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Placebo

About: Placebo is a(n) research topic. Over the lifetime, 43021 publication(s) have been published within this topic receiving 2587395 citation(s). The topic is also known as: placebo effect & placebos.
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Journal ArticleDOI
19 Aug 1998-JAMA
TL;DR: Treatment with oral conjugated equine estrogen plus medroxyprogesterone acetate did not reduce the overall rate of CHD events in postmenopausal women with established coronary disease and the treatment did increase the rate of thromboembolic events and gallbladder disease.
Abstract: Context.—Observational studies have found lower rates of coronary heart disease (CHD) in postmenopausal women who take estrogen than in women who do not, but this potential benefit has not been confirmed in clinical trials.Objective.—To determine if estrogen plus progestin therapy alters the risk for CHD events in postmenopausal women with established coronary disease.Design.—Randomized, blinded, placebo-controlled secondary prevention trial.Setting.—Outpatient and community settings at 20 US clinical centers.Participants.—A total of 2763 women with coronary disease, younger than 80 years, and postmenopausal with an intact uterus. Mean age was 66.7 years.Intervention.—Either 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate in 1 tablet daily (n=1380) or a placebo of identical appearance (n=1383). Follow-up averaged 4.1 years; 82% of those assigned to hormone treatment were taking it at the end of 1 year, and 75% at the end of 3 years.Main Outcome Measures.—The primary outcome was the occurrence of nonfatal myocardial infarction (MI) or CHD death. Secondary cardiovascular outcomes included coronary revascularization, unstable angina, congestive heart failure, resuscitated cardiac arrest, stroke or transient ischemic attack, and peripheral arterial disease. All-cause mortality was also considered.Results.—Overall, there were no significant differences between groups in the primary outcome or in any of the secondary cardiovascular outcomes: 172 women in the hormone group and 176 women in the placebo group had MI or CHD death (relative hazard [RH], 0.99; 95% confidence interval [CI], 0.80-1.22). The lack of an overall effect occurred despite a net 11% lower low-density lipoprotein cholesterol level and 10% higher high-density lipoprotein cholesterol level in the hormone group compared with the placebo group (each P<.001). Within the overall null effect, there was a statistically significant time trend, with more CHD events in the hormone group than in the placebo group in year 1 and fewer in years 4 and 5. More women in the hormone group than in the placebo group experienced venous thromboembolic events (34 vs 12; RH, 2.89; 95% CI, 1.50-5.58) and gallbladder disease (84 vs 62; RH, 1.38; 95% CI, 1.00-1.92). There were no significant differences in several other end points for which power was limited, including fracture, cancer, and total mortality (131 vs 123 deaths; RH, 1.08; 95% CI, 0.84-1.38).Conclusions.—During an average follow-up of 4.1 years, treatment with oral conjugated equine estrogen plus medroxyprogesterone acetate did not reduce the overall rate of CHD events in postmenopausal women with established coronary disease. The treatment did increase the rate of thromboembolic events and gallbladder disease. Based on the finding of no overall cardiovascular benefit and a pattern of early increase in risk of CHD events, we do not recommend starting this treatment for the purpose of secondary prevention of CHD. However, given the favorable pattern of CHD events after several years of therapy, it could be appropriate for women already receiving this treatment to continue.

5,896 citations


Journal ArticleDOI
TL;DR: As compared with placebo, intravenous alteplase administered between 3 and 4.5 hours after the onset of symptoms significantly improved clinical outcomes in patients with acute ischemic stroke; altePlase was more frequently associated with symptomatic intracranial hemorrhage.
Abstract: Background Intravenous thrombolysis with alteplase is the only approved treatment for acute ischemic stroke, but its efficacy and safety when administered more than 3 hours after the onset of symptoms have not been established. We tested the efficacy and safety of alteplase administered between 3 and 4.5 hours after the onset of a stroke. Methods After exclusion of patients with a brain hemorrhage or major infarction, as detected on a computed tomographic scan, we randomly assigned patients with acute ischemic stroke in a 1:1 double-blind fashion to receive treatment with intravenous alteplase (0.9 mg per kilogram of body weight) or placebo. The primary end point was disability at 90 days, dichotomized as a favorable outcome (a score of 0 or 1 on the modified Rankin scale, which has a range of 0 to 6, with 0 indicating no symptoms at all and 6 indicating death) or an unfavorable outcome (a score of 2 to 6 on the modified Rankin scale). The secondary end point was a global outcome analysis of four neurologic and disability scores combined. Safety end points included death, symptomatic intracranial hemorrhage, and other serious adverse events. Results We enrolled a total of 821 patients in the study and randomly assigned 418 to the alteplase group and 403 to the placebo group. The median time for the administration of alteplase was 3 hours 59 minutes. More patients had a favorable outcome with alte plase than with placebo (52.4% vs. 45.2%; odds ratio, 1.34; 95% confidence interval [CI], 1.02 to 1.76; P = 0.04). In the global analysis, the outcome was also improved with alteplase as compared with placebo (odds ratio, 1.28; 95% CI, 1.00 to 1.65; P<0.05). The incidence of intracranial hemorrhage was higher with alteplase than with placebo (for any intracranial hemorrhage, 27.0% vs. 17.6%; P = 0.001; for symptomatic intracranial hemorrhage, 2.4% vs. 0.2%; P = 0.008). Mortality did not differ significant ly between the alteplase and placebo groups (7.7% and 8.4%, respectively; P = 0.68). There was no significant difference in the rate of other serious adverse events. Conclusions As compared with placebo, intravenous alteplase administered between 3 and 4.5 hours after the onset of symptoms significantly improved clinical outcomes in patients with acute ischemic stroke; alteplase was more frequently associated with symptomatic intracranial hemorrhage. (ClinicalTrials.gov number, NCT00153036.)

4,913 citations


Journal ArticleDOI
TL;DR: As compared with placebo, treatment with sorafenib prolongs progression-free survival in patients with advanced clear-cell renal-cell carcinoma in whom previous therapy has failed; however, treatment is associated with increased toxic effects.
Abstract: Background We conducted a phase 3, randomized, double-blind, placebo-controlled trial of sorafenib, a multikinase inhibitor of tumor-cell proliferation and angiogenesis, in patients with advanced clear-cell renal-cell carcinoma. Methods From November 2003 to March 2005, we randomly assigned 903 patients with renal-cell carcinoma that was resistant to standard therapy to receive either continuous treatment with oral sorafenib (at a dose of 400 mg twice daily) or placebo; 451 patients received sorafenib and 452 received placebo. The primary end point was overall survival. A single planned analysis of progression-free survival in January 2005 showed a statistically significant benefit of sorafenib over placebo. Consequently, crossover was permitted from placebo to sorafenib, beginning in May 2005. Results At the January 2005 cutoff, the median progression-free survival was 5.5 months in the sorafenib group and 2.8 months in the placebo group (hazard ratio for disease progression in the sorafenib group, 0.44;...

4,400 citations


Journal ArticleDOI
TL;DR: The use of sipuleucel-T prolonged overall survival among men with metastatic castration-resistant prostate cancer and immune responses to the immunizing antigen were observed in patients who received sipuleUcel- T.
Abstract: Background Sipuleucel-T, an autologous active cellular immunotherapy, has shown evidence of efficacy in reducing the risk of death among men with metastatic castration-resistant prostate cancer. Methods In this double-blind, placebo-controlled, multicenter phase 3 trial, we randomly assigned 512 patients in a 2:1 ratio to receive either sipuleucel-T (341 patients) or placebo (171 patients) administered intravenously every 2 weeks, for a total of three infusions. The primary end point was overall survival, analyzed by means of a stratified Cox regression model adjusted for baseline levels of serum prostate-specific antigen (PSA) and lactate dehydrogenase. Results In the sipuleucel-T group, there was a relative reduction of 22% in the risk of death as compared with the placebo group (hazard ratio, 0.78; 95% confidence interval [CI], 0.61 to 0.98; P = 0.03). This reduction represented a 4.1-month improvement in median survival (25.8 months in the sipuleucel-T group vs. 21.7 months in the placebo group). The 36-month survival probability was 31.7% in the sipuleucel-T group versus 23.0% in the placebo group. The treatment effect was also observed with the use of an unadjusted Cox model and a log-rank test (hazard ratio, 0.77; 95% CI, 0.61 to 0.97; P = 0.02) and after adjustment for use of docetaxel after the study therapy (hazard ratio, 0.78; 95% CI, 0.62 to 0.98; P = 0.03). The time to objective disease progression was similar in the two study groups. Immune responses to the immunizing antigen were observed in patients who received sipuleucel-T. Adverse events that were more frequently reported in the sipuleucel-T group than in the placebo group included chills, fever, and headache. Conclusions The use of sipuleucel-T prolonged overall survival among men with metastatic castration-resistant prostate cancer. No effect on the time to disease progression was observed. (Funded by Dendreon; ClinicalTrials.gov number, NCT00065442.)

4,366 citations


Journal ArticleDOI
02 Jan 1999-The Lancet
TL;DR: Beta-blocker therapy had benefits for survival in stable heart-failure patients and should not be extrapolated to patients with severe class IV symptoms and recent instability because safety and efficacy has not been established in these patients.
Abstract: Summary Background In patients with heart failure, β-blockade has improved morbidity and left-ventricular function, but the impact on survival is uncertain. We investigated the efficacy of bisoprolol, a β, selective adrenoceptor blocker in decreasing all-cause mortality in chronic heart failure. Methods In a multicentre double-blind randomised placebo-controlled trial in Europe, we enrolled 2647 symptomatic patients in New York Heart Association class III or IV, with left-ventricular ejection fraction of 35% or less receiving standard therapy with diuretics and inhibitors of angiotensin-converting enzyme. We randomly assigned patients bisoprolol 1·25 mg (n=1327) or placebo (n=1320) daily, the drug being progressively increased to a maximum of 10 mg per day. Patients were followed up for a mean of 1·3 years. Analysis was by intention to treat. Findings CIBIS-II was stopped early, after the second interim analysis, because bisoprolol showed a significant mortality benefit. All-cause mortality was significantly lower with bisoprolol than on placebo (156 [11·8%] vs 228 [17·3%] deaths with a hazard ratio of 0·66 (95% CI 0·54–0·81, p vs 83 [6·3%] deaths), with a hazard ratio of 0·56 (0·39–0·80, p=0·0011). Treatment effects were independent of the severity or cause of heart failure. Interpretation β-blocker therapy had benefits for survival in stable heart-failure patients. Results should not, however, be extrapolated to patients with severe class IV symptoms and recent instability because safety and efficacy has not been established in these patients.

4,094 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202210
20212,220
20201,987
20191,752
20181,730
20171,935

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Topic's top 5 most impactful authors

R Andrew Moore

102 papers, 10.5K citations

Shahin Akhondzadeh

98 papers, 4.8K citations

Ted J. Kaptchuk

85 papers, 8.1K citations

Fabrizio Benedetti

85 papers, 9.5K citations

Maurizio Fava

85 papers, 4.5K citations