Clinical and bacteriologic efficacy of telithromycin in patients with bacteremic community-acquired pneumonia. (5/25)

This retrospective analysis was performed to determine the clinical and bacteriologic efficacy of the ketolide antibacterial telithromycin in patients with community-acquired pneumonia (CAP) with pneumococcal bacteremia. Patients 13 years old with radiologically confirmed CAP and a positive blood culture for Streptococcus pneumoniae at screening were analyzed from eight multicenter Phase III/IV clinical trials. In four open-label, non-comparative studies, patients received telithromycin 800 mg once daily for 7-10 days. In four randomized, controlled, double-blind, comparative studies, patients received telithromycin 800 mg once daily for 5-10 days or a comparator antimicrobial (amoxicillin 1000 mg three times daily, clarithromycin 500 mg twice daily, or trovafloxacin 200 mg once daily) for 7-10 days. In total, 118 patients (telithromycin, 94/1061 [8.9%]; comparator, 24/244 [9.8%]) had documented pneumococcal bacteremia. Those who were treated with telithromycin achieved a clinical cure rate of 90.2% (74/82, per-protocol population); S. pneumoniae was eradicated in 77/82 (93.9%) bacteremic patients who received telithromycin and 15/19 (78.9%) comparator-treated patients. Clinical cure was also observed among telithromycin-treated bacteremic patients who were infected with penicillin- or erythromycin-resistant strains of S. pneumoniae (5/7 and 8/10, respectively). In conclusion, telithromycin achieves high clinical and bacteriologic cure rates in CAP patients with pneumococcal bacteremia.  (+info)

Assessing the relationship between antigenicity and immunogenicity of human rabies vaccines. Results of a meta-analysis. (6/25)

A meta-analysis was done to study the relationship between antigenecity and immunogenecity of human rabies vaccines. The data of ten cell culture human rabies vaccine studies conducted at a single centre during 1993-2004 were used in the study. The vaccines studied included Purified Chick Embryo Cell Vaccine (Kaketsuken, Japan and Rabipur, India), Purified Vero cell Rabies Vaccine (Verorab, France), Human Diploid Cell Vaccine (MIRV, France and Rabivax, Adsorbed and Lyophilized, India) and Rhesus Diploid Rabies Vaccine (adsorbed, USA). Interestingly, it was revealed that an higher antigenecity of rabies vaccines viz. potency of > or = 5 IU per single intramuscular dose did not result in significantly higher immunogenecity, as measured by rabies virus neutralizing antibody (RVNA) titers in the vaccinees, both on day 14 (t = 0.42, p > 0.66, GMR = 1.06, 95% CI of GMR = 0.82, 1.37) and day 90 (t = 0.80, p > 0.43, GMR = 1.15, 95% CI of GMR = 0.74, 1.14). However, as there are no reports of meta-analysis of cell culture human rabies vaccine trials, to confirm this observation the authors recommend further studies in this regard.  (+info)

Ezetimibe added to statin therapy (EASY study) - an evaluation by Australian general practitioners. (7/25)

BACKGROUND: This study estimated changes in low density lipoprotein cholesterol (LDL-C) levels and proportion of patients attaining goal LDL-C <2.5 mmol/L when ezetimibe was added to existing statin monotherapy under Pharmaceutical Benefits Scheme (PBS) guidelines in a general practice setting. METHODS: Target patients were those with coronary heart disease or diabetes mellitus eligible to receive ezetimibe under PBS guidelines. They were treated with ezetimibe 10 mg/day in addition to existing statin therapy for 6 weeks. RESULTS: One hundred and thirty patients received treatment, but for effectiveness we derived a per protocol subpopulation of 95. Low density lipoprotein cholesterol was reduced by 29% (95% confidence limits, 25-34% reduction), and goal LDL-C <2.5 mmol/L was reached in 70% of patients (95% confidence limits, 59-79%). Six patients were withdrawn because of adverse events. DISCUSSION: Changes in LDL-C and goal attainment in Australian general practice with the use of ezetimibe added to a statin were highly consistent with the findings from controlled clinical trials.  (+info)

Clinical trials in severe sepsis with drotrecogin alfa (activated). (8/25)

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