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PubMed1988

The methodological and clinical aspects of the placebo effect in angina pectoris.

The study was carried out in 45 patients (36 males and 9 females) experiencing more attacks on the evaluation of an antianginal drug in a placebo-controlled trial, and to define some conditions of placebo sensitiveness in patients with angina pectoris. The study was carried out in 45 patients (36 males and 9 females) experiencing more than 5 anginal attacks a week. The drug compared with the placebo was Iso-Mack-Retard 20 believed to have a good antianginal profile. The efficacy of both the drug and placebo was assessed mainly by the number of anginal attacks per week. The differences in the efficacy between the drug and its placebo in the group studied as a whole were not statistically significant but, after exclusion of 15 placebo-sensitive patients (placebo responders), these differences increased to become statistically significant (p less than 0.01). Moreover, the study proved that the extent of the placebo effect in a population is inversely dependent on the level of neuroticism measured by Eysenck Personality Inventory, and directly dependent on the number of anginal attacks in the period before administration of the drug.

Adult↗
PubMed1987

[The placebo as a nonspecific treatment factor].

Nonspecific drug actions result from the social interaction between physician and patient and the medical environment. Positive (therapeutic) placebo effects are produced in approximately 30-35% of treated patients, especially in cases of vegetative and psychic disturbances. There appears to be no distinct group of individuals with specific personality features that can be classified as "placebo responders". Negative (toxic) placebo effects, which are usually minor, are reported in 4-50% of treated patients. The occurrence of side effects may cause the patient to assume treatment with an active agent, thus increasing the therapeutic efficiency of the treatment (placebo amplification by side effects). On the other hand, the lack of a certain side effect may diminish the therapeutic effect of an active drug. The notion that placebo-induced analgesia is endorphin-mediated is not established. Hence at present psychological mechanisms have to be assumed for the placebo effect. The conscious use of a placebo as a therapeutic agent is problematic for ethical reasons, whereas the placebo component of drugs with specific actions should be exploited to enhance their therapeutic efficiency.

Humans↗
PubMed1995

A double-blind comparison of Org 3770, amitriptyline, and placebo in major depression.

BACKGROUND: A 6-week, double-blind, dose titration study was performed to evaluate efficacy and safety of the new antidepressant Org 3770 in comparison with amitriptyline and placebo. METHOD: One hundred fifty outpatients of both sexes, 18 years and older, with a DSM-III diagnosis of major depressive episode, were randomly assigned to 6 weeks of treatment with Org 3770, amitriptyline, or placebo. RESULTS: At baseline, mean 17-item Hamilton Rating Scale for Depression (HAM-D) scores of all treatment groups were higher than 25, thus indicating that a large proportion of severely depressed patients entered the study. The overall mean daily doses were 22 mg/day for Org 3770, 133 mg/day for amitriptyline, and 4.9 capsules/day for placebo. The majority of times assessments were made, both active drugs produced significantly greater improvements than placebo on all efficacy variables (17-item HAM-D, Montgomery-Asberg Depression Rating Scale, Clinical Global Impressions, and Zung Self-Rating Depression Scale). After 6 weeks of treatment, significantly greater (p < or = .05) proportions of patients in both active treatment groups (70% in the Org 3770- and 58% in the amitriptyline-treatment groups) than in the placebo-treatment group (33%) were HAM-D responders. Org 3770 was well tolerated in this study; dry mouth and somnolence were the only adverse experiences that occurred significantly more frequently with Org 3770- than with placebo-treated patients. By contrast, treatment with amitriptyline was related to significantly higher rates of dry mouth, constipation, and dyspepsia as compared with both Org 3770 and placebo, and significantly higher rates of somnolence as compared with placebo. CONCLUSION: In this study, Org 3770 was as effective as amitriptyline in the treatment of major depression, with advantages regarding improvements of depressed mood (HAM-D Item 1), responder rates, and safety.

Amitriptyline↗
PubMed1995

A comparison of placebo responders and nonresponders in subgroups of depressive disorder.

The objective of this study was to determine if the placebo treatment response varied in subgroups of depressed patients (single episode, recurrent, and double depression). Data from placebo-treated patients from seven placebo-controlled clinical trials were pooled and analyzed retrospectively. The placebo response rate was highest for females with a single episode of depression (66.7%) and lowest for females with recurrent depressive episodes (13.3%). Among patients experiencing their first episode, placebo responders had lower Hamilton Rating Scale for Depression (HAMD) total scores at baseline and lower ratings of pschomotor retardation than nonresponders. For patients having a recurrence of an episode, placebo responders had lower baseline ratings of somatic anxiety. The major finding was that patients suffering from their first depressive episode differed from patients with recurrent depressive episodes in the rate of placebo response, effect of gender, and the clinical symptoms that were associated with a positive placebo response.

Antidepressive Agents↗
PubMed1995

Steroid sparing activity of tenidap in patients with polymyalgia rheumatica: a multicenter double blind randomized placebo controlled study.

OBJECTIVE: To determine whether tenidap treatment would allow reduction or replacement of systemic corticosteroid treatment in patients with polymyalgia rheumatica (PMR). METHODS: A 15-week double blind, randomized, multicenter, placebo-controlled study of tenidap sodium (120 mg/day) in patients with symptomatically controlled PMR receiving 10 mg/day prednisone was conducted. After receiving study drug for 3 weeks, prednisone dose was reduced by 2.5 mg/day every 3 weeks. The lowest clinically effective dose of prednisone was recorded as 10, 7.5, 5, 2.5 or 0 mg/day. RESULTS: Thirty-two patients were randomized to tenidap or placebo. As prednisone was reduced more placebo patients experienced an exacerbation of PMR symptoms, elevation of erythrocyte sedimentation rate and increased serum C-reactive protein. Twice as many placebo patients (10 of 16) as tenidap patients (5 of 16) discontinued due to lack of efficacy. The lowest effective dose of prednisone could be determined in 27 of the 32 patients, 11 receiving tenidap and 16 placebo. A significantly (p = 0.027) greater proportion of patients receiving tenidap (5 of 11) than placebo (1 of 16) were able to discontinue prednisone without experiencing a symptomatic flare. CONCLUSION: As prednisone was reduced, symptoms of PMR were controlled better by tenidap than by placebo. Forty-five percent of evaluable patients receiving tenidap were able to discontinue prednisone without a disease flare compared to 6% for placebo.

Aged↗
PubMed1995

[Efficacy and tolerance of an effervescent aspirin-metoclopramide combination in the treatment of a migraine attack. Randomized double-blind study using a placebo].

OBJECTIVES: A double blind, randomized, multicenter, parallel group study was carried out to compare the efficacy and tolerance of aspirin 900 mg-metoclopramide 10 mg effervescent association (AAM) with those of placebo in the treatment of acute migraine attack. All patients were selected according to the International Headache Society criteria. METHODS: A total of 303 out-patients with an acute migraine attack were treated orally with either AAM (n = 152) or placebo (n = 151). RESULTS: The aspirin-metoclopramide association was significantly more effective than placebo at relieving headache (principal criterion) within 2 h of treatment (54.3% versus 25.9% : p < 0.001), producing entire resolution of acute migraine attack (14.2% versus 5.3% : p = 0.017), reducing the percentage of patients requiring rescue medication (44.3% versus 63.2% : p = 0.001) and increasing the percentage of patients able to resume their usual activities (44.1% versus 22.1% : p = 0.003). AAM also provided more frequent relief from associated symptoms as compared with placebo (37.4% versus 22.1% : p = 0.006). The therapeutic efficacy was rated as good or excellent by 39.7% of patients in the AAM group compared with 20.7% in the placebo group (p < 0.001). Moreover 64.2% of AAM treated patients said they would be prepared to take the treatment again compared with 46.4% who received placebo (p < 0.001). The percentage of patients reporting adverse events was not different between the two treatments (20.4% AAM versus 18.5% placebo : p = 0.684). The most commonly reported symptoms were gastro-intestinal disorders. Similar number of gastralgia occurred with AAM (n = 4) and placebo (n = 3). CONCLUSION: It is concluded that the aspirin-metoclopramide association may be used as a first intention treatment of acute migraine attack in out-patients.

Administration, Oral↗
PubMed1993

[Is placebo necessary in a clinical trial on ambulatory blood pressure?].

Placebo has only a slight effect on ambulatory blood pressure (ABP). Some authors have suggested that the use of a placebo is not necessary in a study on the drugs effect on ABP. We demonstrate that even if placebo effect is small, the use of a placebo group is still necessary. Effects of one daily dose of 50 mg atenolol + 20 mg slow-released nifedipine (AN) were investigated. Patients with office DBP 90-110 mmHg received, in a double-blind protocol, either AN (group AN, n = 31) or a placebo (group P, n = 26). Ambulatory BP (ABP) and HR were measured (Spacelabs or Diasys systems) for 24 h before and one month after treatment. The 2 groups were comparable before treatment. After 1 month under treatment, ABP was significantly lower in the AN group, compared to the P group, and this over the whole day (p = 0.03 to p < 0.0001). The effect was the most important between 10-17 h (p < 0.0001). HR was significantly lower in the AN group during daytime (6-22 h), but not during the night (22-6 h). Over the whole group, placebo effect was not significant. However, ABP did decrease under placebo in subjects with high initial pressure. As a result, an analysis without data from the placebo group led to an overestimation of the effects of the drug.

Adult↗
PubMed1997

Abecarnil for the treatment of generalized anxiety disorder: a placebo-controlled comparison of two dosage ranges of abecarnil and buspirone.

BACKGROUND: The development of effective and well-tolerated anxiolytic agents is an area of critical clinical importance. Abecarnil, a beta carboline, is a partial benzodiazepine-receptor agonist that has demonstrated promise as an anxiolytic agent. In this study, we examine the efficacy, safety, and discontinuation-related effects of abecarnil, buspirone, and placebo in the acute and long-term treatment of patients who have generalized anxiety disorder. METHOD: This is a double-blind, placebo-controlled study of two dosages of abecarnil and buspirone. In total, 464 patients were randomized. After a placebo run-in week, patients entered a 6-week double-blind treatment period, followed by an optional 18-week maintenance period for treatment responders. After abrupt discontinuation of the acute or maintenance treatment, patients entered a 3-week placebo-substitution follow-up period. Treatment response was assessed with the Hamilton Rating Scale for Anxiety and the Clinical Global Impressions (CGI) Scale. RESULTS: Compared with placebo, abecarnil showed significant anxiolytic activity early in the treatment period, particularly in the high-dosage group, though these differences did not maintain statistical significance at the end of the trial. Buspirone was associated with a slower onset of action and better symptom relief than placebo after 6 weeks of therapy. Withdrawal symptoms emerged in patients who abruptly discontinued abecarnil (particularly at the higher dosage) only in those receiving a longer duration of treatment. CONCLUSION: The results of this study need to be understood in the context of a high placebo-response rate, which hampers the ability to demonstrate significant drug-placebo differences. This study suggests that abecarnil may be an effective anxiolytic agent; further attention is warranted to assess its spectrum of clinical effectiveness.

Adolescent↗
PubMedDate not supplied

Echinacea root extracts for the prevention of upper respiratory tract infections: a double-blind, placebo-controlled randomized trial.

OBJECTIVE: To investigate the safety and efficacy of 2 extracts of echinacea for preventing upper respiratory tract infections. DESIGN: Three-armed, randomized, double-blind, placebo-controlled trial. SETTING: Four military institutions and 1 industrial plant. PARTICIPANTS: Three hundred two volunteers without acute illness at time of enrollment. INTERVENTIONS: Ethanolic extract from Echinacea purpurea roots, Echinacea angustifolia roots, or placebo, given orally for 12 weeks. MAIN OUTCOME MEASURE: Time until the first upper respiratory tract infection (time to event). Secondary outcome measures were the number of participants with at least 1 infection, global assessment, and adverse effects. RESULTS: The time until occurrence of the first upper respiratory tract infection was 66 days (95% confidence interval [CI], 61-72 days) in the E angustifolia group, 69 days (95% CI, 64-74 days) in the E purpurea group, and 65 days (95% CI, 59-70 days) in the placebo group (P = .49). In the placebo group, 36.7% had an infection. In the treatment groups, 32.0% in the E angustifolia group (relative risk compared with placebo, 0.87; 95% CI, 0.59-1.30) and 29.3% in the E purpurea group (relative risk compared with placebo, 0.80; 95% CI, 0.53-1.31) had an infection. Participants in the treatment groups believed that they had more benefit from the medication than those in the placebo group (P = .04). Adverse effects were reported by 18 subjects in the E angustifolia group, 10 in the E purpurea group, and 11 in the placebo group. CONCLUSION: In this study a prophylactic effect of the investigated echinacea extracts could not be shown. However, based on the results of this and 2 other studies, one could speculate that there might be an effect of echinacea products in the order of magnitude of 10% to 20% relative risk reduction. Future studies with much larger sample sizes would be needed to prove this effect.

Adult↗
PubMed1999

Treatment of active rheumatoid arthritis with leflunomide compared with placebo and methotrexate. Leflunomide Rheumatoid Arthritis Investigators Group.

CONTEXT: Leflunomide is a reversible inhibitor of de novo pyrimidine synthesis shown to be effective in a phase 2 trial in 402 patients with active rheumatoid arthritis (RA). OBJECTIVE: To compare the efficacy and safety of leflunomide treatment with placebo and methotrexate treatment in patients with active RA. DESIGN: Randomized, double-blind, placebo, and active-controlled 12-month study. SETTING: Forty-seven university and private rheumatology practices in the United States and Canada. PATIENTS: Diagnosis of RA by the American College of Rheumatology (ACR) criteria for duration of 6 months or longer and no previous methotrexate treatment. INTERVENTION: Leflunomide treatment (20 mg/d), placebo, or methotrexate treatment (7.5-15 mg/wk). MAIN OUTCOME MEASURES: American College of Rheumatology success rate (completed 52 weeks of treatment and met the ACR > or = 20% response criteria), disease progression as assessed by x-ray films, and improvement in function and health-related quality of life using the intent-to-treat population. RESULTS: The 482 patients studied were predominantly women (mean age, 54 years; mean disease duration, 6.7 years) for whom a mean of 0.8 disease-modifying antirheumatic drugs had failed. The ACR response and success rates for patients receiving leflunomide treatment (52% and 41%, respectively) and methotrexate treatment (46% and 35%, respectively) were significantly higher than those for patients receiving placebo (26% and 19%, respectively) (P<.001), and they were statistically equivalent, with mean time to initial response at 8.4 weeks for patients receiving leflunomide vs 9.5 weeks for patients receiving methotrexate therapy. X-ray analyses demonstrated less disease progression with leflunomide (P=.001) and methotrexate (P = .02) therapy than with placebo. Leflunomide and methotrexate treatment improved measures of physical function and health-related quality of life significantly more than placebo (P<.001 and P<.05, respectively). Common adverse events for patients receiving leflunomide treatment included gastrointestinal complaints, skin rash, and reversible alopecia. Asymptomatic transaminase elevations resulted in treatment discontinuations for 7.1% of patients receiving leflunomide therapy, 1.7% of patients receiving placebo, and 3.3% of patients receiving methotrexate therapy. CONCLUSIONS: Clinical responses following administration of leflunomide, a new therapeutic agent for the treatment of RA, were statistically superior to those with placebo and equivalent to those with methotrexate treatment. Both active treatments improved signs and symptoms of active RA, delayed disease progression as demonstrated by x-ray films, and improved function and health-related quality of life.

Adult↗
PubMed1996

Rizatriptan vs sumatriptan in the acute treatment of migraine. A placebo-controlled, dose-ranging study. Dutch/US Rizatriptan Study Group.

BACKGROUND: Rizatriptan (MK-462) is a new 5-hydroxytryptamine1D (serotonin1D; 5-HT1D) receptor agonist for the acute treatment of migraine that has improved pharmacokinetic properties compared with sumatriptan succinate. OBJECTIVE: To assess the efficacy and tolerability of 10-, 20-, and 40-mg doses of oral rizatriptan vs a 100-mg dose of oral sumatriptan succinate and placebo for the acute treatment of migraine. DESIGN: Randomized, double-blind, parallel-group, placebo-controlled, outpatient trial. SETTING: Ten US and 4 Dutch investigator centers. PATIENTS: Patients who had migraine with or without aura (N = 449). MAIN OUTCOME MEASURE: The proportion of patients whose conditions improved from severe or moderate headache immediately before dosing to mild or no headache at 2 hours after drug administration (ie, headache relief). RESULTS: The proportion of patients with headache relief was 18% for placebo; 46% for sumatriptan; and 52% for 10-mg, 56% for 20-mg, and 67% for 40-mg rizatriptan. All differences with placebo were statistically significant (P < .001), and 40-mg rizatriptan was superior to sumatriptan (P = .01). The proportion of patients who became free of pain at 2 hours was 3% for the placebo-treated group; 22% for the sumatriptan-treated group; and 26%, 35%, and 47% for the group of patients who took the 10-, 20-, and 40-mg doses of rizatriptan, respectively (all differences with placebo, P < .005; 40-mg rizatripan vs sumatriptan, P = .001). The recurrence of headache within 24 hours was found to be equal across all treatment groups-approximately 40%. Adverse events (most commonly short-lasting mild or moderate dizziness and drowsiness) occurred more frequently after a 40-mg dose of rizatriptan was given than after the other treatments. CONCLUSIONS: The antimigraine effect of 10- and 20-mg rizatriptan was superior to placebo, and comparable with that of 100-mg sumatriptan succinate; the efficacy of 40-mg rizatriptan was superior to that of both placebo and 100-mg sumatriptan succinate, although it was associated with a high frequency of adverse events.

Adult↗
PubMed1998

Efficacy and safety of acetaminophen, aspirin, and caffeine in alleviating migraine headache pain: three double-blind, randomized, placebo-controlled trials.

OBJECTIVE: To assess the effectiveness of the nonprescription combination of acetaminophen, aspirin, and caffeine in alleviating migraine headache pain. DESIGN: Three double-blind, randomized, parallel-group, single-dose, placebo-controlled studies. SETTING: Private practice, referral centers, and general community. PATIENTS: Migraineurs with moderate or severe headache pain who met International Headache Society diagnostic criteria for migraine with aura or without aura. The most severely disabled segment of migraineurs, including those whose attacks usually required bed rest, or who vomited 20% or more of the time, were excluded. Of the 1357 enrolled patients, 1250 took study medication and 1220 were included in the efficacy-evaluable data set. INTERVENTION: Two tablets of the nonprescription combination of acetaminophen, aspirin, and caffeine or placebo taken orally as a single-dose treatment of 1 eligible acute migraine attack. MAIN OUTCOME MEASURES: Pain intensity difference from baseline; percentage of patients with pain reduced to mild or none. RESULTS: Significantly greater reductions in migraine headache pain intensity 1 to 6 hours after dose were seen in patients taking the acetaminophen, aspirin, and caffeine combination than in those taking placebo in each of the 3 studies. Pain intensity was reduced to mild or none 2 hours after dose in 59.3% of the 602 drug-treated patients compared with 32.8% of the 618 placebo-treated patients (P< .001; 95% confidence interval [CI], 55%-63% for drug, 29%-37% for placebo); at 6 hours after dose, 79% vs 52%, respectively, had pain reduced to mild or none (P<.001; 95% CI, 75%-82% vs 48%-56%). In addition, by 6 hours after dose, 50.8% of the drug-treated patients were pain free compared with 23.5% of the placebo-treated patients (P<.001; 95% CI, 47%-55% for drug, 20%-27% for placebo). Other migraine headache characteristics, such as nausea, photophobia, phonophobia, and functional disability, were significantly improved 2 to 6 hours after treatment with the acetaminophen, aspirin, and caffeine combination compared with placebo (P< or =.01). CONCLUSIONS: The nonprescription combination of acetaminophen, aspirin, and caffeine was highly effective for the treatment of migraine headache pain as well as for alleviating the nausea, photophobia, phonophobia, and functional disability associated with migraine attacks. This drug combination also has an excellent safety profile and is well tolerated.

Acetaminophen↗
PubMed2006

Efficacy of duct tape vs placebo in the treatment of verruca vulgaris (warts) in primary school children.

OBJECTIVE: To determine the efficacy of duct tape compared with placebo in the treatment of verruca vulgaris. DESIGN AND SETTING: A randomized placebo-controlled trial in 3 primary schools in Maastricht, the Netherlands. PARTICIPANTS: One hundred three children aged 4 to 12 years with verruca vulgaris. INTERVENTIONS: Duct tape applied to the wart or placebo, a corn pad (protection ring for clavi), applied around the wart for 1 night a week. Both treatments were applied for a period of 6 weeks. Patients were blinded to the hypothesis of the study. MAIN OUTCOME MEASUREMENT: Complete resolution of the treated wart. RESULTS: After 6 weeks, the wart had disappeared in 16% of the children in the duct tape group compared with 6% in the placebo group (P = .12). The estimated effect of duct tape compared with placebo on diameter reduction of the treated wart was 1.0 mm (P = .02, 95% confidence interval, -1.7 to -0.1). After 6 weeks, in 7 children (21%) in the duct tape group, a surrounding wart had disappeared compared with 9 children (27%) in the placebo group (P = .79). Fifteen percent of the children in the duct tape group reported adverse effects such as erythema, eczema, and wounds compared with 0 in the placebo group (P = .14). CONCLUSION: In a 6-week trial, duct tape had a modest but nonsignificant effect on wart resolution and diameter reduction when compared with placebo in a cohort of primary school children.

Adhesives↗
PubMed2002

A randomized placebo-controlled trial of fluoxetine in body dysmorphic disorder.

BACKGROUND: Research on the pharmacotherapy of body dysmorphic disorder (BDD), a common and often disabling disorder, is limited. Available data suggest that this disorder may respond to serotonin reuptake inhibitors. However, no placebo-controlled treatment studies of BDD have been published. METHODS: Seventy-four patients with DSM-IV BDD or its delusional variant were enrolled and 67 were randomized into a placebo-controlled parallel-group study to evaluate the efficacy and safety of fluoxetine hydrochloride. After 1 week of single-blind placebo treatment, patients were randomized to receive 12 weeks of double-blind treatment with fluoxetine or placebo. Outcome measures included the Yale-Brown Obsessive Compulsive Scale Modified for Body Dysmorphic Disorder (BDD-YBOCS) (the primary outcome measure), the Clinical Global Impressions Scale, the Brown Assessment of Beliefs Scale, and other measures. RESULTS: Results of the BDD-YBOCS indicated that fluoxetine was significantly more effective than placebo for BDD beginning at week 8 and continuing at weeks 10 and 12 (F(1,64) = 16.5; P<.001). The response rate was 18 (53%) of 34 to fluoxetine and 6 (18%) of 33 to the placebo (chi(2)(1) = 8.8; P=.003). The BDD symptoms of delusional patients were as likely as those of nondelusional patients to respond to fluoxetine, and no delusional patients responded to the placebo. In the sample as a whole, treatment response was independent of the duration and severity of BDD and the presence of major depression, obsessive-compulsive disorder, or a personality disorder. Fluoxetine was generally well tolerated. CONCLUSION: Fluoxetine is safe and more effective than placebo in delusional and nondelusional patients with BDD.

Adult↗
PubMed1998

Effect of pentoxifylline in severe sepsis: results of a randomized, double-blind, placebo-controlled study.

OBJECTIVE: To evaluate the effect of pentoxifylline on organ dysfunction, survival, and mediator response in patients with severe sepsis. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Surgical intensive care units at 2 university hospitals. PATIENTS: Fifty-one surgical patients with severe sepsis were randomized to receive pentoxifylline continuously (27 patients) or saline infusion as placebo (24 patients). INTERVENTIONS: PATIENTS received pentoxifylline (1 mg/kg of body weight per hour; maximum, 1800 mg/d) during 28 days or until they were discharged from the intensive care unit or died. MEASUREMENTS AND MAIN RESULTS: Vital signs and organ function were determined at diagnosis; daily from day 1 to 7; on days 10, 14, 17, 21, and 24; and 28 days after diagnosis of sepsis. There were no differences in characteristics of patients at diagnosis in the Acute Physiology and Chronic Health Evaluation II (APACHE II) score (mean+/-SEM, 17+/-4 points for the pentoxifylline group and 18+/-5 points for the placebo group), the multiple organ dysfunction score (mean+/-SEM, 11.0+/-0.8 vs 11.8+/-1.0 points), tumor necrosis factor alpha and interleukin 6 bioactivity, serum endotoxin levels, or organ dysfunction. At study entrance, 23 of 27 patients in the pentoxifylline group and 21 of 24 patients in the placebo group experienced septic shock. No adverse effects of pentoxifylline treatment were observed. The 28-day mortality rate was 30% (8/27) in pentoxifylline-treated patients and 33% (8/24) in the placebo group. Hospital mortality was 41% (11/27) in the pentoxifylline group and 54% (13/24) in the placebo group. The multiple organ dysfunction score decreased in patients receiving pentoxifylline 4 days after diagnosis of sepsis compared with placebo-treated patients; a significant difference was reached on day 14 (P<.05; Student t test, Bonferoni correction). The PaO2/FIO2 (fraction of inspired oxygen) ratio was significantly improved in pentoxifylline-treated patients on days 14 and 17 (P<.05), and the pressure-adjusted heart rate was significantly improved on day 6 (P<.05) compared with the placebo group. Serum endotoxin levels, tumor necrosis factor alpha and interleukin 6 bioactivity were not different between the groups during the study. CONCLUSIONS: Continuous intravenous administration of pentoxifylline beneficially influenced cardiopulmonary dysfunction in patients with sepsis without adverse effects. Larger trials are needed to evaluate the efficacy in improving organ function in relation to the outcome for patients with severe sepsis.

APACHE↗
PubMed2006

Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial.

CONTEXT: The alpha4beta2 nicotinic acetylcholine receptors (nAChRs) are linked to the reinforcing effects of nicotine and maintaining smoking behavior. Varenicline, a novel alpha4beta2 nAChR partial agonist, may be beneficial for smoking cessation. OBJECTIVE: To assess efficacy and safety of varenicline for smoking cessation compared with sustained-release bupropion (bupropion SR) and placebo. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, parallel-group, placebo- and active-treatment-controlled, phase 3 clinical trial conducted at 19 US centers from June 19, 2003, to April 22, 2005. Participants were 1025 generally healthy smokers (> or =10 cigarettes/d) with fewer than 3 months of smoking abstinence in the past year, 18 to 75 years old, recruited via advertising. INTERVENTION: Participants were randomly assigned in a 1:1:1 ratio to receive brief counseling and varenicline titrated to 1 mg twice per day (n = 352), bupropion SR titrated to 150 mg twice per day (n = 329), or placebo (n = 344) orally for 12 weeks, with 40 weeks of nondrug follow-up. MAIN OUTCOME MEASURES: Primary outcome was the exhaled carbon monoxide-confirmed 4-week rate of continuous abstinence from smoking for weeks 9 through 12. A secondary outcome was the continuous abstinence rate for weeks 9 through 24 and weeks 9 through 52. RESULTS: For weeks 9 through 12, the 4-week continuous abstinence rates were 44.0% for varenicline vs 17.7% for placebo (odds ratio [OR], 3.85; 95% confidence interval [CI], 2.70-5.50; P<.001) and vs 29.5% for bupropion SR (OR, 1.93; 95% CI, 1.40-2.68; P<.001). Bupropion SR was also significantly more efficacious than placebo (OR, 2.00; 95% CI, 1.38-2.89; P<.001). For weeks 9 through 52, the continuous abstinence rates were 21.9% for varenicline vs 8.4% for placebo (OR, 3.09; 95% CI, 1.95-4.91; P<.001) and vs 16.1% for bupropion SR (OR, 1.46; 95% CI, 0.99-2.17; P = .057). Varenicline reduced craving and withdrawal and, for those who smoked while receiving study drug, smoking satisfaction. No sex differences in efficacy for varenicline were observed. Varenicline was safe and generally well tolerated, with study drug discontinuation rates similar to those for placebo. The most common adverse events for participants receiving active-drug treatment were nausea (98 participants receiving varenicline [28.1%]) and insomnia (72 receiving bupropion SR [21.9%]). CONCLUSION: Varenicline was significantly more efficacious than placebo for smoking cessation at all time points and significantly more efficacious than bupropion SR at the end of 12 weeks of drug treatment and at 24 weeks. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00141206.

Adult↗
PubMed2006

Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial.

CONTEXT: Varenicline, a partial agonist at the alpha4beta2 nicotinic acetylcholine receptor, has the potential to aid smoking cessation by relieving nicotine withdrawal symptoms and reducing the rewarding properties of nicotine. OBJECTIVE: To determine the efficacy and safety of varenicline for smoking cessation compared with placebo or sustained-release bupropion (bupropion SR). DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled trial conducted between June 2003 and March 2005 at 14 research centers with a 12-week treatment period and follow-up of smoking status to week 52. Of 1413 adult smokers who volunteered for the study, 1027 were enrolled; 65% of randomized participants completed the study. INTERVENTION: Varenicline titrated to 1 mg twice daily (n = 344) or bupropion SR titrated to 150 mg twice daily (n = 342) or placebo (n = 341) for 12 weeks, plus weekly brief smoking cessation counseling. MAIN OUTCOME MEASURES: Continuous abstinence from smoking during the last 4 weeks of treatment (weeks 9-12; primary end point) and through the follow-up period (weeks 9-24 and 9-52). RESULTS: During the last 4 weeks of treatment (weeks 9-12), 43.9% of participants in the varenicline group were continuously abstinent from smoking compared with 17.6% in the placebo group (odds ratio [OR], 3.85; 95% confidence interval [CI], 2.69-5.50; P<.001) and 29.8% in the bupropion SR group (OR, 1.90; 95% CI, 1.38-2.62; P<.001). For weeks 9 through 24, 29.7% of participants in the varenicline group were continuously abstinent compared with 13.2% in the placebo group (OR, 2.83; 95% CI, 1.91-4.19; P<.001) and 20.2% in the bupropion group (OR, 1.69; 95% CI, 1.19-2.42; P = .003). For weeks 9 through 52, 23% of participants in the varenicline group were continuously abstinent compared with 10.3% in the placebo group (OR, 2.66; 95% CI, 1.72-4.11; P<.001) and 14.6% in the bupropion SR group (OR, 1.77; 95% CI, 1.19-2.63; P = .004). Treatment was discontinued due to adverse events by 10.5% of participants in the varenicline group, 12.6% in the bupropion SR group, and 7.3% in the placebo group. The most common adverse event with varenicline was nausea, which occurred in 101 participants (29.4%). CONCLUSIONS: Varenicline is an efficacious, safe, and well-tolerated smoking cessation pharmacotherapy. Varenicline's short-term and long-term efficacy exceeded that of both placebo and bupropion SR. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00143364.

Adult↗
PubMed1998

A placebo-controlled, double-blind trial of the long-term effects of albuterol administration in patients with cystic fibrosis.

This placebo-controlled study was designed to confirm a previously performed open label study that showed significant improvement in spirometry on maintenance therapy with albuterol for 1 year. In a double-blind, cross-over trial, albuterol (by metered dose inhaler) 180 microg b.i.d. or placebo were given for 6 months each. Spirometry was monitored at the start, and 3 and 6 months following initiation of each arm of the study. Peak expiratory flow rate (PEFR) was measured twice daily at home before and after study drug administration. Only patients with clinically detectable lung disease were enrolled. Twenty-one patients finished the study. All spirometric tests showed a significant improvement from start to end of the 6 month treatment with albuterol; there was no significant change on placebo. Forced vital capacity improved by 8.2% and forced expiratory volume in 1 s by 12.1% on albuterol therapy. Nevertheless, there was no significant difference between change on albuterol and change on placebo. Home measurements of PEFR showed a significant improvement of 4.7% on albuterol and a non-significant change of 2.0% on placebo from the first to the last week of treatment. None of the long-term improvements (spirometry or home PEFR) correlated with mean daily bronchodilation. For albuterol, the number of days of hospitalization was less than half that for patients on placebo (1.0/patient on albuterol versus 2.6 on placebo), but this did not reach statistical significance. These results suggest a beneficial effect from maintenance therapy with albuterol. Bronchodilation alone probably cannot explain the long-term benefits of albuterol, and other mechanisms may play a role. The lack of significant difference between change on albuterol and change on placebo is probably due to too small a number of patients in this study and lack of statistical power.

Administration, Inhalation↗