Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PLACEBOS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 811 records · Page 45Linked to original sources
PubMed1999

Double-blind comparison of citalopram and placebo in depressed outpatients with melancholia.

This multicenter study compared the efficacy and safety of citalopram and placebo in a population of moderately to severely depressed patients with melancholia. This randomized, double-blind, parallel-group study compared citalopram (flexible dose; 20-80 mg/day) with placebo in 180 psychiatric outpatients with a DSM-III diagnosis of major depression or bipolar disorder, depressed, who also met DSM-III criteria for melancholia. Following a 1-week placebo washout period, patients meeting study entry criteria were randomized to 4 weeks of double-blind treatment with either citalopram or placebo. Efficacy measures included the Hamilton Rating Scale for Depression (HAM-D), the Clinical Global Impressions (CGI) Scale, and the Zung Self-Rating Depression Scale. Patients treated with citalopram showed significantly greater improvement at endpoint than placebo patients on the HAM-D, CGI, and Zung scales. On the HAM-D, citalopram patients exhibited significantly greater improvement than placebo patients after 1 week of double-blind treatment and at all subsequent study visits. Endpoint analyses of the HAM-D subscales demonstrated that citalopram produced significant improvement of the psychomotor retardation, cognitive disturbance, sleep disturbance, and melancholia symptom clusters. Nausea, dry mouth, somnolence, dizziness, and increased sweating were reported at higher rates by citalopram-treated patients than by placebo-treated patients, but there were no significant citalopram-placebo differences in the incidence of activation (e.g., anxiety, nervousness, insomnia) or sexual dysfunction. Analysis of electrocardiograms, vital signs, and laboratory tests did not reveal any clinically significant effects of citalopram treatment. The results of this study indicate that citalopram is safe and effective in the treatment of depressed patients with melancholia, and is associated with a favorable side effect profile and a potentially rapid onset of action.

Adult↗
PubMed2000

[Randomized placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients].

BACKGROUND: We undertook a randomised controlled trial to assess the efficacy and tolerance of orlistat, a gastrointestinal lipase inhibitor, in promoting weight loss and preventing weight regain in obese patients over a 2-year period. METHODS: 743 patients (body-mass index 28-47 kg/m2), recruited at 15 European centres, entered a 4-week, single-blind, placebo lead-in period on a slightly hypocaloric diet (600 kcal/day deficit). 688 patients who completed the lead-in were assigned double-blind treatment with orlistat 120 mg (three times a day) or placebo for 1 year in conjunction with the hypocaloric diet. In a second 52-week double-blind period patients were reassigned orlistat or placebo with a weight maintenance (eucaloric) diet. FINDINGS: From the start of lead-in to the end of year 1, the orlistat group lost, on average, more bodyweight than the placebo group (10.2% [10.3 kg] vs 6.1% [6.1 kg]; LSM difference 3.9 kg [p < 0.001] from randomisation to the end of year 1). During year 2, patients who continued with orlistat regained, on average, half as much weight as those patients switched to placebo (p < 0.001). Patients switched from placebo to orlistat lost an additional 0.9 kg during year 2, compared with a mean regain of 2.5 kg in patients who continued on placebo (p < 0.001). Total cholesterol, low-density lipoprotein (LDL) cholesterol, LDL/high-density lipoprotein ratio, and concentrations of glucose and insulin decreased more in the orlistat group than in the placebo group. Gastrointestinal adverse events were more common in the orlistat group. Other adverse symptoms occurred at a similar frequency during both treatments. INTERPRETATION: Orlistat taken with an appropriate diet promotes clinically significant weight loss and reduces weight regain in obese patients over a 2-year period. The use of orlistat beyond 2 years needs careful monitoring with respect to efficacy and adverse events.

Adolescent↗
PubMed1992

Factors influencing self-administration of, and subjective response to, placebo marijuana.

Self-administration of, and subjective response to, placebo marijuana were studied in two groups of regular marijuana smokers. One group received the drug under a set of instructions that informed them that the marijuana was active (deceptive administration); the other group was informed that the marijuana might be inactive (double-blind administration). Subjects were allowed to smoke placebo marijuana freely for 60min during four identical weekly sessions. Subjects smoked an average of 6.0 half-length cigarettes per session, resulting in a mean increase in expired air carbon monoxide of 14.6 ppm. Placebo self-administration did not change significantly across the four sessions. Smoking was associated with marijuana-like subjective effects. Subjects in the deceptive administration group smoked more placebo marijuana and reported a greater subjective response than the other group during the first session only. Several anamnestic factors (drug use history, current pattern of marijuana use, dimensions of personality) correlated with the amount of placebo self-administered, and subjects with less marijuana experience tended to report stronger subjective responses to the placebo. These results demonstrate the importance of including a placebo control when studying the reinforcing effects of marijuana and identify some factors that might predict placebo responses to marijuana or other drugs.

Journal Article↗
PubMed2001

Midazolam sedation in mechanically ventilated newborns: a double blind randomized placebo controlled trial.

OBJECTIVE: To determine efficacy of midazolam as a sedative in mechanically ventilated newborns. DESIGN: Double blind randomized placebo controlled trial. SETTING: Neonatal Unit of Tertiary Hospital. OUTCOME: Sedation over 48 h of observation. METHODS: Neonates with birth weight less than 2000 g who were mechanically ventilated within 7 days of life were randomly assigned to midazolam and placebo group. Midazolam and placebo were administered as bolus (0.2 mg/kg) followed by continuous infusion (0.06 mg/kg/h). Both groups received morphine infusion (10 microg/kg/h). Sedation score was noted at 6 hourly intervals for 48 hours. Hemodynamic variables, ventilatory variables, complications and side effects of treatments were also recorded. RESULTS: Thirty-three neonates were enrolled (17 in midazolam, 16 in placebo group). The groups were comparable for birth weights and gestation. The midazolam group had significantly better sedation from 18-24 hours after enrollment compared to placebo group. At 48 h there were no significant differences in proportion of infants with adequate sedation between midazolam and placebo group. The two groups were comparable with respect to heart rate, perfusion, ventilatory indices and blood gas parameters. None of the infants were noted to have hypotension on loading with midazolam or placebo. Seizures were noted in 2 neonates in placebo group 24 hours after enrollment (insignificant statistically). CONCLUSION: Sedation provided by continuous infusion of midazolam and morphine appears to be comparable to morphine alone in newborn babies on mechanical ventilation, with no significant adverse effects. The course of mechanical ventilation is not influenced by use of midazolam.

Procedural Sedation↗
PubMed1999

A randomized double-blind placebo-controlled study of lamivudine in the treatment of patients with chronic hepatitis B virus infection.

OBJECTIVE: To evaluate the effect of lamivudine on the loss of serum hepatitis B virus (HBV) DNA, HBeAg/antiHBe seroconversion and ALT levels in chronic hepatitis B patients and its safety profile and tolerance compared with placebo. METHODS: Four hundred and twenty-nine patients with chronic HBV infection as defined by positive HBsAg, HBeAg and HBV DNA were enrolled and randomized into lamivudine and placebo groups. Three hundred and twenty-two patients received lamivudine 100 mg daily and 107 patients received placebo treatment for 12 weeks. Then, all patients were offered a further 9-month open label lamivudine treatment. The efficacy and safety were evaluated with clinical, biochemical, hematological and virological parameters. RESULTS: During the 12-week treatment period, 92.2% of lamivudine treated patients became HBV DNA negative (below 1.6 pg/ml) compared with only 14.1% of those receiving placebo (P < 0.01). At the end of 12 week, the sustained negative rate for HBV DNA in the lamivudine treated group was 78.5% compared with the placebo group (11.1%; P < 0.01). There was a trend to a high proportion of patients treated with lamivudine to lose HBeAg (8.1%) and develop antiHBe (10.2%) than treated with placebo (5.3% and 6.4% respectively), but this difference was not statistically significant. Patients with elevated ALT levels at baseline became normal in 60. 3% of the lamivudine treated group compared with the placebo group where only 27.5% were normal (P < 0.01). Lamivudine was well tolerated in a dose of (100 mg daily) and the overall incidence of adverse events was similar to that of the placebo. CONCLUSIONS: Lamivudine (100 mg daily) is very effective in the inhibition of HBV replication, indicated by the rapid loss of serum HBV DNA, and often accompanied by a decrease of serum ALT levels. Lamivudine is well tolerated without severe adverse events during treatment.

Adolescent↗
PubMedDate not supplied

Treatment of venous ulcers with pentoxifylline: a 12-month, double-blind, placebo controlled trial. Microcirculation and healing.

The aim of this study was the evaluation of the treatment of venous ulcers with pentoxifylline (PXF) in 12 months. This double-blind, placebo-controlled trial was conducted in GCP. Patients were included after consent and randomized for PXF (400 mg three times daily) or placebo. The number of healed ulcers, the variation in the area of ulceration, and the variation in microcirculatory parameters (laser-Doppler flux and skin PO2) were considered as endpoints. Of the 85 patients included, 80 completed the study (41 in the PXF and 39 in the placebo group). The groups were comparable. Healing occurred in 88% of limbs in the PXF and in 44% in the placebo group (44% difference; p<0.02). The average area reduction was 93% in the PXF and 56% in the placebo group. Microcirculation was significantly improved in both groups at 12 months. The decrease in flux and the increase in PO2 were greater in the PXF group (p<0.05). Considering the proportion of healed ulcers a better outcome was observed with PXF (p<0.02; 12% of nonhealed ulcers in the PXF vs 56% in the placebo group). The ulcerated area decreased 93% in the PXF vs 56% in the placebo group (40% difference; p<0.02). Tolerability was comparable (6% in the PXF group and 5% in the placebo group complained for treatment). No important side effects were observed. In conclusion, treatment with PXF in venous ulcers improves healing and microcirculation and should be considered in slow-healing venous ulcers.

Aged↗
PubMed2003

Safety and immunoenhancing effect of a Chlorella-derived dietary supplement in healthy adults undergoing influenza vaccination: randomized, double-blind, placebo-controlled trial.

BACKGROUND: Enhancement of immune function has been claimed as a benefit of some natural health products, although few have been subjected to randomized clinical trials. We evaluated the effect of an oral dietary supplement derived from the edible microalga Chlorella pyrenoidosa on immune response after influenza vaccination. METHODS: We conducted a randomized, double-blind, placebo-controlled community-based clinical trial in a convenience sample of 124 healthy adults at least 50 years of age randomly assigned to receive the study product (200 or 400 mg of a Chlorella-derived dietary supplement) or placebo. Participants took the study product or placebo once daily for 28 days. On day 21, we administered a single dose of a licensed trivalent, inactivated influenza vaccine. We obtained serum specimens to measure hemagglutination inhibition titres before and 7 and 21 days after vaccination. The primary immunological outcomes were the proportion of participants with a 4-fold or greater increase in antibodies and geometric mean antibody titres after vaccination; the proportion of participants reporting adverse events during therapy was the safety outcome. RESULTS: A total of 117 (94%) participants completed all aspects of the study. There were no differences in the proportions of recipients of 200 or 400 mg of the Chlorella-derived dietary supplement or placebo who achieved at least a 4-fold increase in antibodies (proportions for the 3 virus strains ranged from 17.9% to 28.2% for the 200-mg group, from 11.1% to 22.2% for the 400-mg group and from 19.0% to 21.4% for the placebo group; p > 0.05 for all comparisons). Reports of adverse events were similar for recipients of the supplement and placebo, except with regard to fatigue, which was reported more frequently by recipients of 200 mg of the supplement (18/41 or 44%) than by those who received 400 mg of the supplement (8/40 or 20%; p = 0.032) or placebo (8/42 or 19%; p = 0.019). Recipients of 400 mg of the supplement who were 55 years of age or younger had significantly higher geometric mean antibody titres against influenza A/New Caledonia 21 days after vaccination (p = 0.047) and against B/Yamanashi 7 days after vaccination (p = 0.034); the trends were nonsignificant for titres against A/Panama. We also observed similar increases for the proportions of subjects with a 2-fold or greater or a 4-fold or greater increase in antibodies. INTERPRETATION: The Chlorella-derived dietary supplement did not have any effect in increasing the antibody response to influenza vaccine in the overall study population, although there was an increase in antibody response among participants aged 50-55 years. Adverse events were similar among those receiving the supplement and the placebo. Further studies are warranted to explore the range of clinical effects resulting from ingestion of this dietary supplement.

Adjuvants, Immunologic↗
PubMed2002

Efficacy of a novel chitosan formulation on fecal fat excretion: a double-blind, crossover, placebo-controlled study.

The ability of a novel chitosan formulation to influence gastrointestinal fat absorption in vivo was examined in a double-blind, placebo-controlled, crossover study by determining the content of total fat in feces in two groups of subjects. Twenty-nine normal healthy subjects were recruited for the study. Twenty-four participants completed the test period with the chitosan formulation, and 21 completed the placebo phase of study. During the placebo and the test periods, the subjects were administered six capsules three times daily 10 minutes before meals for three days and for the two days of the stool collection. A daily serving of six tablets of the test compound contained 2100 mg chitosan and 300 mg psyllium husk seeds. In respect to the baseline period, the test compound increased fat excretion significantly whether the test period preceded or proceeded the placebo period (p<0.02 and p<0.05 respectively). In contrast, essentially no changes were seen during the placebo loading periods. Compared to the difference between placebo period and its baseline period, a statistically significant increase in fecal fat excretion was observed over baseline following oral supplementation of a novel formulation of chitosan and psyllium husk seeds [+3.63 gm/day +/- 0.83 (SEM) vs. -0.15 gm/day +/- 0.94 (SEM) (p=0.004)]. The average daily increase in fecal fat of 3-4 grams over control could account for a decrease in calorie consumption of 30-40 kcal per day. A total of 19 subjects completed both parts of the study. Examining the data from these 19 subjects by ANOVA, it was found that the period when the test compounds were given was statistically significantly different from the placebo baseline, placebo experimental, and test baseline periods. Using multiple comparisons, it was ascertained that the novel formulation containing chitosan plus psyllium husk seeds increases fecal fat excretion.

Adult↗
PubMed1992

[Intravenous thrombolysis by recombinant plasminogen activator (rt-PA) in unstable angina. A randomized multicenter study versus placebo].

Fifty patients (38 men) with unstable angina pectoris defined by: pain lasting > 15 minutes+percritical electrocardiographic changes+significant coronary narrowing on coronary angiography (Coro 1) performed within 24 hours, were treated in a double blind protocol with rt-PA (n = 25) 100 mg/90 minutes (10 mg bolus + 90 mg/90 minutes or placebo (n = 25). All received effective intravenous heparin and intravenous nitrates. Calcium antagonists and betablockers were prescribed in half the cases. Aspirin (100 mg orally per day) was prescribed after control coronary angiography (Coro 2) performed 24 +/- 6 hours after starting treatment. Qualitative and quantitative analysis (CAESAR system) was centralised. There were no differences in the angiographic findings between the two groups. Intracoronary thrombosis was observed in 43% (rt-PA) and 44% (placebo) in Coro 1 and in 17% and 28% in Coro 2. The incidence of myocardial revascularisation procedures was similar in the two groups: angioplasty: 12 (rt-PA) and 13 (placebo); coronary bypass surgery: 5 (rt-PA) and 6 (placebo). Seven patients developed myocardial infarction (5 rt-PA, 2 placebo), one of whom died of cardiogenic shock (placebo). Eighteen patients had haemorrhagic complications (14 rt-PA, 4 placebo; p < 0.002) mainly at the puncture sites (12/14, 3/4). Spontaneous haemorrhage occurred in 7/25 (28%) of patients on rt-PA (haematuria 3, gastrointestinal haemorrhage 2, haematuria + gastrointestinal haemorrhage 1, epistaxis 1) and in 1/25 patients on placebo (gastrointestinal haemorrhage) This study shows that intravenous thrombolysis with rt-PA in severe unstable angina pectoris doe not modify the clinical outcome or the angiographic lesions but exposes patients to a high risk of haemorrhagic complications.

Adult↗
PubMedDate not supplied

Efficacy of extract of Pelargonium sidoides in children with acute non-group A beta-hemolytic streptococcus tonsillopharyngitis: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Clinical trial data suggest that antibiotics are not indicated for the treatment of acute non-group A beta hemolytic strep (non-GABHS) tonsillopharyngitis. Nevertheless patients are symptomatic and effective alternatives for its treatment are needed that have been evaluated in clinical trials. OBJECTIVE: To confirm that treatment with an extract of Pelargonium sidoides (EPs 7630) is superior to placebo for the treatment of non-GABHS tonsillopharyngitis in children. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Six study sites in 4 pediatric and ENT primary care outpatient clinics. PATIENTS: One hundred forty-three children aged 6-10 years with non-GABHS tonsillopharyngitis present < or = 48 h, a negative rapid strep screen, a Tonsillopharyngitis Severity Score (TSS) > or = 8 points, and informed consent. INTERVENTION: EPs 7630 or placebo (20 drops tid) for 6 days. MEASUREMENT: The primary outcome criterion was the decrease of the TSS from baseline (day 0) to day 4. RESULTS: The decrease of the TSS from baseline (day 0) to day 4 was 7.1 +/- 2.1 points under EPs 7630 (n = 73), and 2.5 +/- 3.6 points under placebo (n = 70). The covariate adjusted decrease was 7.0 +/- 2.4 points under EPs 7630, and 2.9 +/- 2.4 points under placebo. The 95% RCI for the difference between the groups was [2.7; 4.9] demonstrating a significant difference in efficacy of EPs 7630 compared to placebo (P < 0.0001). Adverse events (AEs) occurred in 15/143 patients (EPs 7630: 4/73 patient, placebo: 44/70) and were not related to the investigational medication. CONCLUSIONS: EPs 7630 was superior compared to placebo for the treatment of acute non-GABHS tonsillopharyngitis in children. Treatment with EPs 7630 reduced the severity of symptoms and shortened the duration of illness by at least 2 days.

Acute Disease↗
PubMedDate not supplied

Efficacy and safety of oral tibolone 1.25 or 2.5 mg/day vs. placebo in postmenopausal women.

BACKGROUND: tibolone at usual doses of 2.5 mg/day in postmenopausal women has been shown to improve climacteric complaints, without affecting endometrial thickness and lipid profile or blood glucose. However, the potentially similar efficacy, but better tolerability, of a low dose of this drug (1.25 mg) has never been established. METHODS: 162 healthy, non-obese, post-menopausal women, aged 40-65 years, with an intact uterus were enrolled in a national, single centre, randomised, double blind, placebo controlled, parallel group trial. After 1 week of runin, patients were treated for 24 weeks with placebo, tibolone 1.25 mg or 2.5 mg/day. During the study laboratory tests, endometrial ultrasound scans and mammography were performed. Occurrence of menopausal signs and symptoms, including vaginal bleeding, and quality of sexual life were also checked. RESULTS: in the 120 patients terminating the study without major protocol violations, climacteric symptoms were similarly improved by tibolone 1.25 and 2.5 mg (78% and 90% reduction at week 24 for hot flushes, 36% and 34% for sweating episodes and 44% and 51% for vaginal dryness), but not by placebo. Benefits occurred earlier in the group treated with tibolone 2.5 mg. Quality of sexual life was almost invariably improved by tibolone as compared to placebo, but improvement occurred earlier in the tibolone 1.25 mg group. Severity of vaginal bleeding was not different between placebo and active treatment groups, except at week 12 when was higher. At the end of treatment vaginal bleeding occurred in 15% of patients treated with placebo, 14% treated with tibolone 1.25 mg and 12% treated with tibolone 2.5 mg. Endometrial thickness and breast density were not changed by treatment, as well as FSH, 17-beta-estradiol, total cholesterol, HDL and LDL cholesterol, triglycerides and blood glucose. Adverse events were reported by 14.7%, 26.7% and 24.4% of patients treated with placebo, tibolone 1.25 mg and tibolone 2.5 mg/day, respectively. CONCLUSIONS: tibolone at doses of 1.25 or 2.5 mg/day given for 24 weeks to postmenopausal women displayed similar efficacy and safety profiles, though were more effective than placebo. Tibolone 1.25 mg induced a more gradual relief from climacteric symptoms and a more prompt improvement of sexual function.

Administration, Oral↗
PubMed2004

Effects of raloxifene hydrochloride on bone mineral density, bone metabolism and serum lipids in Chinese postmenopausal women with osteoporosis: a multi-center, randomized, placebo-controlled clinical trial.

BACKGROUND: Raloxifene has been approved for prevention and treatment of postmenopausal osteoporosis in Caucasian women. It also has some positive effects on serum lipids in Caucasians. The objective of this study was to determine the effect of raloxifene hydrochloride on lumbar spine and total hip bone mineral density (BMD), bone metabolism, and serum lipids in Chinese postmenopausal women with osteoporosis. METHODS: This was a multi-center, randomized, double-blind, placebo-controlled clinical trial in which 204 postmenopausal Chinese women with osteoporosis were assigned to receive raloxifene (60 mg) or placebo treatment daily for 12 months. BMD, serum bone metabolism markers, and serum lipids were measured before and after drug administration. BMD was measured by Dual-Energy X-Ray Absorptiometry (DEXA) and bone metabolism markers were analyzed by one-step enzyme-linked immunosorbent assay. Serum lipids were measured by enzymatic analysis. RESULTS: At the end of the 12-month study, lumbar spine BMD increased in both groups with a mean increase of (3.3 +/- 4.8)% in the raloxifene group and (1.0 +/- 4.9)% in the placebo group (P < 0.001). There was a mean increase in total hip BMD of (1.4 +/- 4.8)% in the raloxifene group and a mean decrease of (0.9 +/- 5.0)% in the placebo group (P < 0.001). No subject in the raloxifene group had a new vertebral fracture and 5 placebo subjects had new fractures (P > 0.05). In the raloxifene group, the median decreases in the biochemical markers of bone metabolism serum osteocalcin and C-telopeptide were 41.7% and 61.5%, respectively. These changes were statistically significant compared with those in the placebo group (10.6% and 35.6%, P < 0.001, respectively). Both total cholesterol and low-density lipoprotein cholesterol decreased significantly in the raloxifene group compared with those in the placebo group (P < 0.001, respectively) and there was no significant effect of raloxifene on high-density lipoprotein cholesterol and triglycerides compared with placebo. CONCLUSIONS: Raloxifene 60 mg/d for 12 months significantly increases lumbar spine and total hip BMD, significantly decreases bone turnover, and has favourable effects on serum lipids in Chinese postmenopausal women with osteoporosis.

Aged↗
PubMed2005

Reassessment of defibrase in treatment of acute cerebral infarction: a multicenter, randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of defibrase in patients with acute cerebral infarction by a large sample, multicenter, randomized, double-blind, placebo-controlled clinical trial. METHODS: Patients with acute cerebral infarction within 12 hours of stroke onset were randomly assigned to receive either an initial intravenous infusion of defibrase 15 U plus normal saline 250 mL or 250 mL of normal saline only. Subsequent infusions of defibrase 5 U or placebo (normal saline) were given on the 3rd, 5th, 7th, and 9th day, respectively. Both groups received standard care of acute cerebral infarction. The primary efficacy outcome was functional status (Barthel Index) at 3 months after treatment. Safety outcome were bleeding events and mortality rate. Secondary outcome included Chinese Stroke Scale (CSS) score at 14 days and recurrence rate of stroke at 1 year. RESULTS: A total of 1053 patients were enrolled at 46 centers from September 2001 to July 2003, and 527 patients were randomly assigned to receive defibrase and 526 to receive placebo. A similar proportion of patients in both groups completed a full course of treatment. There was a significantly greater proportion of favorable functional status (Barthel Index > or = 95) in defibrase group than in placebo group at 3 months (52.2% vs. 42.8%, P < 0.01), and the proportion of dependent functional status (Barthel Index < or = 60) was a little lower in defibrase group compared with placebo group (27.7% vs. 32.4%). These differences were more obvious among patients who were treated within 6 hours of stroke onset. Patients in defibrase group had better improvement with respect to CSS score than those in placebo group at 14 days (P < 0.05). Recurrence rate of stroke at 1 year was lower in the defibrase group compared with placebo group (6.2% vs. 10.1%, P = 0.053). Patients in defibrase group had higher risk of extracranial bleeding events (4.7% vs. 1.5%, P < 0.01) and a tendency of higher risk of symptomatic intracranial hemorrhage. The hemorrhage incidence was higher in patients with fibrinogen level < 130 mg/dL than > or = 130 mg/dL (10.6% vs. 3.8%, P < 0.05). Mortality rate at 3 months were slightly higher in defibrase group than placebo group (5.9% vs. 4.2%). CONCLUSIONS: The defibrase is effective to improve neurological function and function of daily living for patients with acute cerebral infarction within 12 hours of symptom onset. The efficacy was even better for acute cerebral infarction within 6 hours of onset. The increased risks of intra- and extracranial hemorrhage during defibrase administration were related to the plasma fibrinogen level.

Adult↗
PubMed2005

Effectiveness of the addition of ezetimibe to ongoing statin therapy in modifying lipid profiles and attaining low-density lipoprotein cholesterol goals in older and elderly patients: subanalyses of data from a randomized, double-blind, placebo-controlled trial.

BACKGROUND: The Ezetimibe Add-on to Statin for Effectiveness (EASE) trial examined the effectiveness and safety profile of ezetimibe (EZE) added to ongoing statin therapy in 3030 patients with low-density lipoprotein cholesterol (LDL-C) levels exceeding National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP 111) goals. OBJECTIVE: Because people aged > 65 years are at increased risk for development of coronary heart disease (CHD), these subgroup analyses of data from the EASE trial were conducted to determine the extent of change in LDL-C levels and attainment of NCEP ATP III LDL-C goals with the addition of EZE to ongoing statin therapy in patients aged 65 to 74 years (the older group) and > or = 75 years (the elderly group). METHODS: In the multicenter (299 sites), community-based, double-blind, placebo-controlled EASE trial, patients were randomly assigned in a 2:1 ratio to receive EZE 10 mg/d or placebo in addition to their ongoing statin therapy for 6 weeks. The primary efficacy end point was the percent reduction in LDL-C levels, and the principal secondary end point was the proportion of patients achieving NCEP ATP III target LDL-C levels. The effects of the addition of EZE on additional lipid and lipoprotein measures and high-sensitivity C-reactive protein were also examined, as was tolerability. Study analyses were performed in the modified intent-to-treat population. RESULTS: This subgroup analysis included data from 841 patients in the older age group (579 EZE + statin, 262 placebo + statin), which constituted 27.8% of the overall EASE population, and 466 in the elderly group (307 EZE + statin, 159 placebo + statin), which constituted 15.4% of the overall EASE population. The former group included 436 (51.8%) men and 405 (48.2%) women, with a mean (SD) age of 69.2 (3.0) years; the latter group included 227 (48.7%) men and 239 (51.3%) women, with a mean age of 78.5 (3.2) years. The characteristics of the 2 groups were comparable at baseline. In the older group, 717 (85.3%) had CHD or a CHD risk equivalent, as did 421 (90.3%) of those in the elderly group. Thirty-two patients in the older group and 17 in the elderly group discontinued the study. The reasons for discontinuation included clinical adverse events (n = 23), withdrawal of consent (n = 15), loss to follow-up (n = 4), protocol deviation (n = 2), and other reasons (n = 5). EZE + statin significantly reduced LDL-C compared with placebo + statin (older group: mean [SE] treatment difference, -25.1% [1.4]; P < 0.001; elderly group: treatment difference, -22.0% [1.8]; P < 0.001). The LDL-Glowering effects of treatment were consistent in the 2 groups. EZE + statin therapy significantly improved other lipid parameters (triglycerides, non high density lipoprotein cholesterol, and total cholesterol, P < 0.001 in both age groups; high-density lipoprotein cholesterol, P < 0.03 in the older group only) and high-sensitivity C-reactive protein levels compared with EZE + placebo (P < 0.03). The attainment of LDL-C goals also was significantly increased with EZE + statin compared with placebo + statin (older group: 72.3% vs 18.9%, respectively; odds ratio [OR] = 14.59; 95% CI, 9.55 to 22.28; P < 0.001; elderly group: 73.3% vs 18.9%; OR = 13.44; 95% CI, 7.72 to 23.41; P < 0.001). EZE + statin therapy was well tolerated by patients in both age groups, with a safety profile comparable to that of placebo + statin. CONCLUSIONS: In these older and elderly patients, many of them at high risk for CHD, EZE added to ongoing statin therapy was well tolerated and was an effective treatment option for improving lipid profiles and attainment of LDL-C goals. Adding EZE improved rates of attainment of NCEP ATP III LDL-C goals without increases in the dose or potency of statin therapy. Further studies are necessary to determine whether these results can be generalized to other older and elderly populations.

Aged↗
PubMed1989

Chronic effects of transdermal nitroglycerin in stable angina pectoris: a within-patient, placebo-controlled study.

The efficacy of transdermal nitroglycerin patches, releasing 20 mg of active substance over a period of 24 h (TDN 20), was investigated in 10 patients with stable exercise-induced angina pectoris. The study was divided into 3 periods: the first part was an acute, within-patient, crossover, double-blind, placebo-controlled study, in which patients performed a cycloergometric exercise test 4 and 24 h after the application of the patches (TDN 20 or placebo). During the 2nd period, patients were given TDN 20, in single blind conditions, for 4 weeks and another exercise test was performed, on the last day, 4 and 24 h after patch application. Finally, after a one-day placebo wash-out, a second acute study similar to the first was performed. Four h after dosing, exercise duration to 1 mm ST segment depression was 441 s and 314 s (p less than 0.01) for TDN 20 and placebo, respectively (first acute study), 394 s for TDN 20 after chronic treatment (p less than 0.001 vs acute placebo) and 472 and 354 s (p less than 0.001) for TDN 20 and placebo, respectively (second acute study). No difference in exercise duration to 1 mm ST segment depression was found between TDN 20 and placebo, 24 h after administration, in any of the periods. Blood pressure significantly decreased and heart rate significantly increased 4 h after TDN dosing (in comparison with placebo) in both the acute studies, but no difference was observed after chronic TDN treatment. In conclusion, TDN 20 increases exercise tolerance 4 h after the application of both acute and chronic treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1986

Effects of a transdermal patch system containing nitroglycerin on exercise tolerance in patients with angina pectoris. Double-blind, placebo controlled, comparison with slow-release nifedipine and verapamil.

The antianginal efficacy of nitroglycerin (NTG), given in a new transdermal therapeutic system (TTS), was compared with that of nifedipine and verapamil, both in slow-release (SR) formulation, in a randomized, double-blind, placebo-controlled study, carried out in 8 patients with stable exercise-induced angina pectoris. TTS NTG 40 cm2 (releasing 20 mg of NTG over 24 hours), nifedipine 20 mg SR, verapamil 120 mg SR and placebo were given once on 4 consecutive days according to a 4 X 4 latin-square design, twice replicated. A cycloergometric symptom-limited exercise test was performed 4 and 8 hours after the administration of each drug. Four hours post-dosing, mean exercise duration was 407 sec. after placebo and 523 (+28%) and 485 (+ 19%) sec. after TTS NTG and nifedipine SR respectively, while at the 8th hour it was 375 sec. after placebo, and 515 (+ 37%) and 457 (+ 21%) sec. after TTS NTG and nifedipine SR. Exercise duration after verapamil was similar to that after placebo. In comparison with placebo maximal workload and total work performed were significantly higher on TTS NTG and on nifedipine at both times of observation, but no significant differences were seen after verapamil. Peak exercise systolic blood pressure was nearly identical after all the treatments tested. Peak exercise heart rate and pressure rate product were both significantly higher on TTS NTG, as well as on nifedipine, in comparison with placebo, while values after verapamil did not differ from those after placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1995

[Value of the combination of trimetazidine (Vastarel 20 mg) with diltiazem (Tildiem 60 mg) in stable effort angina. A double-blind versus placebo multicenter study].

Trimetazidine is a cytoprotective anti-ischaemic agent whose antianginal efficacy has been demonstrated in monotherapy versus placebo and versus reference products, and in combination with beta-blockers and nifedipine. As coprescription with diltiazem has not been previously studied, the objective of this study was to evaluate the benefit of the addition of trimetazidine (60 mg/24 h) to diltiazem (180 mg/24 h) in the stable exertional angina insufficiently improved by calcium channel blocker alone. This multicentre double-blind placebo-controlled study was conducted over a period of 6 months. The inclusion criteria were stable angina with electrically positive stress test, which remained positive despite a 15-day treatment with diltiazem (180 mg/24 h). It was conducted in 67 patients randomized into two groups: diltiazem-placebo (group I: 35 patients) and diltiazem-trimetazidine (group II: 32 patients). The follow-up consisted of clinical assessment and a stress test on inclusion and at 6 months. The two groups were similar on inclusion for all ergometric parameters, excepted for the time to onset of the ischaemic threshold of 1 mm and the total duration of effort, which were significantly longer in the placebo group. Comparison of the stress tests performed at the sixth month and on inclusion between groups I and II showed that the ischaemic threshold of 1 mm was significantly delayed by 2 minutes 41 seconds in the trimetazidine group (p < 0.001) versus 42 seconds in the placebo group (NS). Similarly, the work performed at this threshold was significantly increased by 1446 kpm in the trimetazidine group (p < 0.001) versus 564 kpm in the placebo group (p = 0.012). The difference between the two groups was significant for these two parameters, p = 0.008 and p = 0.018, respectively. At maximum effort, the total duration and the total work also increased significantly in the trimetazidine group, by 50 seconds (p = 0.006) and 570 kpm (p = 0.004), respectively, versus 16 seconds and 221 kpm in the placebo group (NS). The [double product (SBP x HR)/load (in watts)] ratio at the ischaemic threshold of 1 mm reached at M0, decreased significantly in the trimetazidine group by 69.9 (p < 0.001) versus 20.3 in the placebo group (NS). The difference between the two groups was significant (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1996

Tamsulosin, the first prostate-selective alpha 1A-adrenoceptor antagonist. A meta-analysis of two randomized, placebo-controlled, multicentre studies in patients with benign prostatic obstruction (symptomatic BPH). European Tamsulosin Study Group.

OBJECTIVE: This meta-analysis of two European studies evaluated the efficacy and safety of modified-release tamsulosin 0.4 mg once daily compared with placebo in patients with benign prostatic enlargement, lower urinary tract symptoms and prostatic obstruction (symptomatic BPH). METHODS: Patients entered a 2-week placebo run-in period, followed by randomization to treatment with tamsulosin (382 patients) or placebo (193 patients) once daily for 12 weeks. RESULTS: Maximum urinary flow rate improved to a greater extent in the tamsulosin group (1.6 ml/s, 16%) than the placebo group (0.6 ml/s, 6%) (p = 0.002). Total Boyarsky symptom score also improved to a greater extent in the tamsulosin group (3.3 points, 35.1% reduction) than the placebo group (2.4 points, 25.5% reduction) (p = 0.002). Significantly more tamsulosin patients (66%) than placebo patients (49%) had a > or = 25% decrease in total symptom score at endpoint (p < 0.001). Twelve weeks of treatment with tamsulosin also produced significant improvements in average urinary flow rate (p = 0.005) and voiding or "obstructive" (p = 0.008) and storage or "irritative' (p = 0.017) symptom scores. The incidence of drug-related adverse events was comparable for the tamsulosin and placebo groups (13 and 12% respectively, p = 0.802). The same applies to the incidence of adverse events commonly attributed to alpha 1-adrenoceptor antagonists, such as dizziness, headache, postural hypotension, syncope, asthenia, somnolence and rhinitis. There were no clinically significant changes in blood pressure or pulse rate in tamsulosin patients compared with placebo patients both in hypertensive and normotensive BPH patients. CONCLUSION: Tamsulosin 0.4 mg once daily is safe, well-tolerated and improves both the symptoms and urinary flow rate in patients with benign prostatic obstruction (symptomatic BPH).

Administration, Oral↗