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PubMed1997

Comparison of fluoxetine, bupropion, and placebo in the treatment of premenstrual dysphoric disorder.

Serotonergic antidepressants have been shown to be effective treatments for premenstrual dysphoric disorder (PMDD). The efficacy of nonserotonergic antidepressants is less well studied. This study was a two-center, parallel design, placebo-controlled, randomized trial of fluoxetine, bupropion, and placebo in women with PMDD. Thirty-four women with PMDD completed 1 month of single-blind placebo and 2 months of fluoxetine 20 mg/day (N = 10), bupropion 100 mg three times daily (N = 12), or placebo (N = 12). Clinical Global Impressions (CGI) Scale, an expanded form of the Hamilton Rating Scale for Depression (HAM-D), and Global Assessment Scale (GAS) ratings were obtained premenstrually in each of the three treatment cycles. The three treatment groups differed significantly in efficacy by CGI ratings. Fluoxetine was superior to both bupropion and placebo. Comparison of posttreatment to pretreatment HAM and GAS scores demonstrated significant superior efficacy of fluoxetine compared with placebo. Posttreatment HAM and GAS scores for bupropion were intermediate between but not significantly different from fluoxetine or placebo. In summary, fluoxetine was significantly superior to bupropion and placebo as an effective treatment for PMDD. Although some improvement with bupropion was noted, and both medications were well tolerated, patient satisfaction was far greater with fluoxetine.

Adolescent↗
PubMed2004

Parecoxib sodium demonstrates gastrointestinal safety comparable to placebo in healthy subjects.

BACKGROUND: The gastrointestinal safety of the novel injectable cyclooxygenase-2 selective inhibitor, parecoxib sodium, was compared with the nonselective nonsteroidal anti-inflammatory drug, ketorolac, and placebo in healthy subjects. STUDY: In a multicenter, randomized, double-blind, placebo-controlled design, 123 adults with endoscopically-confirmed normal upper gastrointestinal mucosae received parecoxib sodium 40 mg twice daily (7 days); placebo (2 days) followed by ketorolac 30 mg 4 times daily (5 days); or placebo (7 days) (each group n = 41). Posttreatment endoscopy scores were analyzed at 3 levels of severity: ulcers (scores of 7), > or =11 erosions/ulcers (scores of 5-7), and any erosions/ulcers (scores of 3-7). RESULTS: No subjects treated with parecoxib sodium or placebo developed gastroduodenal ulcers or > or =11 erosions/ulcers. Parecoxib sodium was comparable to placebo with respect to the combined incidence of erosions/ulcers (12% vs. 7%, P = 0.419). In contrast, in the ketorolac group, 11 (28%) subjects developed ulcers, 19 (48%) subjects developed > or =11 gastroduodenal erosions/ulcers, and the rate of combined ulcers/erosions was 85% (P < 0.001 vs. placebo and parecoxib sodium). CONCLUSIONS: Parecoxib sodium 40 mg twice daily for 7 days has a gastrointestinal safety profile superior to ketorolac 30 mg 4 times daily for 5 days, and comparable to placebo.

Adult↗
PubMed1993

A 24-week study of 20 mg citalopram, 40 mg citalopram, and placebo in the prevention of relapse of major depression.

A total of 147 patients who had responded in a placebo-controlled study to 6 weeks treatment of an episode of DSM-III-R major depression with either 20 mg or 40 mg citalopram were randomized double-blind to continue on the same dose of citalopram or to receive placebo during a 24-week study of the efficacy of citalopram in the prevention of relapse. The citalopram 20 and 40 mg groups showed a significant advantage compared with placebo both in relapses (p < 0.05) and in the survival analysis of time to relapse (p = 0.01 and p = 0.02, respectively). Both 20 and 40 mg citalopram appeared similarly safe and well tolerated with little difference in side effects from placebo. The results demonstrate that citalopram, at a dose of both 20 and 40 mg is effective and well tolerated in continuation treatment to consolidate response. The relapse rate in patients who had responded to placebo during the 6-week acute treatment study, who were continued double-blind with placebo but not included in the efficacy analysis, was similar to the rate in the formal placebo control group, suggesting that patients who respond to placebo in a short treatment course may nonetheless require long-term active treatment to prevent relapse.

Citalopram↗
PubMed1987

Placebo-controlled study of lisinopril in congestive heart failure: a multicentre study.

A double-blind randomised, parallel, placebo-controlled study was performed in patients with congestive heart failure, at 13 centres in 10 countries, to assess the efficacy and safety of lisinopril, a new angiotensin-converting enzyme inhibitor. After a 2-week run-in period, 130 patients receiving digoxin and/or diuretics were randomised to 12 weeks of treatment with lisinopril 5 mg daily (87 patients) or with placebo (43 patients), with an option to increase lisinopril dosage to 10 or 20 mg. Patients treated with lisinopril improved significantly more than placebo-treated patients (p less than 0.05) for all clinical parameters except oedema and paroxysmal nocturnal dyspnoea. Left ventricular ejection fraction rose by 8% in lisinopril patients compared to 2% in the placebo group, while the cardiothoracic ratio and echocardiographic end systolic diameter fell in the lisinopril group (p less than 0.01) but not in the placebo group. Exercise duration was greater in the lisinopril group at all timepoints, and the increase in exercise duration at 12 weeks was greater by more than 2 min in the lisinopril group as compared to the placebo group (p less than 0.01). Changes in clinical and noninvasive parameters such as the New York Heart Association status, were well correlated with changes in exercise duration. Four patients in the lisinopril group and three in the placebo group died in this study, and there were 31 adverse clinical experiences in the 87 lisinopril-treated patients compared to 13 in the 43 placebo-treated patients. We conclude that lisinopril in doses of 2.5-20 mg/day is well tolerated and effective in patients with heart failure who are receiving digitalis and diuretics.

Adolescent↗
PubMed1996

Randomized, placebo-controlled, double blinded trial of dexamethasone in African children with sepsis.

OBJECTIVE: To determine the effect of moderate dose dexamethasone administered before antibiotics on the outcome of African children with sepsis. METHODS: The design was a randomized, double blinded, placebo-controlled trial of dexamethasone (0.2 mg/kg) vs. placebo given intravenously before antibiotic therapy. Patients were recruited from the patient populations at two missionary hospitals. Primary outcome variables were determined before analysis of data. RESULTS: Seventy-two children with sepsis were enrolled in the study. Treatment with dexamethasone was not associated with improved outcome for any of six outcome variables: survival to discharge (83%, dexamethasone group; 89%, placebo group); hemodynamic stability at 48 h (33%, dexamethasone group; 49%, placebo group); median length of hospital stay (11 days, dexamethasone group; 11 days, placebo group); normal at discharge (90%, dexamethasone group; 75%, placebo group); normal at follow-up (90%, dexamethasone group; 72%, placebo group); and afebrile at 48 to 72 h (61%, dexamethasone group; 44%, placebo group). CONCLUSIONS: These data indicate that a moderate dose of dexamethasone given before antibiotic therapy did not improve outcome in the pediatric patients with sepsis whom we studied.

Adolescent↗
PubMedDate not supplied

Efficacy and safety of fluoxetine in the treatment of patients with major depression after first myocardial infarction: findings from a double-blind, placebo-controlled trial.

OBJECTIVE: Depression and hostility are significant risk factors for mortality and morbidity after myocardial infarction (MI). Much research is still needed to identify effective ways to reduce emotional distress in patients with cardiovascular disease. This double-blind, placebo-controlled study investigated the efficacy and safety of the antidepressant fluoxetine in patients with depression after their first MI. METHODS: Fifty-four patients with major depression after MI were randomly assigned to receive a flexible-dose regimen of fluoxetine or placebo for the first 9 weeks of a double-blind, placebo-controlled trial. Patients without serious adverse effects who wished to continue participating in the study were given fluoxetine or placebo for an additional 16 weeks. To evaluate the efficacy of fluoxetine, the 17-item Hamilton Depression Rating Scale (HAMD-17) and the Hostility Scale of the 90-item Symptom Check List (SCL-90) were used as primary measures of outcome. To evaluate the safety of fluoxetine, cardiac function was measured before and after treatment with echocardiography and electrocardiography. RESULTS: The a priori difference in antidepressive efficacy (4-point difference in HAMD-17 scores between the fluoxetine and placebo groups) was not met. However, the response rate among patients receiving fluoxetine was significantly greater than that among patients receiving placebo at week 25 (48 vs. 26%, p = .05). Among patients with mild depression (HAMD-17 score < or =21), HAMD-17 scores were significantly different (p < .05) between the fluoxetine and placebo groups at weeks 9 (by 5.4 points) and 25 (by 5.8 points). Also, hostility scores at week 25 were significantly reduced among patients receiving fluoxetine (p = .02). Analysis of electrocardiographic and echocardiographic parameters revealed no decrease in cardiac function as a result of treatment with fluoxetine. CONCLUSIONS: Although the overall difference between the fluoxetine and placebo groups was not significant, there was a trend favoring fluoxetine in this relatively small sample. The response rate in the group receiving fluoxetine was comparable with that observed in other studies of patients with cardiovascular disease. In addition, fluoxetine seemed to be particularly effective in patients with mild depression and was associated with a statistically significant reduction in hostility. The results of this study suggest that fluoxetine can be safely used to treat patients with post-MI depression beginning 3 months after the event.

Adult↗
PubMed1999

Randomized, placebo-controlled, double-blind, multicenter trial of efficacy and safety of granulocyte colony-stimulating factor in liver transplant recipients.

BACKGROUND: Infection and rejection are two common complications after liver transplants. In a preliminary study, administration of granulocyte colony-stimulating factor (G-CSF) to liver transplant recipients was associated with a decrease in sepsis episodes, sepsis-related deaths, and rejection compared with a historical control group of patients. The purpose of this study was to evaluate further the efficacy of G-CSF in liver transplant patients in a randomized, placebo-controlled, double-blind, multicenter trial. METHODS: Adult patients with a United Network Organ Sharing classification of 1 or 2 were randomized to receive a placebo, 100 microg/day of G-CSF or 300 microg/day of G-CSF. The study drug was started preoperatively and then continued after the transplant for a maximum of 21 days. Patients were evaluated for microbiologically-documented infection, biopsy-proven rejection, number of treatments for rejection, length of stay in the intensive care unit and hospital, graft survival, death, and adverse events. RESULTS: During the first 30 days after the transplant, the median peak white blood cell count was 16.5x10(9)/L, 34.6x10(9)L, and 54.8x10(9)/L for the placebo, low-dose G-CSF, and high-dose G-CSF patients, respectively. The incidence of infection was 30% in G-CSF patients (34 of 114 patients) and 34% in placebo patients (20 of 58 patients). Except for more nosocomial pneumonias in the G-CSF patients (7 in 114 patients vs. 0 in 58 patients, P=0.056), the types of infections and causative organisms were also similar in both treatment groups. Although the number of treatments for clinically suspected or proven rejection was similar in the G-CSF and placebo patients, biopsy-proven rejection occurred more often in G-CSF patients (34 of 114 patients or 30%) than placebo patients (11 of 58 patients or 19%) (P=0.093). There were no cases of graft loss caused by rejection. G-CSF had no effect on length of stay in the intensive-care unit or hospital. There were 22 G-CSF patients (18%) and 10 placebo patients (15%) who died within 120 days after the transplant. No serious adverse events were attributed to G-CSF. CONCLUSION: Despite producing substantial increases in the white blood cell count after the transplant, G-CSF had no beneficial effects on infection, rejection, or survival in this study. Biopsy-proven rejection and nosocomial pneumonias were more common in patients treated with G-CSF compared with those taking the placebo. No serious adverse events were attributed to G-CSF.

Adolescent↗
PubMed2006

Efficacy of recombinant human erythropoietin in critically ill patients admitted to a long-term acute care facility: a randomized, double-blind, placebo-controlled trial.

CONTEXT: Anemia is common in the critically ill and results in a large number of red blood cell transfusions. Recent data have shown that red blood cell transfusions in critically ill patients can be decreased with recombinant human erythropoietin (rHuEPO) therapy during their intensive care unit stay. OBJECTIVE: To assess the efficacy of rHuEPO therapy in decreasing the occurrence of red blood cell transfusions in patients admitted to a long-term acute care facility (LTAC). DESIGN: A prospective, randomized, double-blind, placebo-controlled, multiple-center trial. SETTING: Two long-term acute care facilities. PATIENTS: A total of 86 patients who met eligibility criteria were enrolled in the study with 42 randomized to rHuEPO and 44 to placebo. INTERVENTIONS: Study drug (rHuEPO 40,000 units) or a placebo was administered by subcutaneous injection before day 7 of long-term acute care facility admission and continued weekly for up to 12 doses. MAIN OUTCOME MEASURES: The primary efficacy end point was cumulative red blood cell units transfused. Secondary efficacy end points were the percent of patients receiving any red blood cell transfusion; the percent of patients alive and transfusion independent; cumulative mortality; and change in hematologic variables from baseline. Logistic regression was used to adjust the odds ratio for red blood cell transfusion. All end points were assessed at both study day 42 and study day 84. RESULTS: The baseline hemoglobin level was higher in the rHuEPO group (9.9 +/- 1.15 g/dL vs. 9.3 +/- 1.41 g/dL, p = .02) as was the pretransfusion hemoglobin level (8.0 +/- 0.5 g/dL vs. 7.5 +/- 0.8 g/dL, p = .04). At day 84, patients receiving rHuEPO received fewer red blood cell transfusions (median units per patient 0 vs. 2, p = .05), and the ratio of red blood cell transfusion rates per day alive was 0.61 with 95% confidence interval of 0.2, 1.01, indicating a 39% relative reduction in transfusion burden for the rHuEPO group compared with placebo. There was also a trend at day 84 toward a reduction in the total units of red blood cells transfused in the rHuEPO group (113 units of placebo vs. 73 units of rHuEPO). Patients receiving rHuEPO were also less likely to be transfused (64% placebo vs. 41% rHuEPO, p = .05; adjusted odds ratio 0.47, 95% confidence interval 0.19, 1.16). Most of the transfusion benefit of rHuEPO occurred by study day 42. Increase in hemoglobin from baseline to final was greater in the rHuEPO group (1.0 +/- 2 g/dL vs. 0.4 +/- 1.7 g/dL, p < .001). Mortality rate (19% rHuEPO, 29.5% placebo, p = .17; relative risk, 0.55, 95% confidence interval 0.21-1.43) and serious adverse clinical events (38 % rHuEPO, 32% placebo, p = .65) were not significantly different between the two groups. CONCLUSIONS: In patients admitted to a long-term acute care facility, administration of weekly rHuEPO results in a significant reduction in exposure to allogeneic red blood cell transfusion during the initial 42 days of rHuEPO therapy, with little additional benefit achieved with therapy to 84 days. Despite receiving fewer red blood cell transfusions, patients treated with rHuEPO achieve a higher hemoglobin level.

Aged↗
PubMedDate not supplied

Tibolone for the treatment of moderate to severe vasomotor symptoms and genital atrophy in postmenopausal women: a multicenter, randomized, double-blind, placebo-controlled study.

OBJECTIVE: To demonstrate the safety and efficacy of tibolone (1.25 and 2.5 mg) in the treatment of moderate to severe vasomotor symptoms and symptoms associated with vaginal atrophy. DESIGN: A placebo-controlled, double-blind, randomized, multicenter study was conducted on 396 healthy postmenopausal women experiencing a minimum of 7 moderate to severe hot flashes per day (60 per week). Participants were randomized to receive tibolone 1.25 or 2.5 mg or placebo once daily for 12 weeks. Assessments were done at weeks 4, 8, and 12. The severity and frequency of hot flashes were recorded in patient diaries on a daily basis. RESULTS: Tibolone 2.5 mg significantly (P < 0.001) reduced the average number of hot flashes compared with placebo at week 4 (-7.82 vs -5.27), week 8 (-9.71 vs -5.86), and week 12 (-10.14 vs -5.85). The difference between tibolone 1.25 mg and placebo was significant (P < 0.001) at week 8 (-7.96) and week 12 (-8.32). Findings for the average daily severity of hot flashes were similar, with significantly greater reductions at week 4 (P < 0.05) and weeks 8 and 12 (P < 0.001) for tibolone 2.5 mg versus placebo and at weeks 8 and 12 for tibolone 1.25 mg versus placebo (P < 0.001). A menopausal atrophic symptom questionnaire revealed that tibolone 2.5 mg significantly (P < 0.05) reduced nocturia compared with placebo at weeks 4, 8, and 12 and urinary urgency at week 4. Compared with placebo, both doses of tibolone also significantly (P < 0.001) increased the vaginal maturation value from baseline. The overall incidence of adverse events was similar in all treatment groups. CONCLUSIONS: Tibolone is effective and well tolerated for the treatment of moderate to severe vasomotor symptoms and the effects of vaginal atrophy associated with menopause.

Atrophy↗
PubMed2006

A randomized, double-blind, placebo-controlled study of citalopram in adolescents with major depressive disorder.

In a European, multicenter, double-blind study, 244 adolescents, 13 to 18 years old, with major depression were randomized to treatment with citalopram (n = 124) or placebo (n = 120). One third of the patients in both groups withdrew from the study. No significant differences in improvement of scores from baseline to week 12 between citalopram and placebo were found. The response rate was 59% to 61% in both groups according to the Schedule for Affective Disorders and Schizophrenia for school-aged children-Present episode version (Kiddie-SADS-P) (depression and anhedonia scores < or =2) and Montgomery Asberg Depression Rating Scale (MADRS) (> or =50% reduction). Remission (MADRS score < or =12) was achieved by 51% of patients with citalopram and 53% with placebo. A post hoc analysis revealed that more than two thirds of all patients received psychotherapy during this study. For those patients not receiving psychotherapy, there was a higher percentage of Kiddie-SADS-P responders with citalopram (41%) versus placebo (25%) and a significantly higher percentage of MADRS responders and remitters with citalopram (52% and 45%, respectively) versus placebo (22% and 19%, respectively). Mild to moderate treatment-emergent adverse events were reported in 75% citalopram and 71% of placebo patients, most commonly headache, nausea, and insomnia. Serious adverse events occurred in 14% to 15% in both groups. Suicide attempts, including suicidal thoughts and tendencies, were reported by 5 patients in the placebo group and by 14 patients in the citalopram group (not significant) with no pattern with respect to duration of treatment, time of onset, or dosage. In contrast, the suicidal ideation (Kiddie-SADS-P) single item showed worsening more frequently in the placebo (18%) than in the citalopram group (8%).

Adolescent↗
PubMed2003

A randomized, placebo controlled, multicenter study to evaluate the safety and efficacy of rofecoxib in the treatment of chronic nonbacterial prostatitis.

PURPOSE: We determine the effects of treatment with rofecoxib and placebo in patients with chronic prostatitis. MATERIALS AND METHODS: Patients diagnosed with chronic nonbacterial prostatitis were randomized to 6 weeks of 25 or 50 mg., rofecoxib or placebo in a double-blind multicenter study with a 1-week run in of placebo. End points included the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) (average pain score item 4 primary end point), and patient global assessment questions of pain, disease activity and response to therapy. RESULTS: A total of 161 patients were randomized in the study. The NIH-CPSI total, domain and pain scores significantly decreased from baseline in all groups and, although the mean scores numerically favored the rofecoxib groups, the difference was not significantly different among groups. There was a trend for the percentage of patients with a 25% (or 6 point) improvement in total score being superior on rofecoxib versus placebo with the difference being significantly different (p <0.05) for the 50 mg. rofecoxib group. Patient global assessment of pain, response to therapy and disease activity also favored rofecoxib over placebo (p <0.05, p = 0.07, p = 0.06, respectively). Of the patients 79% on 50 mg. rofecoxib versus 59% on placebo reported no or mild pain, and 56% of patients on 50 mg. rofecoxib versus 27% on placebo experienced significant improvement in quality of life (p <0.005). Rofecoxib was generally well tolerated. CONCLUSIONS: To our knowledge this study is the first to evaluate rofecoxib versus placebo in patients with prostatitis and the first large multicenter treatment study to use the NIH-CPSI. Subjective assessment with patient global questions may be more sensitive to change than the NIH-CPSI and, therefore, may be a better tool to use in future therapeutic trials. Although 6 weeks of rofecoxib treatment appear to benefit many men diagnosed with chronic prostatitis/chronic pelvic pain syndrome further studies are needed.

Adult↗
PubMed2005

Double-blind placebo controlled study of alpha-adrenergic receptor antagonists (doxazosin) for treatment of voiding dysfunction in the pediatric population.

PURPOSE: We sought to determine whether the alpha-adrenergic antagonist doxazosin could be used as primary therapy in children with voiding dysfunction. MATERIALS AND METHODS: Children were assigned to maintain a voiding diary and then randomly divided into a double-blind placebo controlled protocol (0.5 mg doxazosin or placebo). Duplicate uroflow studies with post-void residual evaluations and assessment of dysfunctional voiding scores were performed on initiation and completion of the study. At the conclusion parents were asked to rank the perceived improvement of the urinary incontinence (ie parental subjective perception of improvement). RESULTS: No significant differences between doxazosin (18) and placebo (20) treated patients were found in the number of incontinent days per week, severity of incontinent episodes or alterations in uroflow patterns. Although not significant, 2 findings suggested a beneficial effect of doxazosin over placebo. Specifically, doxazosin decreased the number of incontinent episodes weekly from a median of 18 to 4, while the number of incontinent episodes weekly in the placebo group remained essentially unchanged, decreasing from 15 to 14 (p = 0.13). Doxazosin also improved the dysfunctional voiding scores over placebo, for an improvement of -3 vs 0 points. Further substantiating a doxazosin effect over placebo was the subjective perception of the parents that doxazosin significantly improved urinary continence (p <0.02). CONCLUSIONS: Compared to placebo, doxazosin did not demonstrate a significant objective benefit, but produced a significant subjective benefit in the treatment of urinary incontinence secondary to voiding dysfunction.

Adolescent↗
PubMed2006

Outcomes of placebo therapy in inflammatory bowel disease.

Placebo is important in assessing drug response, particularly in diseases characterized by spontaneous periods of acute exacerbation and quiescence. Randomized, placebo-controlled trials are the most objective means of evaluating drug efficacy, although the conduct of such clinical trials may not always be practical or ethical in all disease states. In inflammatory bowel disease (IBD), most patients experience intermittent episodes of active disease alternating with variable periods of remission. Thus, development of new medical therapies for IBD requires proof of superiority to placebo or alternative therapies. In this regard, knowledge of the outcomes of patients receiving placebo therapy and their influencing factors is important for proper study design and meaningful results. Such knowledge also is essential for interpreting results of open-label studies often necessary before randomized controlled trials can be conducted. In addition, the disease course of placebo-treated patients in clinical trials of IBD serves as an approximation of the natural history of these patients. The knowledge of placebo response in these patients provides clinicians with an important piece of information in prognosticating and making management decisions. This review presents our current knowledge of placebo therapy in IBD. Specifically, the existing literature on the outcomes and predictors of outcomes in patients receiving placebo therapy in clinical trials of IBD is reviewed.

Anti-Inflammatory Agents↗
PubMed2004

Low molecular weight heparin (tinzaparin) vs. placebo in the treatment of mild to moderately active ulcerative colitis.

BACKGROUND: Heparin has anti-inflammatory and immunomodulatory activity which may be of therapeutic benefit in the treatment of ulcerative colitis. AIM: To test whether low molecular weight heparin, given subcutaneously, would provide a significant therapeutic response compared with placebo in the treatment of mild to moderate ulcerative colitis. STUDY DESIGN: A prospective, double-blind, randomized, placebo-controlled, multi-centre trial comparing tinzaparin 175 anti-Xa IU/kg/day (innohep, LEO Pharma) subcutaneously for 14 days followed by tinzaparin 4500 anti-Xa IU/day subcutaneously for 28 days with placebo, administered subcutaneously once daily for up to 42 days. The primary outcome measure was the mean change in colitis activity from baseline to the end of study treatment assessed by the sum of scores of stool frequency, rectal bleeding, sigmoidoscopic appearance and histology. Secondary outcome measures included changes in individual activity indices and laboratory parameters. Patients were assessed at weekly intervals for 6 weeks and within 1 week of completing treatment. RESULTS: One hundred patients with active ulcerative colitis (up to six bloody stools per day, no fever, no tachycardia or systemic disturbances) were randomized. Forty-eight received tinzaparin and 52 received placebo. The difference in the mean percentage change in colitis activity from baseline to end of treatment (tinzaparin-placebo) was not statistically significant (P = 0.84). There was no difference between tinzaparin and placebo in any secondary outcome measure. One major bleed (rectal), occurred in a patient receiving placebo. CONCLUSION: This is the largest trial to date of heparin in ulcerative colitis. The results show no benefit of low molecular weight heparin over placebo in mild to moderately active ulcerative colitis.

Adolescent↗
PubMed1997

The effects of combined treatment with beta 1-selective receptor antagonists and lipid-lowering drugs on fat metabolism and measures of fatigue during moderate intensity exercise: a placebo-controlled study in healthy subjects.

AIMS: We examined the effects of different combinations of beta 1-selective adrenoceptor blockers and lipid-lowering drugs, on fat metabolism and fatigue during moderate intensity exercise in 14 healthy young volunteers. METHODS: The study was a randomized crossover design, each subject completing 5, 90 min walks at 50% of predetermined maximal oxygen uptake (VO2 max), one following each 3 day treatment period with either: atenolol 100 mg and bezafibrate 400 mg, atenolol 100 mg and fluvastatin 40 mg, metoprolol CR 100 mg and bezafibrate 400 mg, metoprolol CR 100 mg and fluvastatin 40 mg, or placebo. RESULTS: Plasma free fatty acid (FFA) concentration during exercise was significantly reduced on all treatments, in comparison with placebo, P = 0.0001. Following 90 min of exercise FFA levels were as follows: placebo 573 mumol l-1 (105-1041), metoprolol CR + fluvastatin 277 mumol l-1 (0-647), metoprolol CR + bezafibrate 182 mumol l-1 (0-396), atenolol + fluvastatin 211 mumol l-1 (0-511), and atenolol + bezafibrate 123 mumol l-1 (0-352). Total fat oxidation during exercise was also reduced on all treatments in comparison with placebo: 38.1% (2-74), compared with 29.1% (0-61) on metoprolol CR + fluvastatin, P = 0.02, 26.2% (2-51) on metoprolol CR + bezafibrate, P = 0.002, 25.5% (3-48) on atenolol + fluvastatin, P = 0.009, and 22.8% (0-47) on atenolol + bezafibrate treatment, P = 0.0002. Plasma ammonia concentration was elevated on all treatments during exercise in comparison with placebo. After 90 min of exercise, plasma ammonia levels were as follows: placebo 37 mumol l-1 (0-84), metoprolol CR + fluvastatin 56 mumol l-1 (2-110), metoprolol CR + bezafibrate 79 mumol l-1 (0-167), atenolol + fluvastatin 90 mumol l-1 (10-170), and atenolol + bezafibrate 100 mumol l-1 26-174). In comparison with placebo, metoprolol CR + fluvastatin had the least adverse impact on measures of perceived exertion and the 'feeling scale' during exercise. Metoprolol CR + bezafibrate, atenolol + fluvastatin, and atenolol + bezafibrate treatments had greater adverse effects, particularly on perceived 'cardiorespiratory effort' and 'feeling scale' scores. CONCLUSIONS: In healthy volunteers, combinations of beta 1-selective blockers and lipid-lowering drugs were associated with significant reductions in fat metabolism, increased plasma ammonia levels, and raised the perception of effort during exercise, in comparison with placebo. Metoprolol CR + fluvastatin had the least effect, combinations metoprolol CR + bezafibrate and atenolol + fluvastatin had intermediate effects, and atenolol + bezafibrate had the most adverse effect.

Adrenergic beta-Antagonists↗
PubMed2006

CLinical experience acquired with the efalizumab (Raptiva) (CLEAR) trial in patients with moderate-to-severe plaque psoriasis: results from a phase III international randomized, placebo-controlled trial.

BACKGROUND: Efalizumab (anti-CD11a), a humanized monoclonal antibody, blocks multiple T-cell-dependent functions implicated in the pathogenesis of psoriasis, including T-cell activation, migration to the skin, reactivation in psoriatic skin and interactions with keratinocytes. OBJECTIVES: This multinational, randomized, double-blind, placebo-controlled, parallel-group trial was designed to evaluate the safety and efficacy of subcutaneous efalizumab 1.0 mg kg-1 once weekly for 12 weeks compared with placebo in a population that included high-need patients, defined as those for whom at least two systemic therapies were unsuitable because of lack of efficacy, intolerance or contraindication. PATIENTS/METHODS: Patients with moderate-to-severe plaque psoriasis [involvement of >or=10% of total body surface area and Psoriasis Area and Severity Index (PASI)>or=12.0 at screening] were randomized in a 2:1 ratio to receive efalizumab or placebo. The primary efficacy endpoint was the proportion of patients achieving >or=75% PASI improvement (PASI-75 response) at week 12 in the intention-to-treat population; secondary endpoints included changes in PASI, static Physician's Global Assessment, Physician's Global Assessment of change from baseline and percentage of body surface area affected. Results We enrolled 793 patients (529 received efalizumab and 264 placebo), including 526 high-need patients (342 received efalizumab and 184 placebo). Week 12 PASI-75 rates were 29.5% for efalizumab compared with 2.7% for placebo among high-need patients (P<0.0001) and 31.4% for efalizumab compared with 4.2% for placebo in the full study population (P<0.0001). RESULTS: for all secondary efficacy endpoints showed superiority of efalizumab over placebo in both the high-need and the full populations. Efalizumab demonstrated a favourable safety profile, without evidence of systemic toxicity, in both the high-need group and the overall study population. CONCLUSIONS: The efficacy and safety of efalizumab therapy were comparable between high-need patients and the more general moderate-to-severe psoriasis patient population. In view of its demonstrated efficacy and safety profile, efalizumab represents a valuable option for the treatment of adult patients with moderate-to-severe plaque psoriasis, including high-need patients.

Adult↗
PubMed2004

Effect of homocysteine-lowering treatment with folic acid plus vitamin B on cerebrovascular atherosclerosis and white matter abnormalities as determined by MRA and MRI: a placebo-controlled, randomized trial.

BACKGROUND: A high plasma homocysteine concentration is an independent risk factor for large and possibly small vessel disease. We investigated the effects of homocysteine-lowering treatment with folic acid plus vitamin B(6) on markers of cerebrovascular atherosclerosis and cerebral microangiopathy. MATERIALS AND METHODS: Using 158 healthy siblings (mean age 46.0 +/- 7.6 years) of patients with premature atherosclerotic disease, we performed a randomized, placebo-controlled trial using 5 mg of folic acid plus 250 mg of vitamin B(6) daily (n = 78) or placebo medication (n = 80). Participants were followed for 2 years with magnetic resonance angiography (MRA) (carotid stenosis; carotid and/or vertebral elongation) and magnetic resonance imaging (MRI) (white matter abnormalities; cerebral atrophy). RESULTS: Seventeen (10.8%) subjects refused MRA/MRI owing to claustrophobia and were excluded. From the remaining 141 participants, 68 received vitamin and 73 received placebo medication [42 (61.8%) and 48 (65.8%) had postmethionine hyperhomocysteinaemia, respectively]. Twenty-four participants (15.2%; 10 in the treatment and 14 in the placebo group) did not complete both years of the trial. Vitamin treatment was associated with an increase in plasma folate (13-fold vs. placebo; P < 0.001) and vitamin B(6) (8.8-fold; P < 0.001). Fasting and postmethionine total homocysteine concentrations decreased 38.7% (95% CI, 27.4-50.0) and 29.1% (95% CI, 19.2-39.0) vs. placebo (all P < 0.001). During follow up six individuals in the vitamin-treated and 11 in the placebo-treated group deteriorated in their outcome measurements. Vitamin treatment, as compared with placebo, was associated with nonsignificantly improved outcomes on both MRA and MRI outcome measurements (odds ratio 0.48; 95% CI 0.17-1.41; P = 0.18 and 0.48; CI 0.14-1.60; P = 0.23, respectively). CONCLUSIONS: These results could indicate a possible favourable effect of homocysteine-lowering treatment on cerebrovascular atherosclerosis and cerebral microangiopathy among healthy siblings of patients with premature atherosclerotic disease, but larger trials are required to establish this with certainty.

Adult↗
PubMed2005

Double-blind and placebo-controlled study to assess efficacy and safety of a modified allergen extract of Dermatophagoides pteronyssinus in allergic asthma.

BACKGROUND: A randomized double-blind, placebo-controlled study was conducted in patients allergic asthma sensitized to Dermatophagoides pteronyssinus. OBJECTIVE: To evaluate the efficacy and safety after 1-year of immunotherapy with a modified D. pteronyssinus extract compared with placebo. MATERIAL AND METHODS: Fifty-five patients were randomly allocated to receive the active treatment (n = 29), or placebo (n = 26). The main outcome was the specific bronchial provocation test (BPT). Other parameters analysed were dose-response skin prick test (SPT), symptom and medication scores and asthma quality of life (AQLQ). RESULTS: At the end of the study, the active group showed a significant increase in the PD(20)FEV(1) compared with placebo (P = 0.0029). Nineteen patients of the active vs 10 of the placebo group needed more than twice the initial amount of allergen extract to have a positive BPT (P = 0.0293); seven patients in the placebo vs one in the active group needed less than half (P = 0.0137). In SPT, a significant improvement (P = 0.0049) was found in the active group. This group also had a median reduction of 91.5% in symptom scores, whereas the placebo group increased by 86%. Medication scores decreased in both groups (56% in the active and 11.4% in the placebo). In AQLQ, the differences between both groups were significant (P = 0.0234) at the end of the study. CONCLUSION: After 1 year of treatment, the modified extract of D. pteronyssinus demonstrated to be safe and efficacious to treat patients with asthma and allergic rhinoconjunctivitis sensitized to this mite.

Adolescent↗