Showing papers on "Placebo-controlled study published in 2004"
TL;DR: Atorvastatin 10 mg daily is safe and efficacious in reducing the risk of first cardiovascular disease events, including stroke, in patients with type 2 diabetes without high LDL-cholesterol.
3,578 citations
01 Jan 2004
TL;DR: The purpose of the present investigation was to evaluate the safety and effectiveness of the antiviral drug amantadine for the treatment of hepatitis C in those who had either previously failed interferon therapy or were not candidates for interferons.
Abstract: Although treatment of hepatitis C has improved,up to 50% do not respond to standard therapy with interferonregimes or cannot tolerate the treatment due to side effects.The purpose of the present investigation was to evaluate thesafety and effectiveness of the antiviral drug amantadine forthe treatment of hepatitis C in those who had either previouslyfailed interferon therapy or were not candidates for interferon.
2,865 citations
TL;DR: The short‐term efficacy of opioids was good in both neuropathic and musculoskeletal pain conditions, however, only a minority of patients in these studies went on to long‐term management with opioids, and conclusions concerning problems such as tolerance and addiction are not allowed.
Abstract: Opioids are used increasingly for chronic non-cancer pain. Controversy exists about their effectiveness and safety with long-term use. We analysed available randomised, placebo-controlled trials of WHO step 3 opioids for efficacy and safety in chronic non-cancer pain. The Oxford Pain Relief Database (1950-1994) and Medline, EMBASE and the Cochrane Library were searched until September 2003. Inclusion criteria were randomised comparisons of WHO step 3 opioids with placebo in chronic non-cancer pain. Double-blind studies reporting on pain intensity outcomes using validated pain scales were included. Fifteen randomised placebo-controlled trials were included. Four investigations with 120 patients studied intravenous opioid testing. Eleven studies (1025 patients) compared oral opioids with placebo for four days to eight weeks. Six of the 15 included trials had an open label follow-up of 6-24 months. The mean decrease in pain intensity in most studies was at least 30% with opioids and was comparable in neuropathic and musculoskeletal pain. About 80% of patients experienced at least one adverse event, with constipation (41%), nausea (32%) and somnolence (29%) being most common. Only 44% of 388 patients on open label treatments were still on opioids after therapy for between 7 and 24 months. The short-term efficacy of opioids was good in both neuropathic and musculoskeletal pain conditions. However, only a minority of patients in these studies went on to long-term management with opioids. The small number of selected patients and the short follow-ups do not allow conclusions concerning problems such as tolerance and addiction.
1,156 citations
TL;DR: There is no reduction in mortality with methylprednisolone in the 2 weeks after head injury, and the risk of death from all causes within 2 weeks was higher in the group allocated corticosteroids.
958 citations
TL;DR: Dalteparin 5000 IU once daily halved the rate of venous thromboembolism with a low risk of bleeding and was maintained at 90 days.
Abstract: Background— Considerable variability exists in the use of pharmacological thromboprophylaxis among acutely ill medical patients, partly because clinically relevant end points have not been fully assessed in this population. We undertook an international, multicenter, randomized, double-blind, placebo-controlled trial using clinically important outcomes to assess the efficacy and safety of dalteparin in the prevention of venous thromboembolism in such patients. Methods and Results— Patients (n=3706) were randomly assigned to receive either subcutaneous dalteparin 5000 IU daily or placebo for 14 days and were followed up for 90 days. The primary end point was venous thromboembolism, defined as the combination of symptomatic deep vein thrombosis, symptomatic pulmonary embolism, and asymptomatic proximal deep vein thrombosis detected by compression ultrasound at day 21 and sudden death by day 21. The incidence of venous thromboembolism was reduced from 4.96% (73 of 1473 patients) in the placebo group to 2.77%...
922 citations
TL;DR: After 7.5 years, low-dose antioxidant supplementation lowered total cancer incidence and all-cause mortality in men but not in women, suggesting that supplementation may be effective in men only because of their lower baseline status of certain antioxidants, especially of beta carotene.
Abstract: Background It has been suggested that a low dietary intake of antioxidant vitamins and minerals increases the incidence rate of cardiovascular disease and cancer. To date, however, the published results of randomized, placebo-controlled trials of supplements containing antioxidant nutrients have not provided clear evidence of a beneficial effect. We tested the efficacy of nutritional doses of supplementation with a combination of antioxidant vitamins and minerals in reducing the incidence of cancer and ischemic cardiovascular disease in the general population. Methods The Supplementation en Vitamines et Mineraux Antioxydants (SU.VI.MAX) study is a randomized, double-blind, placebo-controlled primary prevention trial. A total of 13 017 French adults (7876 women aged 35-60 years and 5141 men aged 45-60 years) were included. All participants took a single daily capsule of a combination of 120 mg of ascorbic acid, 30 mg of vitamin E, 6 mg of beta carotene, 100 μg of selenium, and 20 mg of zinc, or a placebo. Median follow-up time was 7.5 years. Results No major differences were detected between the groups in total cancer incidence (267 [4.1%] for the study group vs 295 [4.5%] for the placebo group), ischemic cardiovascular disease incidence (134 [2.1%] vs 137[2.1%]), or all-cause mortality (76 [1.2%] vs 98 [1.5%]). However, a significant interaction between sex and group effects on cancer incidence was found ( P = .004). Sex-stratified analysis showed a protective effect of antioxidants in men (relative risk, 0.69 [95% confidence interval {CI}, 0.53-0.91]) but not in women (relative risk, 1.04 [95% CI, 0.85-1.29]). A similar trend was observed for all-cause mortality (relative risk, 0.63 [95% CI, 0.42-0.93] in men vs 1.03 [95% CI, 0.64-1.63] in women; P = .11 for interaction). Conclusions After 7.5 years, low-dose antioxidant supplementation lowered total cancer incidence and all-cause mortality in men but not in women. Supplementation may be effective in men only because of their lower baseline status of certain antioxidants, especially of beta carotene.
907 citations
TL;DR: The addition of extended-release niacin to statin therapy slowed the progression of atherosclerosis among individuals with known coronary heart disease and moderately low HDL-C.
Abstract: Background— Niacin reduces coronary heart disease morbidity and mortality when taken either alone or in combination with statins; however, the incremental impact of adding niacin to background statin therapy is unknown. Methods and Results— This was a double-blind randomized placebo-controlled study of once-daily extended-release niacin (1000 mg) added to background statin therapy in 167 patients (mean age 67 years) with known coronary heart disease and low levels of high-density lipoprotein cholesterol (HDL-C; <45 mg/dL). The primary end point was the change in common carotid intima-media thickness (CIMT) after 1 year. Baseline CIMT (0.884±0.234 mm), low-density lipoprotein cholesterol (89±20 mg/dL), and HDL-C (40±7 mg/dL) were comparable in the placebo and niacin groups. Adherence to niacin exceeded 90%, and 149 patients (89.2%) completed the study. HDL-C increased 21% (39 to 47 mg/dL) in the niacin group. After 12 months, mean CIMT increased significantly in the placebo group (0.044±0.100 mm; P<0.001) ...
900 citations
TL;DR: The causes of death in the study were consistent with those expected in patients with septic shock, although there was a higher proportion of cardiovascular deaths and a lower incidence of deaths caused by multiple organ failure in the 546C88 group.
Abstract: Objective: To assess the safety and efficacy of the nitric oxide synthase inhibitor 546C88 in patients with septic shock. The predefined primary efficacy objective was survival at day 28. Design: Multiple-center, randomized, two-stage, double-blind, placebo-controlled, safety and efficacy study. Setting: A total of 124 intensive care units in Europe, North America, South America, South Africa, and Australasia. Patients: A total of 797 patients with septic shock diagnosed for <24 hrs. Interventions: Patients with septic shock were allocated to receive 546C88 or placebo (5% dextrose) for up to 7 days (stage 1) or 14 days (stage 2) in addition to conventional therapy. Study drug was initiated at 0.05 mL·kg 1 ·hr 1 (2.5 mg·kg 1 ·hr 1 546C88) and titrated up to a maximum rate of 0.4 mL·kg 1 ·hr 1 to maintain mean arterial pressure between 70 and 90 mm Hg while attempting to withdraw concurrent vasopressors. Measurements and Main Results: Hemodynamic variables, organ function data, microbiological data, concomitant therapy, and adverse event data were recorded at baseline, throughout treatment, and at follow-up. The primary end point was day-28 survival. The trial was stopped early after review by the independent data safety monitoring board. Day-28 mortality was 59% (259/439) in the 546C88 group and 49% (174/358) in the placebo group (p < .001). The overall incidence of adverse events was similar in both groups, although a higher proportion of the events was considered possibly attributable to study drug in the 546C88 group. Most of the events accounting for the disparity between the groups were associated with the cardiovascular system (e.g., decreased cardiac output, pulmonary hypertension, systemic arterial hypertension, heart failure). The causes of death in the study were consistent with those expected in patients with septic shock, although there was a higher proportion of cardiovascular deaths and a lower incidence of deaths caused by multiple organ failure in the 546C88 group. Conclusions: In this study, the nonselective nitric oxide synthase inhibitor 546C88 increased mortality in patients with septic shock. (Crit Care Med 2004; 32:21‐30)
876 citations
TL;DR: These data show that statins can mediate modest but clinically apparent anti-inflammatory effects with modification of vascular risk factors in the context of high-grade autoimmune inflammation.
789 citations
TL;DR: Treatment with MRA was generally well tolerated and significantly reduced the disease activity of RA, and the adverse events were not dose dependent.
Abstract: Objective
Interleukin-6 (IL-6) is a pleiotropic cytokine that regulates the immune response, inflammation, and hematopoiesis. Overproduction of IL-6 plays pathologic roles in rheumatoid arthritis (RA), and the blockade of IL-6 may be therapeutically effective for the disease. This study was undertaken to evaluate the safety and efficacy of a humanized anti–IL-6 receptor antibody, MRA, in patients with RA.
Methods
In a multicenter, double-blind, placebo-controlled trial, 164 patients with refractory RA were randomized to receive either MRA (4 mg/kg body weight or 8 mg/kg body weight) or placebo. MRA was administered intravenously every 4 weeks for a total of 3 months. The clinical responses were measured using the American College of Rheumatology (ACR) criteria.
Results
Treatment with MRA reduced disease activity in a dose-dependent manner. At 3 months, 78% of patients in the 8-mg group, 57% in the 4-mg group, and 11% in the placebo group achieved at least a 20% improvement in disease activity according to the ACR criteria (an ACR20 response) (P < 0.001 for 8-mg group versus placebo). Forty percent of patients in the 8-mg group and 1.9% in the placebo group achieved an ACR50 response (P < 0.001). The overall incidences of adverse events were 56%, 59%, and 51% in the placebo, 4-mg, and 8-mg groups, respectively, and the adverse events were not dose dependent. A blood cholesterol increase was observed in 44.0% of the patients. Liver function disorders and decreases in white blood cell counts were also observed, but these were mild and transient. There was no increase in antinuclear antibodies or anti-DNA antibodies. Anti-MRA antibodies were detected in 2 patients.
Conclusion
Treatment with MRA was generally well tolerated and significantly reduced the disease activity of RA.
778 citations
TL;DR: The long‐term efficacy and safety of 21 months of treatment with zoledronic acid in a randomized, placebo‐controlled trial are reported.
Abstract: Background The authors previously reported the efficacy of a dose of 4 mg of zoledronic acid in reducing skeletal complications in patients with bone metastases secondary to lung carcinoma and other solid tumors (except carcinomas of the breast and prostate). In the current study, they update these results and report the long-term efficacy and safety of 21 months of treatment with zoledronic acid in a randomized, placebo-controlled trial. Methods A total of 773 patients were randomized to receive zoledronic acid (4 mg or 8 mg) or placebo via a 15-minute infusion every 3 weeks for 21 months. The 8-mg dose later was reduced to 4 mg (8/4-mg group). The primary efficacy endpoint was the percentage of patients at 21 months with >/= 1 skeletal-related event (SRE) (pathologic fracture, spinal cord compression, radiation therapy to bone, or surgery to bone). Secondary analyses (time to first SRE, annual incidence of SREs, and multiple-event analysis) included hypercalcemia of malignancy. Results Fewer patients treated with zoledronic acid developed at least 1 SRE at 21 months compared with patients treated with placebo (39% of those treated at the 4-mg dose [P =0.127] and 36% of those treated at the 8/4-mg dose [P = 0.023], compared with 46% of those treated with placebo). Furthermore, 4 mg of zoledronic acid significantly delayed the median time to first SRE (236 days with 4 mg vs. 155 days with placebo; P = 0.009) and significantly reduced the annual incidence of SREs (1.74 per year with the 4-mg dose vs. 2.71 per year with placebo; P = 0.012). Moreover, the 4-mg dose of zoledronic acid was found to reduce the risk of developing a skeletal event by 31% (hazard ratio of 0.693; P = 0.003). Zoledronic acid was found to be well tolerated with long-term use; the most commonly reported adverse events in all treatment groups included bone pain and the transient, acute-phase reactions of nausea, anemia, and emesis. Conclusions To the authors' knowledge, zoledronic acid is the first bisphosphonate to demonstrate long-term safety and efficacy in this patient population.
TL;DR: In a well-defined population of patients with idiopathic pulmonary fibrosis, interferon gamma-1b did not affect progression-free survival, pulmonary function, or the quality of life.
Abstract: Background Idiopathic pulmonary fibrosis is a progressive, fatal disease with no known efficacious therapy. Methods In a double-blind, multinational trial, we randomly assigned 330 patients with idiopathic pulmonary fibrosis that was unresponsive to corticosteroid therapy to receive subcutaneous interferon gamma-1b or placebo. Results Over a median of 58 weeks, interferon gamma-1b therapy did not significantly affect the primary end point of progression-free survival, defined as the time to disease progression or death, and no significant treatment effect was observed on measures of lung function, gas exchange, or the quality of life. Ten percent of patients in the interferon gamma-1b group died, as compared with 17 percent of patients in the placebo group (P=0.08). Treatment with interferon gamma-1b was associated with more frequent constitutional symptoms. However, the rates of treatment adherence and premature discontinuation of treatment were similar in the two groups. More pneumonias were reported am...
TL;DR: Infliximab treatment resulted in a rapid and significant improvement in the signs and symptoms of psoriasis.
Abstract: Background Tumor necrosis factor–α is a key mediator in the pathogenesis of psoriasis. Infliximab is a monoclonal antibody that specifically binds to tumor necrosis factor-α, blocking its biologic activity. Objective The purpose of this study was to access the efficacy and safety of infliximab induction therapy for patients with severe plaque psoriasis. Methods In this multicenter, double-blind, placebo-controlled trial, 249 patients with severe plaque psoriasis were randomly assigned to receive intravenous infusions of either 3 or 5 mg/kg of infliximab or placebo given at weeks 0, 2, and 6. The primary end point was the proportion of patients who achieved at least 75% improvement in Psoriasis Area and Severity Index score from baseline at week 10. At week 26, patients whose Physician Global Assessment indicated moderate or severe disease were eligible for a single intravenous infusion of their assigned treatment to assess the safety of retreatment after a 20-week, treatment-free interval. Results At week 10, 72% of patients treated with infliximab (3 mg/kg) and 88% of patients treated with infliximab (5 mg/kg) achieved a 75% or greater improvement from baseline in Psoriasis Area and Severity Index score compared with 6% of patients treated with placebo ( P Conclusions Infliximab treatment resulted in a rapid and significant improvement in the signs and symptoms of psoriasis. Infliximab was generally well tolerated.
TL;DR: Spasticity VAS scores were significantly reduced by CBME (Sativex) in comparison with placebo (P- 0.001), there were no significant adverse effects on cognition or mood and intoxication was generally mild.
Abstract: The objective was to determine whether a cannabis-based medicinal extract (CBME) benefits a range of symptoms due to multiple sclerosis (MS). A parallel group, double-blind, randomized, placebo-controlled study was undertaken in three centres, recruiting 160 outpatients with MS experiencing significant problems from at least one of the following: spasticity, spasms, bladder problems, tremor or pain. The interventions were oromucosal sprays of matched placebo, or whole plant CBME containing equal amounts of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) at a dose of 2.5-120 mg of each daily, in divided doses. The primary outcome measure was a Visual Analogue Scale (VAS) score for each patient's most troublesome symptom. Additional measures included VAS scores of other symptoms, and measures of disability, cognition, mood, sleep and fatigue. Following CBME the primary symptom score reduced from mean (SE) 74.36 (11.1) to 48.89 (22.0) following CBME and from 74.31 (12.5) to 54.79 (26.3) following placebo [ns]. Spasticity VAS scores were significantly reduced by CBME (Sativex) in comparison with placebo (P =0.001). There were no significant adverse effects on cognition or mood and intoxication was generally mild.
TL;DR: Venlafaxine ER appears effective and safe in relieving pain associated with diabetic neuropathy and NNT values for higher dose venlafAXine ER are comparable to those of tricyclic antidepressants and the anticonvulsant gabapentin.
Abstract: To evaluate the efficacy and safety of 6 weeks of venlafaxine extended-release (ER) (75 mg and 150-225 mg) treatment in patients with painful diabetic neuropathy. This multicenter, double-blind, randomized, placebo-controlled study included 244 adult outpatients with metabolically stable type 1 or 2 diabetes with painful diabetic neuropathy. Primary efficacy measures were scores on the daily 100 mm Visual Analog Pain Intensity (VAS-PI) and Pain Relief (VAS-PR) scales. Secondary efficacy measures included the Clinical Global Impressions-Severity of Illness and the Clinical Global Impressions-Improvement, Patient Global Rating of Pain Relief, and percentage of patients achieving 50% reduction in pain intensity. Baseline pain intensity was 68.7 mm (moderately severe). At week 6, the percentage reduction from baseline in VAS-PI was 27% (placebo), 32% (75 mg), and 50% (150-225 mg; P < 0.001 vs placebo). Mean VAS-PR scores in the 150-225 mg group were significantly greater than placebo at week 6 (44 vs 60 mm; P < 0.001). The number needed to treat (NNT) for 50% pain intensity reduction with venlafaxine ER 150-225 mg was 4.5 at week 6. Nausea and somnolence were the most common treatment-emergent adverse events. Seven patients on venlafaxine had clinically important ECG changes during treatment. Venlafaxine ER appears effective and safe in relieving pain associated with diabetic neuropathy. NNT values for higher dose venlafaxine ER are comparable to those of tricyclic antidepressants and the anticonvulsant gabapentin.
TL;DR: Laroscopic excision of endometriosis is more effective than placebo at reducing pain and improving quality of life, and surgery is associated with a 30% placebo response rate that is not dependent on severity of disease.
TL;DR: Repeat doses of aerosolized adeno-associated serotype 2 vector containing cystic fibrosis transmembrane conductance regulator (CFTR) complementary DNA (cDNA) tgAAVCF were safe and well tolerated, and resulted in encouraging trends in improvement in pulmonary function in patients with CF and mild lung disease.
TL;DR: Disulfiram seems to exert a direct effect on cocaine use rather than through reducing concurrent alcohol use, and CBT and IPT are effective therapies for general populations of cocaine-dependent individuals.
Abstract: Context Disulfiram has emerged as a promising treatment for cocaine dependence, but it has not yet been evaluated in general populations of cocaine users. Objectives To compare the effectiveness of disulfiram therapy with that of a placebo condition in reducing cocaine use and to compare the effectiveness of 2 active behavioral therapies—cognitive behavior therapy (CBT) and interpersonal psychotherapy (IPT)—in reducing cocaine use. Design Randomized, placebo-controlled, double-masked (for medication condition), factorial (2 × 2) trial with 4 treatment conditions: disulfiram plus CBT, disulfiram plus IPT, placebo plus CBT, and placebo plus IPT. Setting A community-based outpatient substance abuse treatment program. Patients A total of 121 individuals meeting the criteria for current cocaine dependence. Interventions Patients received either disulfiram (250 mg/d) or placebo in identical capsules. Medication compliance was monitored using a riboflavin marker procedure. Both behavioral therapies (CBT and IPT) were manual guided and were delivered in individual sessions for 12 weeks. Main Outcome Measures Random regression analyses of self-reported frequency of cocaine use and results of urine toxicology screens. Results Participants assigned to disulfiram reduced their cocaine use significantly more than those assigned to placebo, and those assigned to CBT reduced their cocaine use significantly more than those assigned to IPT ( P Conclusions Disulfiram and CBT are effective therapies for general populations of cocaine-dependent individuals. Disulfiram seems to exert a direct effect on cocaine use rather than through reducing concurrent alcohol use.
TL;DR: In untreated dyslipidaemic patients with CHD and normal renal function at baseline, CrCl declines over a period of three years and statin treatment prevents this decline and significantly improves renal function, potentially offsetting an additional factor associated withCHD risk.
Abstract: It has been reported recently that of 4483 apparently healthy men participating in the physicians’ health study with an initial serum creatinine (SCr) < 115 µmol/litre (13 mg/litre), those with low high density lipoprotein (HDL) cholesterol and high non-HDL cholesterol had double the risk of renal insufficiency, during longterm follow up, after adjusting for other risk factors.1 Although studies in animal models have found a favourable effect of lipid reduction on the progression of renal disease,2–4 the results of trials in humans are less clear, because most controlled trials have been too small to make a definitive conclusion.5 The Helsinki heart study,6 a primary prevention trial, was the first survival study with hypolipidaemic drug treatment to address the issue. Authors reported that dyslipidaemia increased SCr values in patients with normal baseline renal function, both in the placebo and gemfibrozil subgroups, suggesting that treatment with a fibrate could not prevent the deterioration of renal function. Fibrates may increase SCr concentrations, although gemfibrozil, which was used in the Helsinki heart study, usually does not exert this adverse effect.7
“Although studies in animal models have found a favourable effect of lipid reduction on the progression of renal disease, the results of trials in humans are less clear, because most controlled trials have been too small to make a definitive conclusion”
The recently published MRC/BHF heart protection study (HPS) subgroup analysis for participants with diabetes mellitus8 showed that unadjusted SCr concentrations increased in all patients, with or without diabetes mellitus, over a period of 4.6 years. However, allocation to simvastatin (40 mg/day) significantly decreased the rise in SCr values in patients with and without diabetes mellitus.8
The Greek atorvastatin and coronary heart disease evaluation (GREACE) study,9,10 a prospective, randomised, target based, open label secondary coronary heart disease (CHD) prevention trial, suggested that structured management of dyslipidaemia with dose titration of atorvastatin can achieve the national cholesterol educational programme (NCEP) treatment goals11,12 and provide significant reductions in morbidity and mortality, in comparison with usual care. In the present subgroup analysis of the GREACE results, we report the longterm effect of structured versus usual care (intention to treat analysis), and the effect of statin versus no hypolipidaemic drug treatment (treatment based analysis) on estimated creatinine clearance (CrCl).
TL;DR: The results suggest that children of all ages with clinical features of HIV infection should receive co-trimoxazole prophylaxis in resource-poor settings, irrespective of local resistance to this drug.
TL;DR: Endothelin(A) blockade with darusentan did not improve cardiac remodelling or clinical symptoms or outcomes in patients with chronic heart failure receiving an angiotensin-converting-enzyme inhibitor, beta blocker, or aldosterone antagonist, and is unlikely to be useful as an add-on treatment in such patients.
TL;DR: A large number of animals have shown remission of ulcerative colitis following treatment with probiotics, and these animals have also shown the ability to tolerate high levels of antibiotics.
Abstract: Summary
Background : Probiotics are efficacious for treating and maintaining remission of ulcerative colitis.
Aim : To conduct a randomized placebo-controlled trial of bifidobacteria-fermented milk supplementation as a dietary adjunct in treating active ulcerative colitis.
Methods : Twenty patients with mild to moderate, active, ulcerative colitis randomly received 100 mL/day of bifidobacteria-fermented milk or placebo for 12 weeks with conventional treatment.
Results : Clinical and endoscopic activity indices and histological scores were similar in the two groups before treatment. Although improvements were significant in both groups, the clinical activity index was significantly lower in the bifidobacteria-fermented milk than in the placebo group after treatment. The post-treatment endoscopic activity index and histological score were significantly reduced in the bifidobacteria-fermented milk, but not the placebo group. Increases in faecal butyrate, propionate and short-chain fatty acid concentrations were significant in the bifidobacteria-fermented milk, but not the placebo group. No adverse effects were observed in either group.
Conclusion : Supplementation with this bifidobacteria-fermented milk product is safe and more effective than conventional treatment alone, suggesting possible beneficial effects in managing active ulcerative colitis. This is a pilot study and further larger studies are required to confirm the result these preliminary results.
TL;DR: This study confirms previous observations from a dose-ranging study showing that anakinra, in combination with MTX, is an effective and safe treatment for patients with RA who have inadequate responses to MTX alone.
Abstract: Objective: To assess the efficacy and safety of 100 mg daily anakinra (Kineret), a recombinant form of the naturally occurring interleukin 1 receptor antagonist, plus methotrexate (MTX) in reducing the signs and symptoms of rheumatoid arthritis (RA).
Methods: Patients with active RA (n = 506) despite current treatment with MTX were enrolled in this multicentre, double blind, randomised, placebo controlled study. Patients received subcutaneous injections of anakinra 100 mg/day or placebo. They were assessed monthly for 6 months for improvement in signs and symptoms of RA and for adverse events. The primary efficacy measure was the percentage of patients attaining ACR20 response at week 24.
Results: Significantly greater proportions of patients treated with anakinra compared with placebo achieved ACR20 (38% v 22%; p<0.001), ACR50 (17% v 8%; p<0.01), and ACR70 (6% v 2%; p<0.05) responses. The response to anakinra was rapid; the proportion of patients with an ACR20 response at the first study assessment (4 weeks) was twice as high with anakinra as with placebo (p<0.005). Clinically meaningful and statistically significant responses were also seen in individual components of the ACR response (for example, Health Assessment Questionnaire, pain, C reactive protein levels, and erythrocyte sedimentation rate). Anakinra was well tolerated, with a safety profile, similar to that of placebo with one exception: mild to moderate injection site reactions were more common with anakinra than with placebo (65% v 24%).
Conclusions: This study confirms previous observations from a dose-ranging study showing that anakinra, in combination with MTX, is an effective and safe treatment for patients with RA who have inadequate responses to MTX alone.
TL;DR: A preliminary randomized, placebo-controlled trial to determine the safety and antidepressant efficacy of pramipexole in treatment-resistant bipolar depression found it was a safe and effective antidepressant among patients with bipolar depression.
Abstract: OBJECTIVE: Previous studies suggest that the dopamine agonist pramipexole may possess antidepressant properties. The authors conducted a preliminary randomized, placebo-controlled trial to determine the safety and antidepressant efficacy of pramipexole in treatment-resistant bipolar depression. METHOD: Twenty-two depressed outpatients with DSM-IV nonpsychotic bipolar disorder were randomly assigned to receive placebo or flexibly dosed pramipexole (mean maximum dose=1.7 mg/day, SD=1.3) added to existing mood stabilizers for 6 weeks. The primary outcome measure was response, defined as improvement in Hamilton Depression Rating Scale score of 50% or more over the baseline score; secondary analyses involved changes in Clinical Global Impression (CGI) severity scores. RESULTS: More patients given pramipexole (10 [83%] of 12) than patients given placebo (six [60%] of 10) completed the study. Eight (67%) of 12 patients taking pramipexole and two (20%) of 10 taking placebo had an improvement of at least 50% in th...
TL;DR: Etanercept is a well tolerated and effective treatment for reducing clinical symptoms and signs of ankylosing spondylitis.
Abstract: Objective: A double blind, randomised, placebo controlled study to evaluate the safety and efficacy of etanercept to treat adult patients with ankylosing spondylitis (AS). Methods: Adult patients with AS at 14 European sites were randomly assigned to 25 mg injections of etanercept or placebo twice weekly for 12 weeks. The primary efficacy end point was an improvement of at least 20% in patient reported symptoms, based on the multicomponent Assessments in Ankylosing Spondylitis (ASAS) response criteria (ASAS 20). Secondary end points included ASAS 50 and ASAS 70 responses and improved scores on individual components of ASAS, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), acute phase reactants, and spinal mobility tests. Safety was evaluated during scheduled visits. Results: Of 84 patients enrolled, 45 received etanercept and 39 received placebo. Significantly more etanercept patients than placebo patients responded at the ASAS 20 level as early as week 2, and sustained differences were evident up to week 12. Significantly more etanercept patients reported ASAS 50 responses at all times and ASAS 70 responses at weeks 2, 4, and 8; reported lower composite and fatigue BASDAI scores; had lower acute phase reactant levels; and had improved spinal flexion. Etanercept was well tolerated. Most adverse events were mild to moderate; the only between-group difference was injection site reactions, which occurred significantly more often in etanercept patients. Conclusions: Etanercept is a well tolerated and effective treatment for reducing clinical symptoms and signs of AS.
TL;DR: Treatment with citalopram reduced depressive symptoms to a significantly greater extent than placebo treatment and was well tolerated in this population of children and adolescents.
Abstract: OBJECTIVE: Open-label trials with the selective serotonin reuptake inhibitor citalopram suggest that this agent is effective and safe for the treatment of depressive symptoms in children and adolescents. The current study investigated the efficacy and safety of citalopram compared with placebo in the treatment of pediatric patients with major depression. METHOD: An 8-week, randomized, double-blind, placebo-controlled study compared the safety and efficacy of citalopram with placebo in the treatment of children (ages 7–11) and adolescents (ages 12–17) with major depressive disorder. Diagnosis was established with the Schedule for Affective Disorders and Schizophrenia for School-Age Children—Present and Lifetime Version. Patients (N=174) were treated initially with placebo or 20 mg/day of citalopram, with an option to increase the dose to 40 mg/day at week 4 if clinically indicated. The primary outcome measure was score on the Children’s Depression Rating Scale—Revised; the response criterion was defined as...
TL;DR: Although significant treatment effects were not seen in the primary efficacy measures, outcomes on secondary measures suggest promising directions for further evaluation of donepezil treatment in patients with MCI.
Abstract: Objective: To evaluate the efficacy and safety of the acetylcholinesterase inhibitor donepezil in a placebo-controlled trial in patients with mild cognitive impairment (MCI). Methods: A total of 270 patients with MCI were enrolled in a 24-week, multicenter, randomized, double-blind, placebo-controlled study. Patients were randomized to receive donepezil (n = 133; 5 mg/day for 42 days, followed by forced dose escalation to 10 mg/day) or placebo (n = 137). Primary efficacy measures were the New York University (NYU) Paragraph Delayed Recall test and the Alzheimer disease (AD) Cooperative Study Clinician’s Global Impression of Change for MCI (ADCS CGIC-MCI). Secondary efficacy measures included the modified AD Assessment Scale-cognitive subscale (ADAS-cog), the Patient Global Assessment (PGA), and additional neuropsychologic measures. Efficacy analyses were performed on intent-to-treat (ITT) and fully evaluable (FE) populations. Results: Primary efficacy measures of the NYU Paragraph Recall test and the ADCS CGIC-MCI did not show significant treatment effects in the ITT population. Some secondary measures showed effects favoring donepezil. More donepezil-treated patients showed improvements in ADAS-cog total scores, in tests of attention and psychomotor speed, and in PGA scores. More donepezil-treated than placebo-treated patients experienced adverse events, most of which were mild to moderate and transient. Conclusion: Although significant treatment effects were not seen in the primary efficacy measures, outcomes on secondary measures suggest promising directions for further evaluation of donepezil treatment in patients with MCI.
Journal Article•
TL;DR: Ropinirole improves restless legs syndrome compared with placebo, with benefits apparent by week 1, and is generally well tolerated.
Abstract: Objective: To assess the efficacy, safety, and tolerability of ropinirole in the treatment of patients with restless legs syndrome. Methods: A 12 week, prospective, double blind, randomised comparison involving 284 patients from 10 European countries. All participants had a score of ⩾15 on the international restless legs scale (IRLS). Patients were randomised (1:1) to receive either ropinirole 0.25–4.0 mg once daily or placebo. The primary efficacy end point was mean change from baseline to week 12 in total IRLS score. Global improvements (clinical global impression (CGI) scale) and improvements in sleep, health related quality of life (QoL; using generic and disease specific measures), work, and other activities were also assessed. Results: 112/146 patients (76.7%) taking ropinirole and 109/138 (79.0%) taking placebo completed the study. Improvement in IRLS at week 12 with ropinirole (mean (SD) dose, 1.90 (1.13) mg/day) was greater than with placebo (mean (SE): −11.04 (0.719) v −8.03 (0.738) points; adjusted difference = −3.01 (95% confidence interval (CI), −5.03 to −0.99); p = 0.0036). More patients in the ropinirole group (53.4%) showed improvement on the CGI scale at week 12 than in the placebo group (40.9%; adjusted odds ratio = 1.7 (1.02 to 2.69); p = 0.0416). Significant differences on both IRLS and CGI scales favouring ropinirole were apparent by week 1. Ropinirole was also associated with significantly greater improvements in sleep and QoL end points. The most common adverse events were nausea and headache. Conclusions: Ropinirole improves restless legs syndrome compared with placebo, with benefits apparent by week 1. It is generally well tolerated.
TL;DR: Clozapine at a mean dose lower than 50 mg/day improves drug induced psychosis in PD without significant worsening of motor function, and the effect wears off once the treatment stops.
Abstract: Objective: To compare the efficacy and safety of clozapine in drug induced psychosis in Parkinson’s disease (PD). Methods: A four week, randomised, double blind, parallel comparison of clozapine and placebo, followed by a 12 week clozapine open period, plus a one month period after drug discontinuation, in 60 patients with PD. The primary efficacy outcome was the “clinical global impression scale” (CGI); the positive subscore of the “positive and negative syndrome scale” (PANSS) was used as the secondary efficacy parameter and the “unified Parkinson’s disease rating scale” (UPDRS) and the “mini mental test examination” (MMSE) as safety outcomes. Results: The mean (SD) dosage of clozapine was 35.8 (12.5–50) mg at the end of the double blind period. The mean (SD) scores on the CGI improved by 1.8 (1.5) for the clozapine group compared with 0.6 (1.1) for the placebo group (p = 0.001). The mean (SD) positive subscore of PANSS improved by 5.6 (3.9) for the clozapine group (0.8 (2.8) for the placebo group; p Conclusions: Clozapine at a mean dose lower than 50 mg/day improves drug induced psychosis in PD without significant worsening of motor function, and the effect wears off once the treatment stops.
TL;DR: Long-term treatment (up to 5 years) with soy phytoestrogens was associated with an increased occurrence of endometrial hyperplasia, calling into question the long-term safety of phy toestrogens with regard to the endometrium.