Placebo-controlled Study (placebo-controlled + study)

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Selected Abstracts

A double blind, randomized, placebo controlled study to evaluate the efficacy of erythromycin in patients with knee effusion due to osteoarthritis

Abstract Objective:, The efficacy of erythromycin in treatment of knee effusion due to osteoarthritis was evaluated. Method:, We assessed efficacy and safety of erythromycin during 16 weeks in patients enrolled in a randomized double-blind study. One hundred and eight patients with knee effusion due to osteoarthritis (OA) received 12-week courses of erythromycin or placebo allocated randomly, and were followed for 4 months. Acetaminophen 650 mg/day was used in both groups, while they received no other anti-inflammatory drugs (such as corticosteroid or nonsteroidal anti-inflammatory drugs) during the course of the study. Our patients were divided in two groups, erythromycin in doses of 200 mg four times per day was given to the first group (51 patients) over the first 3 months of the study and in the second group we used placebo with the same dosage and schedule (53 patients). Outcomes improvement for the erythromycin-treated group was assessed by a significantly higher mean score from baseline to the end of the trial, compared with placebo group. Patients were examined monthly during the treatment period. Measurement values included recording of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire subscales (pain, stiffness and function), range of motion and knee circumference. Results:, Erythromycin produced a higher response rate than placebo in treatment of knee effusion due to OA. Significant reduction in knee circumference (P < 0.0005) and pain (P < 0.001) with functional improvement (P < 0.0005) were seen. At the first month after treatment, 11.8% (6 patients) in erythromycin and 9.4% (5 patients) in placebo groups had 50% pain reduction, which was not significant (P = 0.75). At the fourth month, 50% reduction of pain was seen in 45.1% (23 patients) of the erythromycin and 11.3% (6 patients) of the placebo group. This was statistically significant (P < 0.0005). Erythromycin treatment was well tolerated and mild adverse events caused no discontinuation during the study. Conclusion:, This is a placebo-controlled study of macrolid efficacy on knee effusion due to OA in a short period. Results of this research showed the better efficacy of erythromycin in controlling effusion and pain with functional improvement in patients with knee effusion due to OA. [source]

Effect of oral melatonin on the procoagulant response to acute psychosocial stress in healthy men: a randomized placebo-controlled study

Petra H. Wirtz
Abstract:, Acute mental stress is a potent trigger of acute coronary syndromes. Catecholamine-induced hypercoagulability with acute stress contributes to thrombus growth after coronary plaque rupture. Melatonin may diminish catecholamine activity. We hypothesized that melatonin mitigates the acute procoagulant stress response and that this effect is accompanied by a decrease in the stress-induced catecholamine surge. Forty-five healthy young men received a single oral dose of either 3 mg melatonin (n = 24) or placebo medication (n = 21). One hour thereafter, they underwent a standardized short-term psychosocial stressor. Plasma levels of clotting factor VII activity (FVII:C), FVIII:C, fibrinogen, D-dimer, and catecholamines were measured at rest, immediately after stress, and 20 min and 60 min post-stress. The integrated change in D-dimer levels from rest to 60 min post-stress differed between medication groups controlling for demographic and metabolic factors (P = 0.047, = 0.195). Compared with the melatonin group, the placebo group showed a greater increase in absolute D-dimer levels from rest to immediately post-stress (P = 0.13; = 0.060) and significant recovery of D-dimer levels from immediately post-stress to 60 min thereafter (P = 0.007; = 0.174). Stress-induced changes in FVII:C, FVIII:C, fibrinogen, and catecholamines did not significantly differ between groups. Oral melatonin attenuated the stress-induced elevation in the sensitive coagulation activation marker D-dimer without affecting catecholamine activity. The finding provides preliminary support for a protective effect of melatonin in reducing the atherothrombotic risk with acute mental stress. [source]

Oral melatonin reduces blood coagulation activity: a placebo-controlled study in healthy young men

Petra H. Wirtz
Abstract:, Melatonin has previously been suggested to affect hemostatic function but studies on the issue are scant. We hypothesized that, in humans, oral administration of melatonin is associated with decreased plasma levels of procoagulant hemostatic measures compared with placebo medication and that plasma melatonin concentration shows an inverse association with procoagulant measures. Forty-six healthy men (mean age 25 4 yr) were randomized, single-blinded, to either 3 mg of oral melatonin (n = 25) or placebo medication (n = 21). One hour thereafter, levels of melatonin, fibrinogen, and D-dimer as well as activities of coagulation factor VII (FVII:C) and VIII (FVIII:C) were measured in plasma. Multivariate analysis of covariance and regression analysis controlled for age, body mass index, mean arterial blood pressure, heart rate, and norepinephrine plasma level. Subjects on melatonin had significantly lower mean levels of FVIII:C (81%, 95% CI 71,92 versus 103%, 95% CI 90,119; P = 0.018) and of fibrinogen (1.92 g/L, 95% CI 1.76,2.08 versus 2.26 g/L, 95% CI 2.09,2.43; P = 0.007) than those on placebo explaining 14 and 17% of the respective variance. In all subjects, increased plasma melatonin concentration independently predicted lower levels of FVIII:C (P = 0.037) and fibrinogen (P = 0.022) explaining 9 and 11% of the respective variance. Melatonin medication and plasma concentration were not significantly associated with FVII:C and D-dimer levels. A single dose of oral melatonin was associated with lower plasma levels of procoagulant factors 60 min later. There might be a dose,response relationship between the plasma concentration of melatonin and coagulation activity. [source]

Clinical trial: the efficacy and safety of oral PF-03491390, a pancaspase inhibitor , a randomized placebo-controlled study in patients with chronic hepatitis C

Aliment Pharmacol Ther,31, 969,978 Summary Background, Elevated serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) reflect hepatocellular injury in patients with chronic hepatitis C virus (HCV). Increased apoptosis and activated caspases are present in these patients. PF-03491390 inhibits multiple caspases and lowers serum AST and ALT levels in patients with chronic liver diseases. Aim, To determine if treatment with an oral pancaspase inhibitor could reduce serum AST and ALT in patients with HCV. Methods, Double-blind, randomized, placebo-controlled, parallel-dose study in 204 patients treated with placebo or PF-03491390 (5, 25 or 50 mg) orally twice daily (b.d.) for up to 12 weeks. Serum AST and ALT were monitored weekly. Results, Significant reductions in serum AST and ALT were observed within 1 week of initiating PF-03491390 in all treatment groups (P < 0.0001). These reductions in AST and ALT were maintained throughout the 12 week treatment period and returned to baseline levels when PF-03491390 was discontinued. Increasing the dose did not further lower AST or ALT. The most frequently reported adverse events were headache and fatigue. Conclusion, PF-03491390 significantly reduced serum AST and ALT levels in patients with chronic HCV, and was well tolerated over 12 weeks. [source]

Modafinil treatment of fatigue in patients with ALS: A placebo-controlled study

MUSCLE AND NERVE, Issue 3 2009
Judith G. Rabkin PhD
Abstract Our objective was to determine whether modafinil alleviates fatigue in patients with amyotrophic lateral sclerosis (ALS). A placebo controlled trial with a 3:1 modafinil:placebo randomization in doses up to 300 mg/day for 4 weeks was followed by 8 weeks of open maintenance treatment. The primary endpoint was the Clinical Global Impressions-Improvement Scale. Secondary endpoints were the Fatigue Severity Scale, Epworth Sleepiness Scale, Beck Depression Inventory, Role Function Scale, and visual analog scales. Analysis of covariance was used to assess change at Week 4. Thirty-two patients were randomized; 29 completed the 4-week trial. In intention to treat (ITT) analysis, the response was 76% for modafinil versus 14% for placebo. In a completer analysis, the modafinil response rate was 86%, and the placebo response rate remained 14%. The number needed to treat was 1.6 (ITT). No medically serious adverse events were reported. Modafinil may be a promising intervention for fatigue in ALS patients. Replication in a larger study is needed. Muscle Nerve 39: 297,303, 2009 [source]

Latest news and product developments

PRESCRIBER, Issue 4 2007
Article first published online: 3 APR 200
Low-dose aspirin may reduce asthma risk Low-dose aspirin may reduce the risk of new-onset asthma, according to a US analysis (Am J Respir Crit Care Med 2007;175:120-5). Prompted by speculation of such a link, the authors conducted a post-hoc analysis of the Physicians' Health Study, a placebo-controlled study of aspirin 325mg on alternate days involving 22 071 men aged 40-84. The risk of developing a new diagnosis of asthma during the five-year study was reduced by 22 per cent (p=0.045) among those taking aspirin. However, the number of cases was low: 113 among aspirin recipients and 145 with placebo. The clinical importance of this finding is therefore uncertain, though it received wide coverage in the lay media. Lifestyle changevsdrugs in type 2 diabetes Modifying lifestyle is at least as effective as drugs in delaying the onset of type 2 diabetes in people with impaired glucose tolerance, according to a study from Leicester (BMJ online. doi: 10.1136/bmj.39063.689375.55). The meta-analysis of 17 trials involving 8084 participants found that lifestyle change or orlistat approximately halved the risk of progressing to diabetes, whereas oral hypoglycaemic agents reduced the risk by 30 per cent. A Chinese herb, jiang tang bushen, reduced the risk by two-thirds. The analysis was conducted before the findings of major trials of rosiglitazone (Avandia) , DREAM and ADOPT , were published. Optician prescribing The diagnosis and treatment of disorders such as conjunctivitis by opticians is to be an enhanced service that PCTs can commission according to local need, a Department of Health review has concluded. The General Ophthalmic Services Review considered new arrangements to support PCTs provide ophthalmic services. Professional representatives proposed that the diagnosis and treatment of some eye conditions should be classed as ,additional services' that PCTs should be obliged to commission. While the Department agreed that opticians can play an important role, it found a lack of evidence of benefits and concluded that PCTs should be able to determine their level of services. A commissioning toolkit has been produced to help implement the review's findings. Warfarin stroke risk A four-fold increase in warfarin use has been linked with an increased incidence of intracerebral haemorrhage in a US study (Neurology 2007;68:116-21). Reviewing all first admissions for haemorrhagic stroke in the Cincinnati area, the study found that the proportion of cases associated with warfarin or heparin increased from 5 per cent in 1988 to 9 per cent in 1993/94 and 17 per cent in 1999. The annual incidence among patients aged 80 or older increased from 2.5 to 46 per 100 000 from 1988 to 1999. During the same period, warfarin distribution increased four-fold and there was no change in the incidence of thromboembolic strokes. Co-proxamol will go, MHRA reaffirms The MHRA has confirmed that it still intends to withdraw co-proxamol from the market despite protestations from MPs. The issue was raised by two MPs , one a member of the Health Select Committee , in a House of Commons debate. Both called for the withdrawal process to be abandoned, arguing that GPs should have the right to prescribe a drug for which there may be no alternative. The MHRA has restated its view that the risk from overdose with co-proxamol outweighs its benefits, adding: ,The avoidable death toll from co-proxamol overdose cannot be ignored. Sometimes regulation has to balance the needs of the individual against the benefits at a population level. In this case the removal of marketing authorisations with continued use possible in exceptional circumstances is the best balance that could be achieved. The public health gain is already becoming apparent.' Co-proxamol may still be prescribed as an unlicensed drug after its product licence is withdrawn at the end of this year. Guide to pharmacy services A guide to community pharmacy services has been published for patients, carers and members of patient organisations. Developed by the South East Local Pharmaceutical Committee Forum, Understanding and Making the Best Use of Community Pharmacy explains what pharmacies offer and the services available under the 2005 pharmacy contract. Copies can be downloaded from Little benefit from opioids for back pain There is little evidence that opioids relieve chronic back pain but the risk of abuse is high, according to a US analysis (Ann Intern Med 2007;146:116-27). The systematic review of trials of oral, topical and transdermal opioids in the treatment of chronic back pain found no trials lasting more than 16 weeks. There was no significant reduction in pain in placebo-controlled trials and limited, nonsignificant pain reductions in comparative trials. By contrast, estimates of prevalence of current substance misuse were as high as 43 per cent and that of ,aberrant medication-taking behaviours' ranged from 5 to 24 per cent. Dual antiplatelet therapy with drug-eluting stents Patients with drug-eluting stents should not stop dual antiplatelet therapy prematurely (Circulation 2007; published online 15 January; DOI: 10.1161/CIRCUL ATIONAHA.106.180944). Although 12 months' treatment with low-dose aspirin plus a thienopyri- dine, eg clopidogrel (Plavix) and ticlopidine, has been shown to reduce cardiac events after implanting a drug-eluting stent, it is not uncommon for the thienopyridine to be discontinued. Health professionals must do more to educate patients about their treatment and the risks associated with stopping. Scottish approval The SMC ( has approved varenicline (Champix) for use within NHS Scotland as part of a smoking cessation programme; it notes that the benefits of extending a course of treatment beyond the initial 12 weeks are modest. Controversially, the SMC has not approved omalizumab (Xolair) as add-on therapy for severe persistent allergic asthma on the grounds that an economic case had not been made. Asthma UK criticised the decision as unjust and inhumane. NICE is due to publish an appraisal of omalizumab later this year. No decline with anti- psychotics Treatment with anti- psychotics does not hasten cognitive decline in patients with Alzheimer's disease, say investigators from London (J Neurol Neurosurg Psychiatry 2007;78:25-9). Their prospective study of 224 patients found no difference in the rate of cognitive decline in those treated with antipsychotics (atypical or otherwise) for at least six months. Label translation online Health IT consultancy Rxinfo has developed a website offering translations of the most common types of labelling. The site ( offers translations into 13 Asian and European languages for 15 standard labelling phrases covering oral medicines and ENT formulations. A free application can be downloaded to allow direct-to-printer printing. Copyright 2007 Wiley Interface Ltd [source]

Effect of fluvastatin on cardiac outcomes in kidney transplant patients with systemic lupus erythematosus: A randomized placebo-controlled study,

Gudrun E. Norby
Objective Patients with systemic lupus erythematosus (SLE), with or without end-stage renal failure, are at increased risk of premature cardiovascular disease. Although statin therapy has been found to reduce cardiovascular risk in the general population, its effectiveness in kidney transplant recipients with SLE has not been examined. This study was undertaken to investigate the effect of fluvastatin on cardiac end points in a randomized controlled trial of renal transplant patients with SLE. Methods Patients with SLE were identified from among participants in the Assessment of Lescol in Renal Transplantation trial, a randomized, double-blind, placebo-controlled study of the effect of fluvastatin (40,80 mg/day) on cardiovascular outcomes in renal transplant recipients. Patients were randomized to either a group receiving fluvastatin or a placebo group for the duration of the 5,6-year trial, and then invited to continue in a 2-year open-label extension during which all participants, regardless of original group, received fluvastatin. Patients were followed up for a total of 7,8 years for assessment of the primary end point of major cardiac events, comprising nonfatal myocardial infarction, cardiac death, and coronary intervention procedures. Results Fluvastatin reduced low-density lipoprotein cholesterol levels by 29.2% (95% confidence interval [95% CI] 18.3,40%), from a mean SD of 4.0 0.9 mmoles/liter to 2.8 1.1 mmoles/liter, and total cholesterol by 19.6% (95% CI 11.7,27.5%), from 6.4 0.9 mmoles/liter to 5.1 1.1 mmoles/liter. Compared with placebo-treated patients, patients randomized to receive fluvastatin exhibited a 73.4% reduction in the risk of major cardiac events (relative risk 26.6 [95% CI 5.9,119.4], P = 0.064). Conclusion Our results indicate that the effect of fluvastatin on cardiac events in renal transplant recipients with SLE is similar to that observed with statin therapy in the renal transplant population as a whole. [source]

Effects of lamotrigine in patients with bipolar disorder and alcohol dependence

Gabriel Rubio
Background:, Bipolar disorder is significantly associated with alcohol use disorders. Anticonvulsant drugs are used in the treatment of bipolar disorder and they have also been used to treat alcohol dependence. The purpose of the present study was to evaluate tolerance and safety of lamotrigine in a dual-diagnosis population presenting bipolar disorder and alcohol dependence. Open-label lamotrigine was examined in 28 outpatients with DSM-IV bipolar disorder and alcohol dependence. Lamotrigine was added to existing medication regimens. Method:, Lamotrigine was started at a dose of 25 mg/day and titrated to a maximum dose of 300 mg/day. Subjects received a baseline evaluation which included a Structured Clinical Interview for DSM-IV (SCID) and weekly assessments for 12 weeks with the Hamilton Rating Scale for Depression (HAM-D), Young Mania Rating Scale (YMRS), Brief Psychiatric Rating Scale (BPRS), Severity of Alcohol Dependence Scale (SADS), a Visual Analogue Scale for Craving severity (VASC), and alcohol consumption. The concentration of carbohydrate-deficient transferrin (CDT) was used as an indirect measure of alcohol consumption. The sample consisted of 18 men and 10 women diagnosed with alcohol dependence and bipolar disorder I (n = 21) or bipolar disorder II (n = 7), with a mean age of 36.5 7.7 years. Results:, Significant improvement was observed in HAM-D, YMRS, and BPRS scores (p < 0.01). Craving and CDT also significantly decreased (p < 0.001). Lamotrigine was well tolerated with no dropout subjects due to adverse events. Conclusion:, Lamotrigine is safe and well tolerated in this sample and associated with improvement in mood, alcohol craving and alcohol consumption. A placebo-controlled study would be of interest. [source]

Effects of high-dose sublingual immunotherapy on quality of life in patients with cypress-induced rhinitis: a placebo-controlled study

V. Di Rienzo
Summary The efficacy of specific immunotherapy and particularly of sublingual immunotherapy (SLIT) in subjects allergic to Cupressaceae pollen is well defined, but no study assessed its effects on quality of life (QoL). We evaluated the effectiveness of SLIT with a standardized, high-dose extract of Juniperus ashei in patients with cypress-induced rhinitis, using QoL as the major outcome measure. Thirty-four patients, 20 males and 14 females, mean age 33.8 years, with allergic rhinitis (AR) from cypress pollen were randomly assigned to receive an allergen extract standardized in index of reactivity (IR) of J. ashei (19 patients) or a placebo (15 patients). The schedule was pre-coseasonal, with a build-up phase in 12 days and a maintenance treatment with 300 IR a day up to the end of the cypress pollen season. All patients registered in diary cards their symptoms, drug consumption and side-effects. The QoL was measured before and after SLIT by the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) by Juniper during the peak of the cypress pollen season. QoL significantly improved in respect to baseline in actively (P=0.017) but not in placebo-treated patients, and there was a significant difference in favour of actively treated patients during the pollen season (P=0.02). Actively and placebo-treated patients had comparable symptom,medication scores in the period from 15 February to 15 March, corresponding to the peak pollen season, but placebo-treated patients showed an uneven drug consumption compared with actively treated patients. Side-effects were relatively common, but mostly with local short-lasting symptoms, and no systemic reaction was reported. These findings show that SLIT with high doses of J. ashei in subjects with cypress-induced rhinitis significantly improves QoL and confirm previous observations on the disagreement between QoL , which assesses patient's perception , and medical parameters used in trials. [source]

Multiple doses of secretin in the treatment of autism: a controlled study

E Sponheim
Dramatic effects on autistic behaviour after repeated injections of the gastrointestinal hormone secretin have been referred in a number of case reports. In the absence of curative and effective treatments for this disabling condition, this information has created new hope among parents. Although controlled studies on the effect of mainly one single dose have not documented any effect, many children still continue to receive secretin. Six children enrolled in a double-blind, placebo-controlled crossover study in which each child was its own control. Human synthetic secretin, mean dose 3.4 clinical units, and placebo were administered intravenously in randomized order every 4th wk, on three occasions each. The measurement instruments were the visual analogue scale (VAS) and the aberrant behaviour checklist (ABC). Statistically significant differences were found for placebo in 3 out of 6 children and for secretin in one child, using parental ratings only (VAS scores). Differences were small and lacked clinical significance, which was in accordance with the overall impression of the parents and teachers and visual inspection of graphs. Conclusion: In this placebo-controlled study, multiple doses of secretin did not produce any symptomatic improvement. [source]