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At least 451 records · Page 25Linked to original sources
PubMed2005

A randomized, double-blind, placebo-controlled efficacy and safety study of quetiapine or lithium as monotherapy for mania in bipolar disorder.

OBJECTIVE: To evaluate the efficacy and tolerability of quetiapine monotherapy versus placebo for the treatment of mania associated with bipolar disorder. METHOD: In an international, multicenter, double-blind, parallel-group, 12-week study, patients with a DSM-IV diagnosis of bipolar I disorder (manic episode) were randomly assigned to treatment with quetiapine (flexibly dosed up to 800 mg/day), placebo, or lithium. The primary efficacy measure was change from baseline in Young Mania Rating Scale (YMRS) score at day 21. Data were gathered from April 2001 to May 2002. RESULTS: More patients in the quetiapine (72/107) and lithium (67/98) groups completed the study compared with the placebo group (35/97). Improvement (reduction) in YMRS score was significantly greater for quetiapine than placebo at day 7 (-8.03 vs. -4.89; p < .01), and the difference between groups continued to increase over time to day 21 (-14.6 vs. -6.7; p < .001) and to endpoint at day 84 (-20.3 vs. -9.0; p < .001). Significantly more quetiapine patients compared with placebo patients fulfilled YMRS response criteria at day 21 (53.3% vs. 27.4%; p < .001) and at day 84 (72.0% vs. 41.1%; p < .001). Quetiapine was also superior to placebo in efficacy at day 21 and day 84 by all secondary measures. Lithium-treated patients improved significantly compared with placebo patients and similarly to quetiapine-treated patients on the primary efficacy measure. The most common adverse events for quetiapine were dry mouth, somnolence, and weight gain, while lithium was associated with tremor and insomnia. The quetiapine and placebo groups had similar, low levels of extrapyramidal symptom-related adverse events. CONCLUSIONS: Quetiapine demonstrated superior efficacy to placebo in patients with bipolar mania and was well tolerated.

Adolescent↗
PubMed2006

Duloxetine efficacy for major depressive disorder in male vs. female patients: data from 7 randomized, double-blind, placebo-controlled trials.

OBJECTIVE: A number of studies have suggested potential gender differences in the efficacy of antidepressant medications. Pooled data from double-blind, placebo-controlled studies were utilized to compare the efficacy of duloxetine in the treatment of major depressive disorder (MDD) in male and female patients. METHOD: Efficacy data were pooled from 7 randomized, double-blind, placebo-controlled clinical trials of duloxetine. These studies represent all available data from U.S. acute-phase, placebo-controlled studies of duloxetine for the treatment of MDD. Patients (aged > or = 18 years) meeting DSM-IV criteria for MDD received duloxetine (40-120 mg/day; men, N = 318; women, N = 578) or placebo (men, N = 242; women, N = 484) for up to 9 weeks. Efficacy measures included the 17-item Hamilton Rating Scale for Depression (HAM-D17) total score, HAM-D17 subscales (core, Maier, anxiety, retardation, sleep), the Clinical Global Impressions-Severity of Illness scale (CGI-S) and Patient Global Impression of Improvement scale (PGI-I), the Quality of Life in Depression Scale (QLDS), and Visual Analog Scales (VAS) for pain. The first patient visit was February 1, 1999, and the last patient visit was November 27, 2002. RESULTS: In both male and female patients, duloxetine produced significantly greater improvement in HAM-D17, CGI-S, and PGI-I when compared with placebo (p < .05). Treatment-by-gender interactions did not reach statistical significance, indicating that the magnitude of duloxetine's treatment effects did not differ significantly between male and female patients. However, there was a trend for female patients to show a more robust response than male patients to both duloxetine and placebo. On the basis of VAS assessments of pain severity, duloxetine-treated female patients appeared to exhibit greater improvement than male patients, while women receiving placebo had smaller responses than placebo-treated men. Improvements in quality of life were significantly greater for both men (p = .006) and women (p = .001) receiving duloxetine than placebo and showed no significant difference by gender. CONCLUSION: In this analysis of pooled data, the efficacy of duloxetine did not differ significantly in male and female patients.

Adolescent↗
PubMed2002

Significant differential effects of alendronate, estrogen, or combination therapy on the rate of bone loss after discontinuation of treatment of postmenopausal osteoporosis. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Combination therapy with alendronate and estrogen for 2 years increases bone mineral density at the spine and hip more than does therapy with either agent alone. Changes in bone mineral density after discontinuation of therapy have not been compared directly. OBJECTIVE: To determine the rate of bone loss when therapy with alendronate, estrogen, or both agents is discontinued. DESIGN: Double-blind, placebo-controlled discontinuation trial. SETTING: 18 U.S. centers. PATIENTS: 244 postmenopausal, hysterectomized women 44 to 77 years of age. INTERVENTION: 2 years of therapy with alendronate, 10 mg/d (n = 92); conjugated estrogen, 0.625 mg/d (n = 143); alendronate and conjugated estrogen (n = 140); or placebo (n = 50). At year 3, women were allocated into five groups: Twenty-eight women continued to take placebo and 44 women continued to take combination therapy, but 50 women taking alendronate, 81 taking conjugated estrogen, and 41 taking combination therapy were switched to placebo. MEASUREMENTS: Bone mineral density and biochemical markers of bone turnover. RESULTS: Women taking alendronate or combination therapy who were switched to placebo for year 3 of the study maintained bone mass. Bone mineral density in these women was 4.1% (CI, 2.6% to 5.7%) and 6.6% (CI, 5.0% to 8.2%) higher, respectively, at the spine (P < 0.001 for both treatment comparisons) and 3.5% (CI, 2.3% to 4.6%) and 3.0% (CI, 1.8% to 4.2%) higher, respectively, at the trochanter (P < 0.001 for both treatment comparisons) than that in women previously taking estrogen who were switched to placebo. In contrast, women who were taking estrogen and were switched to placebo during year 3 experienced a 4.5% decrease at the spine (95% CI, -5.0% to -4.0%) and a 2.4% decrease at the trochanter (CI, -2.7% to -2.1%) (P < 0.001 for both changes). Compared with women who took placebo for 3 years, women who took estrogen for 2 years and were then switched to placebo had a bone mineral density that was 2.9% higher (CI, 1.2% to 4.6%) at the spine (P < 0.05) and 2.9% higher (CI, 1.6% to 4.2%) at the trochanter (P < 0.001). Changes in biochemical markers during year 3 did not differ among the groups that discontinued active treatment. CONCLUSIONS: Accelerated bone loss is seen after withdrawal of estrogen therapy but not after withdrawal of alendronate or combination therapy. The differential effects after withdrawal of therapy should be considered in the management of postmenopausal osteoporosis.

Adult↗
PubMedDate not supplied

The placebo response in Parkinson's disease. Parkinson Study Group.

Our objective was to study the placebo response in Parkinson's disease (PD). We conducted a literature search in which placebo response was measured in all studies of PD from 1969 to April 1996. Strict criteria were defined to include or exclude published reports in our survey. The Parkinson Study Group database for Deprenyl & Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) was reviewed and placebo "responders" were compared to placebo "nonresponders" by age, race, religion, level of education, duration of PD, and gender. A significant difference between the efficacy of placebo and that of active drug was reported in 61% (22 of 36) of the articles meeting the required criteria; DATATOP analysis showed no statistically significant epidemiologic differences between 140 placebo responders and 58 placebo nonresponders except in PD effect on current job. Although there is clearly a placebo response in PD patients, our review suggests that the variation in placebo response does not correlate with demographic factors such as age, gender, religion, level of education, or duration of PD.

Female↗
PubMed2001

Perimenopausal women in estrogen vasomotor trials: contribution to placebo effect and efficacy outcome.

OBJECTIVE: To determine the difference, if any, in the placebo response when both perimenopausal and postmenopausal women are enrolled, compared with postmenopausal women alone, in a study assessing the efficacy of synthetic conjugated estrogen tablets on moderate-to-severe vasomotor symptoms (MSVS). METHODS: A total of 120 healthy women (72 active; 48 placebo) complaining of moderate-to-severe vasomotor symptoms were enrolled in a randomized, placebo-controlled, double-blind, multicenter clinical trial. In all, 109 patients completed treatment to week 12. Women were enrolled using minimal inclusion and exclusion criteria, and included perimenopausal women (n = 34; 0 to 6 months since last menses) as well as menopausal women (n = 79; > 12 months since last menses). RESULTS: Changes in MSVS in the intent-to-treat (ITT) population showed differences between the active and placebo treatments at weeks 4 (p < 0.022), 8 (p < 0.010) and 12 (p < 0.010). At week 12, the mean percentage reduction in MSVS was 81% for the active treatment group and 58% in the placebo treatment group. To examine the placebo response, the ITT population was broken down into groups defined by the time since their last menses. The perimenopausal group (0 to 6 months since last menses) demonstrated a consistently higher placebo response than that of the postmenopausal groups (> 12 months since last menses). CONCLUSIONS: Perimenopausal women contributed to a higher placebo response, compared with the rate of response previously reported in clinical studies of estrogen replacement in postmenopausal women. Including perimenopausal women in future vasomotor symptom trials will require study populations of sufficient size to maintain the statistical power to demonstrate a difference between therapeutic response to active or placebo treatment.

Administration, Oral↗
PubMed2001

[Influence of placebo effect on planning and analysis of clinical trials].

Placebos, seen as any pharmacological procedure without a specific effect, have been widely used in medical practice. In the fifties, when clinical trial development started, placebos assume a new dimension, as fundamental tools in clinical trial design. The aim of this review was to evaluate and describe methodological aspects related to placebo use in clinical trials. Despite the importance attributed to placebos, particularly to maintain blinding, it is not always easy to simulate an active procedure. On the other hand, the ethical aspects of placebo utilization in some clinical and experimental circumstances are becoming more and more complex. These two aspects are commented. It is emphasized that the use of a placebo, by itself, may influence the results of a clinical study. We analyze the factors that determine the placebo effect but also how placebos and the placebo effect affect final results.

Clinical Trials as Topic↗
PubMedDate not supplied

[The difficulty of measurement of placebo effect].

The use of placebos within controlled clinical trials for the placebo effect; last 50 years suggests that psycho-physiological effects can be objectified and measured. These are related to the therapeutic measurement; results covered by the term "placebo effect". Since Beecher's pioneer article in 1955, this effect is recognised and cited in randomised clinical trial; medical articles as being on average 35% effective on the majority of symptoms. However, the meaning of these measurement artefact is questionable. For example, it does not take into account the spontaneous evolution of symptoms and diseases. In fact, the placebo effect is not the effect measured in the group treated by the placebo. The clinical trial drug controlled against placebo does not make it possible to measure what is thus wrongly called "the placebo effect". Is it possible then to measure and to objectify what is called the placebo effect? And if that is possible, how? This article calls into question the extent of the placebo effect evaluated by means of controlled clinical trials, without denying its importance in medical practice. Firstly it raises the epistemological problem of the real possibility, via experimentation, of objectifying psychological therapeutic effects. And secondly, the question is also raised of the interest for medical care of objectifying those effects.

Clinical Trials as Topic↗
PubMed1990

Buspirone in the management of major depression: a placebo-controlled comparison.

One hundred forty outpatients with major depression were admitted to an 8-week, placebo-controlled, double-blind study of buspirone. Entry criteria included a Hamilton Rating Scale for Depression (25-item [HAM-D]) score of greater than or equal to 18 and a Hamilton Rating Scale for Anxiety (HAM-A), score of greater than or equal to 18. A flexible dose schedule ranging from 5-90 mg/day was employed. The mean dose of buspirone was 41-54 mg/day from Week 2 to the end of the study. Sixty-four percent of buspirone patients and 50% of placebo patients were melancholic; 64% of buspirone patients and 74% of placebo patients discontinued treatment before the end of the study. Extender data analysis showed that buspirone patients had significant (p less than .05) HAM-D score reductions compared with the placebo group at Weeks 2, 3, 4, and 6. The HAM-D retardation factor trended toward significance over placebo at Weeks 3, 4, and 6. HAM-D change scores for the subgroup of melancholic patients taking buspirone were significantly (p less than .02) better than those of the placebo-treated melancholic subjects at Weeks 2, 3, 4, and 6. Most other efficacy parameters also favored the buspirone-treated group over the placebo-treated group. The most common adverse experiences for the buspirone group were CNS effects (74% in the buspirone group vs. 21% in the placebo group) and gastrointestinal effects (55% in the buspirone group vs. 37% in the placebo group). Side effects consisted of dizziness, light-headedness, nausea, and headache. No serious or unexpected adverse effects occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Double-blind, placebo-controlled trial comparing long-term suppressive with short-term oral acyclovir therapy for management of recurrent genital herpes.

A total of 156 patients with frequently recurring genital herpes were enrolled in a randomized, double-blind, one-year trial comparing long-term suppressive and intermittent oral acyclovir therapy with placebo in the management of recurrent genital herpes. Subjects received either suppressive treatment with acyclovir, 400 mg twice daily for one year, and 200 mg five times per day for five days, for short-term treatment of recurrences; intermittent treatment with placebo, twice daily for one year, and oral acyclovir, 200 mg five times per day for five days, for short-term treatment of recurrences; or treatment with placebo, twice daily for one year, and five times per day for five days for short-term treatment of recurrences. Median time to first recurrence was 250 days for the suppressive group, 28 days for the intermittent group, and 23 days for the placebo group (p = 0.001). The median number of days per month with active disease was 0.32 for the suppressive group, 4.18 for the intermittent group, and 4.72 for the placebo group (p less than 0.001), with a median recurrence rate per 30-day treatment period of 0.08 recurrences/patient in the suppressive group, 0.70 in the intermittent group, and 0.74 in the placebo group (p less than 0.001). Median duration of recurrence was 5.0 days in the suppressive group compared with 6.0 days in the combined intermittent acyclovir plus placebo group (p = 0.001), and was reduced from 7.0 to 6.0 days when intermittent acyclovir treatment was compared with placebo treatment (p = 0.05). Daily administration of oral acyclovir for one year is superior to intermittent or placebo treatment in the management of patients with frequently recurring genital herpes.

Acyclovir↗
PubMed1987

[The placebo: beyond pretense and the nuisance variable. Arguments in favor of re-evaluating a significant protherapeutic concept ("aura curae")].

In this theoretical paper the concept of placebo is being investigated within a field of tension: on one side the conventional understanding of "placebo", that is empirically inconsistent and scientifically and ethically unsatisfactory, and on the other side the upgraded concept of "aura curae" as suggested by the author, that appears to be less contradictory and also richer in heuristic potential and, conceivably, may be closer to the essence of "placebo" itself. This statement is being corroborated by six main arguments. The first three arguments are meant to weaken the conventional concept of "placebo": The first argument deals with the empirical inconsistencies of the traditional placebo concept; the second addresses the possible distortion of scientific conclusions drawn from a conventional "placebo-controlled" trial; the third argument deals with the ethical problems of "pretense" and of "withholding adequate medication". The following three corresponding arguments are put forward in support of the upgraded placebo-concept of "aura curae" (Latin: "air of care"; "unspecific healing context"). The fourth argument introduces the concept of "aura curae" itself; the fifth argument deals with two alternatives to the conventional placebo-controlled trial, namely the "placebo-integration" and the "value added efficacy"; the sixth argument concludes with a discussion of the ethical advantages of implementing the concept of "aura curae" in clinical and research practice. The purpose of this paper is to contribute to a comprehensive "healing context", that would better fit the patient's needs; i.e., in addition to the various traditional "therapies" of specific influence (biological and psychosocial), the "protherapeutic" and unspecific effects of the "aura curae" should be integrated into a systemic patient care.

Clinical Trials as Topic↗
PubMed1984

Placebo-controlled clinical trials in gastroenterology. A position paper of the American College of Gastroenterology.

Treatment programs for digestive diseases should be evaluated by randomized clinical trials. Under most circumstances, the best design for such trials requires placebo controls. For example, clinical trials should include groups of placebo-treated patients when there is no commonly accepted standard patients when there is no commonly accepted standard therapy for the disease under study, when standard therapy is of doubtful efficacy, or when standard therapy is unacceptably toxic. Moreover, illnesses--including peptic ulcer and IBD--may have sufficiently high response rates to placebo therapy as to favor placebo-controlled study designs. Placebo treatment is also free of substantial risk, at least compared to active drug treatment, when the disease process is very mild or when the study period is very short. Acceptable alternatives to placebo control include direct comparisons of new agents to standard therapy and addition of either new agents or placebo to a continuing baseline of standard therapy. Similarly, both placebo and active-treatment groups can sometimes be permitted access to standard therapy on a p.r.n. basis, with utilization thereof serving as one of the criteria of therapeutic response. Placebo-controlled trials are therefore generally feasible and desirable methods for testing the safety and efficacy of various proposed treatments for gastrointestinal diseases. High ethical standards in clinical medicine depend on high scientific standards in clinical research.

Clinical Trials as Topic↗
PubMed1981

[The status of placebo treatment in a psychiatric hospital (author's transl)].

The placebo treatments at the Rheinische Landes- und Hochschulklinik für Psychiatrie Essen were registered during one year. With interviews and nurses' reports indication, situation, and supposed effect were inquired. A questionnaire investigated the therapists' and nursing staff's attitudes towards the therapy with placebos. 3,9% of the masculine and 6,1% of the feminine patients were treated with placebos without preference of an age or a group of diagnoses. Placebos were predominantly prescribed for concomitant symptoms of psychiatric diseases (especially complaints of sleep disorders or pain). Mostly placebos were taken in case of abuse, forceful lamentation, and assumption of physical complaints without an organic basis. The nursing staff often administered placebos without agreement of the doctor to avoid calling him at night. Between and within the professional groups there were marked differences in the attitudes towards placebos. Besides these results some problems of the use and outcome control of placebos are discussed. On the whole reserve in the medication of placebos is recommended.

Adult↗
PubMed1994

Platelet-activating factor receptor antagonist BN 52021 in the treatment of severe sepsis: a randomized, double-blind, placebo-controlled, multicenter clinical trial. BN 52021 Sepsis Study Group.

OBJECTIVE: To evaluate the safety and efficacy of a natural platelet-activating factor receptor antagonist, BN 52021 (Ginkgolide B), in the treatment of patients with sepsis syndrome. DESIGN: Prospective, randomized, placebo-controlled, double-blind, phase III, multicenter clinical trial. SETTING: Twenty-one academic medical center intensive care units in France. PATIENTS: Two hundred sixty-two patients with sepsis syndrome who received standard supportive care and antimicrobial therapy, in addition to the administration of platelet-activating factor receptor antagonist or placebo. INTERVENTIONS: Patients received either a 120-mg dose of platelet-activating factor receptor antagonist intravenously every 12 hrs over a 4-day period or placebo. MAIN OUTCOME MEASUREMENTS: All patients were evaluated for 28-day, all-cause mortality. RESULTS: The 28-day mortality rate was 51% for the placebo group and 42% for the platelet-activating factor receptor antagonist group (p = .17). However, the efficacy of platelet-activating factor receptor antagonist was significantly greater in patients with Gram-negative sepsis (test for interaction, p = .03). In a separate analysis of patients with and without Gram-negative sepsis, the 28-day mortality rate was 57% for the patients receiving placebo (30 deaths of 53 patients) and 33% for patients receiving platelet-activating factor receptor antagonist (22 deaths of 67 patients; p = .01). Platelet-activating factor receptor antagonist also significantly (p = .01) reduced the mortality rate among patients with Gram-negative sepsis who were in shock at entry into the study (mortality rate was 65% for placebo vs. 37% for platelet-activating factor receptor antagonist) and among patients > 60 yrs of age (mortality rate was 74% for placebo vs. 31% for platelet-activating factor receptor antagonist). A Cox proportional-hazards model identified five independent prognostic factors: a) adequacy of antibiotic therapy; b) severity of illness; c) renal failure; d) hematologic failure; and e) hepatic failure at study entry. When the Gram-negative sepsis population was stratified by age and these five prognostic factors were controlled for, the relative risk of death of the platelet-activating factor receptor antagonist group was 0.61 (0.34 to 1.08, 95% confidence interval; p = .09). This risk corresponds with an adjusted reduction in mortality rate of 39% for patients receiving platelet-activating factor receptor antagonist. No differences in mortality rates were found between the placebo and the platelet-activating factor receptor antagonist groups in the absence of Gram-negative sepsis. There were no differences in adverse events between the placebo and the treated groups. CONCLUSION: The studied platelet-activating factor receptor antagonist (BN 52021) seems to be a safe and promising treatment for patients with severe Gram-negative sepsis.

APACHE↗
PubMed1977

Placebo and its importance in medicine.

Placebo can be defined as "a therapeutic effect, drug or non-drug, or a part of it which, in the condition being treated, objectively does not have any specific pharmacodynamic action." Even today when powerful drugs are available placebo is important and present in therapy. Effective therapeutic agents are also sometimes used as placebo, mostly inadvertently. In clinical pharmacological investigations placebos are used deliberately to discriminate the pharmacodynamic action of drugs from psychic and other factors which can influence the objective of the drug evalution. The use of placebo in therapeutic trials is justified only when no effective treatment is available or the symptom or disease is trivial. Placebo effect is especially pronounced in diseases where pain is an important symptom as well as in psychosomatic diseases. The extent of placebo reaction depends on patient's characteristics (reactors and non-reactors), drug presentation, as well as on personality and attitudes of the prescriber. Deliberate use of placebo other than in clinical therapeutic investigation is justified in mild mental depression and in situations where the diagnosis is known, no drug is necessary, but the patient's pressure to get a prescription is irresistible (?). Every doctor should cultivate the induction of placebo reaction in treatment of his patient, but not to the extent that the belief of the former in the action of an inactive medication starts.

Ethics, Medical↗
PubMedDate not supplied

Smoking cessation with varenicline, a selective alpha4beta2 nicotinic receptor partial agonist: results from a 7-week, randomized, placebo- and bupropion-controlled trial with 1-year follow-up.

BACKGROUND: Currently available smoking cessation therapies have limited success rates. Varenicline tartrate is a novel, selective nicotinic receptor partial agonist developed specifically for smoking cessation. This study evaluated the efficacy, tolerability, and safety of 3 varenicline doses for smoking cessation. Bupropion hydrochloride was included as an active control. METHODS: A phase 2, multicenter, randomized, double-blind, placebo-controlled study of healthy smokers (18-65 years old). Subjects were randomized to varenicline tartrate, 0.3 mg once daily (n = 128), 1.0 mg once daily (n = 128), or 1.0 mg twice daily (n = 127), for 6 weeks plus placebo for 1 week; to 150-mg sustained-release bupropion hydrochloride twice daily (n = 128) for 7 weeks; or to placebo (n = 127) for 7 weeks. RESULTS: During the treatment phase, the continuous quit rates for any 4 weeks were significantly higher for varenicline tartrate, 1.0 mg twice daily (48.0%; P<.001) and 1.0 mg once daily (37.3%; P<.001), than for placebo (17.1%). The bupropion rate was 33.3% (P = .002 vs placebo). The carbon monoxide-confirmed continuous quit rates from week 4 to week 52 were significantly higher in the varenicline tartrate, 1.0 mg twice daily, group compared with the placebo group (14.4% vs 4.9%; P = .002). The bupropion rate was 6.3% (P = .60 vs placebo). Discontinuation owing to treatment-emergent adverse events was 15.9% for bupropion, 11.2% to 14.3% for varenicline, and 9.8% for placebo. No dose-related increases occurred in adverse events for varenicline. CONCLUSIONS: Varenicline tartrate demonstrated both short-term (1 mg twice daily and 1 mg once daily) and long-term efficacy (1 mg twice daily) vs placebo. Varenicline was well tolerated and may provide a novel therapy to aid smoking cessation.

Adolescent↗
PubMed2003

Analysis of outcome in retrieved dropout patients in a rivastigmine vs placebo, 26-week, Alzheimer disease trial.

BACKGROUND: Treatment with cholinesterase inhibitors improves cognition in patients with Alzheimer disease (AD). In studies designed with a washout period at the end of the study, after treatment with a cholinesterase inhibitor is discontinued, the cognitive benefits of therapy are no longer apparent following washout. The rivastigmine trials discussed in this article were not designed with a posttreatment washout period at the end of the study. Therefore, to evaluate the effect of discontinuing treatment, we analyzed the retrieved dropout (RDO) population. OBJECTIVE: To evaluate the change in cognition (at week 26 vs baseline) observed in patients from 3 large clinical trials of AD who prematurely discontinued treatment with placebo or rivastigmine. DESIGN AND METHODS: Eligible patients with AD (Mini-Mental State Examination [MMSE] score, 10-26, inclusive) were enrolled in 1 of three 26-week, double-blind, placebo-controlled studies (Novartis US Pivotal [dose-range] Trial, US fixed-dose study, and a Global Pivotal [dose-range] Trial) that compared rivastigmine therapy with placebo. Patients who discontinued study participation (for any reason) (considered to be the RDO population) were encouraged to return for their scheduled week 26 efficacy evaluations. Effects on cognition were assessed using the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog). RESULTS: The results for the Novartis US Pivotal Trials and for the 3 studies combined (Novartis studies B352, B351, and B303) are reported. In the US pivotal trial, RDO patients in the 6- to 12-mg/d group had been not receiving the drug (to be called "off drug") for 102 (57.7) days (mean [SD]) compared with 68 (51.7) days in the RDO placebo group. In these RDO analyses, a statistically significantly greater worsening on the ADAS-Cog mean change score was observed in the placebo group (n = 17) compared with the rivastigmine 6- to 12-mg/d group (n = 33) at week 26 (MMSE score, -8.2 vs -3.0; P =.009). In the pooled studies, the mean (SD) number of days off treatment was 95 (52.0) days for the rivastigmine 6- to 12-mg/d group and 66 (52.7) days for the placebo group. The RDO analysis also showed a statistically significantly greater decline in cognitive function as measured by the ADAS-Cog mean change score in the placebo group (n = 38) compared with the rivastigmine 6- to 12-mg/d group (n = 88) at week 26 (MMSE score, -5.69 vs -2.5; P =.004). A significantly greater proportion of patients in the placebo group exhibited at least a 4-point and 7-point worsening in ADAS-Cog scores at week 26 compared with the rivastigmine 6- to 12-mg/d group in both the Novartis US Pivotal Trials (P =.007, P =.009) and the pooled studies (P =.002, P =.017). CONCLUSIONS: After discontinuation of therapy, rivastigmine-treated patients exhibited less deterioration in cognitive function compared with placebo-treated patients. The less severe worsening of cognition after withdrawal of treatment in patients previously treated with rivastigmine suggests an effect on disease progression.

Adult↗
PubMed2005

A randomized, double-blind, placebo-controlled trial of pramipexole, a dopamine agonist, in patients with fibromyalgia receiving concomitant medications.

OBJECTIVE: To assess the efficacy and safety of pramipexole, a dopamine 3 receptor agonist, in patients with fibromyalgia. METHODS: In this 14-week, single-center, double-blind, placebo-controlled, parallel-group, escalating-dose trial, 60 patients with fibromyalgia were randomized 2:1 (pramipexole:placebo) to receive 4.5 mg of pramipexole or placebo orally every evening. The primary outcome was improvement in the pain score (10-cm visual analog scale [VAS]) at 14 weeks. Secondary outcome measures were the Fibromyalgia Impact Questionnaire (FIQ), the Multidimensional Health Assessment Questionnaire (MDHAQ), the pain improvement scale, the tender point score, the 17-question Hamilton Depression Inventory (HAM-d), and the Beck Anxiety Index (BAI). Patients with comorbidities and disability were not excluded. Stable dosages of concomitant medications, including analgesics, were allowed. RESULTS: Compared with the placebo group, patients receiving pramipexole experienced gradual and more significant improvement in measures of pain, fatigue, function, and global status. At 14 weeks, the VAS pain score decreased 36% in the pramipexole arm and 9% in the placebo arm (treatment difference -1.77 cm). Forty-two percent of patients receiving pramipexole and 14% of those receiving placebo achieved > or =50% decrease in pain. Secondary outcomes favoring pramipexole over placebo included the total FIQ score (treatment difference -9.57) and the percentages of improvement in function (22% versus 0%), fatigue (29% versus 7%), and global (38% versus 3%) scores on the MDHAQ. Compared with baseline, some outcomes showed a better trend for pramipexole treatment than for placebo, but failed to reach statistical significance, including improvement in the tender point score (51% versus 36%) and decreases in the MDHAQ psychiatric score (37% versus 28%), the BAI score (39% versus 27%), and the HAM-d score (29% versus 9%). No end points showed a better trend for the placebo arm. The most common adverse events associated with pramipexole were transient anxiety and weight loss. No patient withdrew from the study because of inefficacy or an adverse event related to pramipexole. CONCLUSION: In a subset of patients with fibromyalgia, approximately 50% of whom required narcotic analgesia and/or were disabled, treatment with pramipexole improved scores on assessments of pain, fatigue, function, and global status, and was safe and well-tolerated.

Adult↗
PubMed1990

The safety of anistreplase from the placebo-controlled AIMS study (anistreplase Intervention Mortality Study). The AIMS Study Group.

In the anistreplase, or anisoylated plasminogen streptokinase activator complex (APSAC) Intervention Mortality Study (AIMS), 1,258 patients with acute myocardial infarction were randomized in a parallel, double-blind, placebo-controlled mortality study in which they received either anistreplase or placebo, followed by anticoagulation therapy. Data on all adverse clinical events were recorded, regardless of their clinical significance or possible relation to therapy. There was a similar frequency of such events in both groups (anistreplase 80.4%, placebo 76.0%, difference not significant). Cardiovascular events included more reports of bradycardia, idioventricular rhythm, and hypotension in the anistreplase group, and a higher incidence of cardiac arrest, ventricular fibrillation, complete heart block, and pericarditis in the placebo group. Hemorrhagic events occurred in 13.8% of patients in the anistreplase group compared with 4.1% of patients in the placebo group. Most of these events consisted of bleeding or bruising around the puncture sites. There was a low incidence of allergic events after administration of both anistreplase and placebo. Thirteen cerebrovascular events (8 strokes and 5 transient ischemic episodes) were reported in the anistreplase group, compared with 5 in the placebo group (5 and 0, respectively). The mean systolic and diastolic pressures were significantly lower (by 5-10 mmHg) in patients in the anistreplase group during the first 24 hours after dosing. There were no significant differences in temperature and pulse rate between the two groups. The incidence of chest pain during the first 4- to 24-h period was lower in the anistreplase-treated patients than in the placebo group. The frequency of in-hospital reinfarction was higher in anistreplase-treated patients compared with patients given placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗