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PubMed2000

Efficacy and tolerability of myrtol standardized in acute bronchitis. A multi-centre, randomised, double-blind, placebo-controlled parallel group clinical trial vs. cefuroxime and ambroxol.

UNLABELLED: Myrtol standardized (Gelomyrtol forte) is a phytotherapeutic extract (distillate) consisting mainly of three monoterpenes: (+)alpha-pinene, d-limonene and 1,8-cineole. OBJECTIVE: This study describes and compares the efficacy, safety and tolerability of a 2-week treatment with myrtol stand. (4 x 300 mg, day 1-14), cefuroxime (CAS 55268-75-2) (2 x 250 mg daily for day 1-6), ambroxol (CAS 18683-91-5) (3 x 30 mg for day 1-3, 2 x 30 mg for days 4-14) and matched placebo in acute bronchitis. PATIENTS: 676 male and female outpatients, aged > or = 18 years, with acute bronchitis of recent onset (within last 5 days), with an FEV1 > 75% of the normal EGKS-value and without evidence or suspicion of chronic pulmonary disease or any further confounding illness were included in the study. INTERVENTION: Patients were randomly assigned to a 2-week treatment course with either myrtol stand. (N = 170), cefuroxime (N = 171), ambroxol (N = 163) or placebo (N = 172) in a double-blind, placebo-matched, parallel-group fashion. Evaluations were at baseline (visit 1), after 1 and 2 weeks of treatment (visits 2 and 3) and at 2 weeks after conclusion of the treatments (visit 4). CRITERIA: Responder- and non-responder rates (primary), signs (abnormal auscultation), symptoms (daily diary data on nightly cough, coughing fits during the day, sputum consistence and general well-being; visit data on bronchial hyperreactivity and absence/presence of associated symptoms), FEV1, overall efficacy, absence of relapse, safety and tolerability (adverse events, laboratory screens, vital signs and physical examination). Criteria were evaluated for the intention-to-treat data-set (ITT) and the 'efficacy evaluable' sample (EAP), i.e. excluding patients with missing values (incl. discontinued non-responders and drop-outs for other reasons) at the time of assessment. RESULTS: The signs and symptoms of acute bronchitis regressed readily in all treatment groups, but regression was slower and less complete in the patients treated with placebo. In patients treated with placebo, the acute bronchitis was considered to have deteriorated to such an extent that discontinuation was indicated ('non-responder') in 36 patients (ITT: 20.9%, 95% CI: 15.1 to 27.8% and EAP: 21.3%, CI: 15.4 to 28.3%) after 1 week (visit 2) and in 19 further patients (ITT: 11.0%, CI: 6.8 to 16.7%; EAP: 14.8%, CI: 9.2 to 22.2%) after 1 further week (visit 3). In contrast, in the group of patients treated with myrtol stand. the non-responder rates at visits 2 and 3 were only 5.3% (ITT, CI: 2.4 to 9.8%; EAP: 5.4%, CI: 2.5 to 10.0%) and 1.2% (ITT, CI: 0.1 to 4.2%; EAP: 1.3%, CI: 0.2 to 4.7%); the responder rates at visit 2 were statistically significantly higher (p < 0.001) for myrtol stand. (ITT: 92.9%, CI: 88.0 to 96.3) compared to placebo (ITT: 77.3%, CI: 70.3 to 83.4), and similar to those for cefuroxime (ITT: 92.4%, CI: 87.4 to 95.9) and ambroxol (ITT: 89.6%, CI: 83.8 to 93.8%). The superiority of the active treatments vs. placebo with little difference among the treatments was confirmed for all further criteria of evaluation. There was no evidence of bronchoconstriction or relapse in any treatment group for the patients continuing treatment (i.e. for those who were not discontinued because of non-response). The treatments were safe and comparably well tolerated. CONCLUSION: Compared to placebo, treatment with myrtol stand. was well tolerated but evidently superior in terms of efficacy, resulting in a more rapid and more complete recovery; although well comparable with the other active treatments, myrtol stand. tended to be superior to cefuroxime and ambroxol for several ancillary criteria. Myrtol stand. is a well-evidenced alternative to antibiotics for acute bronchitis without specified infective agent, without the risk to promote the development of bacterial resistance.

Acute Disease↗
PubMed1999

Efficacy and tolerability of myrtol standardized in long-term treatment of chronic bronchitis. A double-blind, placebo-controlled study. Study Group Investigators.

This multicenter, placebo-controlled, double-blind, randomized parallel-group trial was conducted to investigate the efficacy and tolerability of myrtol standardized (MYS, Gelomyrtol forte, 3 x 300 mg) in the long-term treatment of patients with chronic bronchitis during the winter. 246 patients received the investigational treatments (MYS: 122, placebo: 124) for at least 1 month; 215 subjects (110 under MYS and 105 under placebo) were evaluable in terms of efficacy (exacerbation rate, the need for antibiotics, symptom scores and general well-being) for the protocol-defined 6 months of treatment. Statistically significantly (p < 0.01) more patients remained without acute exacerbation in the myrtol standardized group (72%) compared to the placebo group (53%). In the placebo group, there was an evident peak in the incidence of exacerbations during the third month of treatment, which was not observed in the active treatment group. In the MYS group, 51.6% of the patients with an acute exacerbation required antibiotics vs. 61.2% under placebo. 62.5% of the patients treated with antibiotics in the MYS group required them for < or = 7 days, whereas 76.7% of the patients in the placebo group treated with antibiotics for exacerbation needed antibiotics for > 7 days. Well-being (assessed in terms of general health and health impairment by cough and expectoration) was significantly better under treatment with MYS. The overall therapeutic efficacy evaluation scored higher for MYS. Therefore, it is concluded that long-term treatment with MYS is equally well tolerated as placebo but is clearly superior in efficacy in terms of protecting against acute exacerbations in patients with chronic bronchitis: it reduces the frequency and intensity of acute exacerbations, the need of antibiotics for them and the health impairment by cough and expectoration.

Aged↗
PubMed2004

Zotepine versus placebo in the treatment of schizophrenic patients with stable primary negative symptoms: a randomized double-blind multicenter trial.

BACKGROUND: In contrast to traditional antipsychotic medication, newer, the so called atypical antipsychotic drugs promise to reduce primary negative symptoms in both, acute and chronic schizophrenia and improve quality of life. Zotepine, a D (2)5HT (2A) antagonist, was compared to placebo in this clinical trial to address these issues. METHODS: In an adaptive, 8-week multicenter, double-blind, randomized, parallel group study, efficacy and tolerability as well as influence on quality of life of zotepine and placebo were compared in 80 schizophrenic patients (53 % males, age 41 +/- 11 years) who experienced stable primary negative symptoms. Efficacy was assessed using the PANSS (primary outcome criterion: PANSS negative score), CGI, and MADRS; safety was controlled by EPS (Simpson-Angus Scale), TDRS and adverse events. Quality of life was evaluated with the SF-36 health questionnaire. RESULTS: After eight weeks of treatment with an average dose of 131 +/- 49 mg/day of zotepine, no superior efficacy of zotepine compared to placebo with respect to the PANSS subscale "negative symptoms could be demonstrated. Although patients receiving zotepine showed a pronounced reduction (per protocol set: -7.8 +/- 5.8) during treatment, it was not statistically different from a marked placebo response (-6.5 +/- 5.8). Similar small but not significant differences between zotepine and placebo were found in other subscales of the PANSS, the CGI and the MADRS. With regards to the quality of life assessment, patients under zotepine showed better results in the physical component scale and psychological well-being scale. In general, zotepine was well tolerated and there was no excess of extrapyramidal symptoms compared to placebo. CONCLUSIONS: Zotepine was not superior to placebo in reducing the severity of stable primary negative symptoms in schizophrenic patients in this trial. The main reasons for this finding were a high placebo response in a selected population, a probably too low dose of zotepine, and a short study period. However, several findings show clinical benefit of zotepine therapy in efficacy and quality of life.

Adolescent↗
PubMed1998

Interferon gamma-1b compared with placebo in metastatic renal-cell carcinoma. Canadian Urologic Oncology Group.

BACKGROUND: Most trials of immunomodulators in metastatic renal-cell carcinoma have been uncontrolled and subject to selection bias. The objective of this blinded, placebo-controlled study was to compare overall response rates, time to disease progression, and survival of patients with metastatic renal-cell carcinoma treated with recombinant human interferon gamma-1b or placebo. METHODS: Patients with biopsy-proved metastatic renal-cell carcinoma were randomly assigned to receive interferon gamma-1b (60 microg per square meter of body-surface area subcutaneously once weekly) or placebo. The primary tumor had been treated by nephrectomy or angioinfarction at least three weeks previously. Patients were evaluated for radiologic evidence of progression, and all responses were independently reviewed by a committee that was unaware of the treatment. RESULTS: A total of 197 patients with metastatic renal-cell carcinoma were enrolled at 17 centers in Canada. One hundred eighty-one patients could be evaluated; of these, 91 were assigned to receive interferon gamma-1b and 90 were given placebo. The groups were well balanced in terms of prognostic factors. Two thirds of all patients had Karnofsky scores of 90 or 100, and more than half had two or more metastatic sites. Grade I and II toxicity, mostly chills, fever, asthenia, or headaches, was reported in 91 percent and 61 percent, respectively, of the patients in the interferon group, as compared with 76 percent and 63 percent in the placebo group. Life-threatening drug-related events were rare, occurring in 1 percent of patients in the interferon group. No significant differences between groups were observed in overall response rates, time to disease progression, or survival. The overall response rate was 4.4 percent (3.3 percent complete response and 1.1 percent partial response) in the interferon group and 6.6 percent (3.3 percent complete response and 3.3 percent partial response) in the placebo group (P=0.54), with a rate of durable complete response of 1 percent in both groups. The median time to disease progression was 1.9 months in both groups (P=0.49), and there was no significant difference in median survival (12.2 months with interferon vs. 15.7 months with placebo, P=0.52). CONCLUSIONS: No difference in outcome was observed in patients with metastatic renal-cell carcinoma who were treated with interferon gamma-1b as compared with placebo. These results emphasize the necessity of testing the efficacy of immunomodulators in randomized studies.

Adjuvants, Immunologic↗
PubMed2002

Effect of desloratadine versus placebo on nasal airflow and subjective measures of nasal obstruction in subjects with grass pollen-induced allergic rhinitis in an allergen-exposure unit.

BACKGROUND: Unlike many antihistamines, desloratadine can reduce nasal congestion in patients with seasonal allergic rhinitis (SAR). OBJECTIVE: We compared the effects of 5 mg of desloratadine and placebo on nasal airflow and SAR symptoms, including nasal congestion, in response to grass pollen in an allergen-exposure unit. METHODS: In a randomized, double-blind, placebo-controlled, crossover trial, 47 subjects with histories of SAR received desloratadine or placebo every morning for 7 days and, after a 10-day washout period, were crossed over to the other treatment arm for 7 days. Subjects underwent a 6-hour allergen exposure on day 7 of each treatment period. Nasal airflow and nasal secretion weights were measured before and every 30 minutes during allergen exposure; SAR symptoms (including nasal congestion) were scored before exposure and every 15 minutes thereafter. RESULTS: Nasal obstruction, as measured by nasal airflow, was less severe with desloratadine than with placebo (P <.02). Individual and combined SAR symptom severity scores, including nasal congestion and sneezing, were significantly lower with desloratadine than with placebo (all P < or =.003). Within 30 minutes of allergen exposure, less severely decreased nasal airflow (P <.02), less nasal secretions (P <.001), and less severe symptoms, including nasal congestion (P <.002), rhinorrhea, and sneezing, occurred with desloratadine compared with placebo, and this continued throughout (0-6 hours) allergen exposure. Desloratadine was well tolerated, with an adverse event profile similar to that of placebo. CONCLUSION: In subjects with allergen-induced SAR symptoms, desloratadine significantly reduced the severity of nasal obstruction and accompanying complaints of nasal congestion and other SAR symptoms compared with the effects of placebo.

Adult↗
PubMed2002

Duloxetine versus placebo in the treatment of stress urinary incontinence.

OBJECTIVE: The purpose of this study was to assess the efficacy and safety of duloxetine, a selective inhibitor of serotonin and norepinephrine reuptake, in the treatment of stress urinary incontinence. STUDY DESIGN: A double-blind, randomized, placebo-controlled study was conducted in 553 women aged 18 to 65 years with a predominant symptom of stress urinary incontinence. Subjects were randomized to placebo (n = 138 women) or duloxetine at one of three doses (20 mg/d, n = 138 women; 40 mg/d, n = 137 women; or 80 mg/d, n = 140 women). Outcome variables that were assessed after 12 weeks of treatment included incontinence episode frequency recorded in a real-time diary and answers provided to the Patient Global Impression of Improvement scale and the Incontinence Quality of Life questionnaire. RESULTS: Duloxetine was associated with significant and dose-dependent decreases in incontinence episode frequency that paralleled improvements that were observed in the Patient Global Impression of Improvement scale and the Incontinence Quality of Life questionnaire. The median incontinence episode frequency decrease with the use of the pooled diary analysis with placebo was 41% compared with 54% for duloxetine 20 mg per day (P =.06), 59% for duloxetine 40 mg per day (P =.002), and 64% for duloxetine 80 mg per day (P <.001). One half of the subjects at the 80 mg per day dose had a > or = 64% reduction in incontinence episode frequency (P <.001 vs placebo); 67% had > or = 50% reduction (P =.001 vs placebo). These improvements were observed despite significant concurrent dose-dependent increases in the average voiding interval in the duloxetine groups compared with the placebo group. Similar statistically significant improvements were demonstrated in a subgroup of 163 subjects who had more severe stress urinary incontinence (> or = 14 incontinence episode frequency per week; 49%-64% reduction in incontinence episode frequency in the duloxetine groups compared with 30% in the placebo group). Discontinuation rates for adverse events were 5% for placebo and 9%, 12%, and 15% for duloxetine 20, 40, and 80 mg per day, respectively (P =.04). Nausea was the most common symptom that led to discontinuation. None of the adverse events that were reported were considered to be clinically severe. CONCLUSION: This trial provides evidence for the efficacy and safety of duloxetine as a pharmacologic agent for the treatment of stress urinary incontinence.

Analysis of Variance↗
PubMed2004

A double-blind, placebo-controlled, randomized study to evaluate the efficacy, safety and tolerability of tegaserod in patients with irritable bowel syndrome.

BACKGROUND: Tegaserod has been shown to be an effective therapy for the multiple symptoms of irritable bowel syndrome (IBS) in Western and Asia-Pacific populations. This study evaluated the efficacy, safety and tolerability of tegaserod versus placebo in patients with IBS. METHODS: Patients with IBS (excluding those whose primary bowel symptom was diarrhoea) were randomized to receive either tegaserod 6 mg b.i.d. (n = 327) or placebo (n = 320) for a 12-week double-blind treatment period. The primary efficacy variable (over weeks 1 to 4) was the response to the question: 'Over the past week do you consider that you have had satisfactory relief from your IBS symptoms?' Secondary efficacy variables assessed overall satisfactory relief over 12 weeks and the individual IBS symptoms. RESULTS: Overall satisfactory relief was greater in the tegaserod group than in the placebo group. Over weeks I to 4, the odds ratio was 1.54, that is, the odds of satisfactory relief were 54% higher in the tegaserod group than in the placebo group (95% confidence interval for odds ratio (CI) (1.14, 2.08), P = 0.0049). Over weeks 1 to 12, the odds ratio was 1.78, that is, the odds of satisfactory relief were 78% higher in the tegaserod group than in the placebo group (95% CI (1.35, 2.34), P < 0.0001). A statistically significant therapeutic gain over placebo was observed for the majority of weeks from week 1 to week 12 (except weeks I and 4), with a mean therapeutic gain of 7.3 and 10.6 percentage points over weeks 1-4 and weeks 1-12, respectively. Headache was the most commonly reported adverse event (8.0% tegaserod versus 4.7% placebo). Diarrhoea was reported by 9.2% of patients on tegaserod (1.3% on placebo) and led to discontinuation in 2.8% of tegaserod patients. CONCLUSION: Tegaserod 6 mg b.i.d. is an effective, safe and well-tolerated treatment in patients suffering from IBS without diarrhoea as primary bowel symptom.

Adolescent↗
PubMed2006

Efficacy of spirulina extract plus zinc in patients of chronic arsenic poisoning: a randomized placebo-controlled study.

BACKGROUND: Millions of people in Bangladesh, India, Taiwan, and Chile are consuming high concentration of arsenic through drinking water, and thousands of them have already developed chronic arsenic poisoning. There is no specific treatment. Some authors suggest the use of vitamins and minerals for more than 6 months. The present placebo-controlled double-blind study was conducted to evaluate effectiveness of spirulina extract plus zinc in the treatment of chronic arsenic poisoning. METHODS: Forty-one patients of chronic arsenic poisoning were randomly treated orally by either placebo (17 patients) or spirulina extract (250 mg) plus zinc (2 mg) (24 patients) twice daily for 16 weeks. Each patient was supplied with arsenic-safe drinking water by installing a locally made water filter at household level. Effectiveness of spirulina extract plus zinc was evaluated by comparing changes in skin manifestations (clinical scores), arsenic contents in urine and hair, between the placebo- and spirulina extract plus zinc-treated groups. RESULTS: The concentrations of total arsenic in water (without filtration) of placebo- and spirulina extract plus zinc-treated groups were 150.1 +/- 18.3 and 161.7 +/- 23.9 microg/l, respectively. Intake of these high concentrations of arsenic lead to increased excretion of arsenic in urine (72.1 +/- 14.5 microg/l in placebo-treated group and 78.4 +/- 19.1 microg/l in spirulina plus zinc-treated group). After 2 weeks of using filtered water, there were significant reduction of both arsenic intake through water and urinary arsenic excretion (8.3 +/- 3.6 microg/l and 18.4 +/- 7.3 microg/l in placebo group; 9.7 +/- 5.4 microg/l and 21.6 +/- 5.8 microg/l) in spirulina extract plus zinc-treated group. There was a sharp increase in urinary excretion of arsenic (138 +/- 43.6 microg/l) at 4 weeks following spirulina plus zinc administration and the effect was continued for another 2 weeks. Spirulina extract plus zinc removed 47.1% arsenic from scalp hair. Spirulina extract had no major adverse effect that required physician's attention. The clinical scores (median) for melanosis before and after treatment with placebo was not statistically significant (p > 0.05), whereas in spirulina extract plus zinc-treated group it was statistically significant (p < 0.01). In cases of keratosis, the median clinical scores before and after treatment was not statistically significant (p > 0.05) in placebo-treated group. In spirulina extract plus zinc-treated group, the clinical scores for keratosis before and after treatment was statistically significant (p < 0.05). CONCLUSIONS: Results show that spirulina extract (250 mg) plus zinc (2 mg) twice daily for 16 weeks may be useful for the treatment of chronic arsenic poisoning with melanosis and keratosis.

Adolescent↗
PubMed2001

Can homeopathically prepared mercury cause symptoms in healthy volunteers? A randomized, double-blind placebo-controlled trial.

OBJECTIVE: To pilot a method for determining whether homeopathically prepared mercury causes more symptoms (a "drug proving") in healthy volunteers than placebo. METHODS: One hundred and eighteen (118) healthy volunteers ages 18 to 65 were recruited by local advertising. Subjects unfamiliar with homeopathy undertook a 1-week single-blind placebo run-in, a 1-week of double-blind, randomized treatment on either homeopathically prepared mercury 12C or placebo, and a third week of placebo run-out. Each day, symptoms were recorded on a checklist that included both true mercury symptoms and symptoms not expected to be caused by mercury (false symptoms). Additional symptoms were assessed by open reporting. Outcome was assessed by calculating a score for each day as the number of true symptoms minus the number of false symptoms. The mean score during placebo was then subtracted from the mean score for weeks two and three of the trial. RESULTS: Fourteen (14) subjects dropped out during placebo run-in. The remaining 104 completed the trial. Baseline comparability was good. Mean difference score was -0.125 (SD 3.47) for mercury and -0.221 (SD 3.01) for placebo (p > 0.2). No significant differences between groups were found for the number of subjects meeting predefined criteria for a drug-proving reaction. CONCLUSION: This pilot study failed to find evidence that mercury 12C causes significantly more symptoms in healthy volunteers than placebo. Questionnaires with a limited number of gross symptoms do not seem to be an appropriate methodological technique in drug proving research. If drug-proving phenomena exist, they appear to be rare.

Adolescent↗
PubMed2004

Individual differences in response to randomly assigned active individualized homeopathic and placebo treatment in fibromyalgia: implications of a double-blinded optional crossover design.

OBJECTIVE: To assess individual difference characteristics of subgroups of patients with fibromyalgia (FM) patients with respect to the decision to stay in or switch from randomly-assigned verum or placebo treatment during an optional crossover phase of a double-blinded homeopathy study. DESIGN: Double-blinded, randomized, placebo-controlled, optional crossover clinical trial. PARTICIPANTS: Fifty-three (53) community-recruited patients with FM entered the optional crossover phase. INTERVENTION: Two homeopaths jointly selected an individualized homeopathic remedy for all patients. The pharmacy dispensed either verum LM remedy or indistinguishable placebo in accord with randomized assignment for 4 months and the patient's optional crossover decision for an additional 2 months. OUTCOME MEASURES: Patients completed a battery of baseline state/trait questionnaires, including mood, childhood neglect and abuse, and trait absorption. They rated global health (whole person-centered) and tender point pain on physical examination (disease-specific) at baseline, 3 months, and 6 months. RESULTS: Rates of optional crossover from verum to placebo or placebo to verum were comparable (p = 0.6; 31%, and 41%, respectively). The switch subgroups had greater baseline psychologic issues (emotional neglect in placebo-switch; depression and anger in verum-switch). The verum-stay subgroup scored highest on treatment helpfulness and included all six exceptional responders who fell, prior to crossover, into the top terciles for improvement in both global health and pain. Patients staying in their randomly assigned groups, active or placebo (n = 34), scored significantly higher in trait absorption than did those who switched groups (n = 19). CONCLUSION: Individual difference factors may predict better and poorer responders with FM to specific and nonspecific effects of homeopathic and placebo treatment.

Adult↗
PubMed1993

Multicenter, randomized, placebo-controlled study of ditiocarb (Imuthiol) in human immunodeficiency virus-infected asymptomatic and minimally symptomatic patients. The HIV87 Study Group.

Ditiocarb sodium has been reported to reduce the progression of human immunodeficiency virus (HIV) infection. To confirm this therapeutic activity and to evaluate the effect of ditiocarb sodium in the early stages of HIV infection, we conducted a randomized, double-blind, placebo-controlled trial in asymptomatic or minimally symptomatic adults with HIV infection. Patients were followed during a 24 mo period, with a clinical and laboratory evaluation every 4 mo. Of 1333 patients who continued therapy after day 1, 669 were randomized to ditiocarb and 664 to placebo. The two treatment groups were comparable at entry, except for the CD4+ cell count, which was lower in the ditiocarb (median 416/mm3) than in the placebo group (median 458/mm3). Acquired immunodeficiency syndrome (AIDS) developed in 106 patients in the ditiocarb group as compared with 68 in the placebo group; 285 patients progressed to AIDS-related complex (157 ditiocarb, 128 placebo); 55 patients died (34 ditiocarb; 21 placebo). The risk of progression to AIDS, after adjustment for baseline CD4+ cell count, was significantly higher in the ditiocarb than in the placebo group (adjusted relative risk = 1.41; p = 0.027). A decrease in CD4+ cell counts was observed, with no significant difference between the ditiocarb and the placebo group. A positive effect of ditiocarb given in the condition of this study can be excluded. Although previous studies have shown opposite results, this study suggests that the use of ditiocarb in HIV-infected patients should be discontinued.

AIDS-Related Complex↗
PubMed1997

Randomized placebo-controlled trial of brisk walking in the prevention of postmenopausal osteoporosis.

OBJECTIVE: to evaluate the effects of brisk walking on bone mineral density in women who had suffered an upper limb fracture. DESIGN: randomized placebo-controlled trial. Assessments of bone mineral density were made before and at 1 and 2 years after intervention. Standardized and validated measures of physical capacity, self-rated health status and falls were used. SETTING: district general hospital outpatient department. SUBJECTS: 165 women drawn from local accident and emergency departments with a history of fracture of an upper limb in the previous 2 years. Women were randomly allocated to intervention (self-paced brisk walking) or placebo (upper limb exercises) groups. INTERVENTION: both groups were seen at 3-monthly intervals to assess progress, measure physical capacity and maintain enthusiasm. The brisk-walking group were instructed to progressively increase the amount and speed of walking in a manner that suited them. The upper limb exercise placebo group were asked to carry out a series of exercises designed to improve flexibility and fine hand movements, appropriate for a past history of upper limb fracture. RESULTS: drop-outs from both intervention and placebo groups were substantial (41%), although there were no significant differences in bone mineral density, physical capacity or health status between drop-outs and participants. At 2 years, among those completing the trial, bone mineral density at the femoral neck had fallen in the placebo group to a greater extent than in the brisk-walking group [mean net difference between intervention and placebo groups 0.019 g/cm2, 95% confidence interval (CI) -0.0026 to +0.041 g/cm2, P = 0.056]. Lumbar spine bone mineral density had increased to a similar extent (+0.017 g/cm2) in both groups. The cumulative risk of falls was higher in the brisk-walking group (excess risk of 15 per 100 person-years, 95% CI 1.4-29 per 100 person-years, P < 0.05). There were no significant differences in clinical or spinal x-ray fracture risk or self-rated health status between intervention and placebo groups. CONCLUSION: the promotion of exercise through brisk-walking advice given by nursing staff may have a small, but clinically important, impact on bone mineral density but is associated with an increased risk of falls. Self-paced brisk walking is difficult to evaluate in randomized controlled trials because of drop-outs, placebo group exercise, limited compliance and lack of standardization of the duration and intensity of walking. Further work is needed to evaluate the best means of safely achieving increased activity levels in different groups, such as older women and those at high risk of fractures.

Accidental Falls↗
PubMed1993

Influence of angiotensin converting enzyme inhibition on exercise performance and clinical symptoms in chronic heart failure: a multicentre, double-blind, placebo-controlled trial.

One hundred and seven patients with chronic heart failure (NYHA class II to IV) stabilized on digitalis and/or diuretics, recruited from 11 centres were randomized into a double-blind, placebo-controlled study to assess the effect of 12 weeks of cilazapril therapy on exercise tolerance and clinical status. Thirty-five patients were randomized to placebo and 72 to cilazapril at a starting dose of 1 mg daily; titration to cilazapril 2.5 mg at week 4 and 5 mg at week 8 (or matching placebo) was carried out in patients who did not improve clinically. Demographic characteristics, including exercise test duration increased from 402 s (+/- 17 SEM) at baseline to 462 s (+/- 19 SEM) at week 12 for the cilazapril group (+15%) and from 405 s (+/- 23 SEM) at baseline to 408 s (+/- 30 SEM) at week 12 in patients on placebo (+1%) (P < 0.001). In the placebo group, patients able to exercise for more than 6 min at baseline showed an increase in exercise duration at week 12 while those able to exercise for up to 6 min at baseline showed a decrease (P = ns). In contrast, cilazapril-treated patients showed an increase in exercise tolerance regardless of baseline exercise test duration; patients with the most impaired exercise tolerance at baseline showed a greater improvement than patients with mildly impaired baseline exercise tolerance (P < 0.05 vs placebo). NYHA class improved by at least one grade in 51% of the cilazapril group vs 32% in the placebo group (P = ns). At the end of the trial, 15% of the patients were non-responders on cilazapril vs 41% on placebo (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2001

Effectiveness of nystatin in polysymptomatic patients. A randomized, double-blind trial with nystatin versus placebo in general practice.

BACKGROUND: Antifungal therapy has been claimed to be effective in polysymptomatic patients with diffuse symptoms from multiple body systems and even well defined diseases, traditionally not related to fungi. Hypersensitivity to fungus proteins and mycotoxins has been proposed as the cause. METHODS: We conducted a 4-week randomized, double-blind, placebo-controlled study in 116 individuals selected by a 7-item questionnaire to determine whether the antifungal agent nystatin given orally was superior to placebo. At the onset of the study, the patients were free to select either their regular diet or a sugar- and yeast-free diet, which resulted in four different subgroups: nystatin + diet (ND); placebo + diet (PD); nystatin (N); and placebo (P). RESULTS: Nystatin was significantly better than placebo in reduction of the overall symptom score (P < 0.003). In six of the 45 individually recorded symptoms, the improvement was significant (P < 0.01). All three active treatment groups reduced their overall symptom scores significantly (P < 0.0001), while the placebo regimen had no effect (P = 0.83). The benefit of diet was significant within both the nystatin (ND > N) and the placebo groups (PD > P). CONCLUSIONS: Nystatin is superior to placebo in reducing localized and systemic symptoms in individuals with presumed fungus hypersensitivity as selected by a 7-item questionnaire. This superiority is probably enhanced even further by a sugar- and yeast-free diet.

Adult↗
PubMed1995

Early single dose therapy with ofloxacin for empirical treatment of acute gastroenteritis: a randomised, placebo-controlled double-blind clinical trial.

This study is a double-blind, placebo-controlled, randomised clinical trial to evaluate the clinical and microbiological efficacy and safety of single dose ofloxacin for acute diarrhoea. Eligible patients were 16 years of age or older with a history of acute diarrhoea lasting no more than 48 h; 117 patients were randomised and 97.4% (114/117) were evaluable for efficacy. Of these, 58% were suspected to have ingested contaminated foods. Enteric pathogens were isolated in 61.5% of the patients, Salmonella enteritidis being reported in 87.5%. The patients received either a single 400 mg dose of ofloxacin, or placebo. The average duration of diarrhoea was 2.56 +/- 2.21 days in the ofloxacin group and 3.41 +/- 2.5 in the placebo group (P = 0.117). The average duration of fever was 0.63 +/- 0.95 days in the ofloxacin group and 1.05 +/- 0.96 in the placebo group (P = 0.02). Symptoms remained unchanged for more than 48 h in only 7% of the patients who received ofloxacin, compared with 12% in the placebo group (P = 0.485). Only 32% of patients in the ofloxacin group remained culture positive after 48 h compared with 59% in the placebo group (P = 0.0018). These represent a relative risk reduction (RRR) for stool clearance of 45.5% and absolute risk reduction (ARR) of 27% (95% Cl, 8-44.7), with a number of patients needed to treat (NNT) of 3.7 (95%, 2.7-11.3). After 15 days, 23.3% of patients in the ofloxacin group had a positive culture compared with 28.9% in the placebo (P = 0.63). This represents an RRR of 19%, an ARR of 5.6% and a NNT of 17.8. Adverse events in the ofloxacin group were observed in only one patient who reported headache and in one patient in the placebo group who developed a rash. In summary, empirical treatment with a single dose of ofloxacin in acute diarrhoea did not reduce the intensity or duration of symptoms (except possibly length of fever). It was notable however that stool cultures became negative for S. enteritidis by 48 h, with no relapse after 2 weeks of follow-up.

Acute Disease↗
PubMed1998

A 25-week placebo-controlled study of eptastigmine in patients with Alzheimer disease.

The efficacy and safety of eptastigmine in patients with probable Alzheimer disease was evaluated in a double-blind, placebo-controlled, parallel group study. Patients with mild to moderate dementia were randomly assigned to placebo, eptastigmine 10 mg three times a day (t.i.d.), or eptastigmine 15 mg t.i.d. over 25 weeks. The Alzheimer Disease Assessment Cognitive Subscale (ADAS-Cog) and the Clinician's Interview-Based Impression of Change Plus (CIBIC-Plus) were the primary outcome measures for efficacy. Twenty-six centers recruited 320 patients: 106 on placebo, 105 on eptastigmine 10 mg t.i.d., and 109 on eptastigmine 15 mg t.i.d. Six patients on placebo (6%), 18 patients on eptastigmine 10 mg t.i.d. (17%), and 10 patients on eptastigmine 15 mg t.i.d. (9%) discontinued study treatment. The intent-to-treat analysis on 315 patients showed a statistically significant (p=0.047) difference of 2.0 points on ADAS-Cog between the placebo and the eptastigmine 15 mg t.i.d. group at the end of treatment. Patients in the 10 mg t.i.d. group performed better than did placebo-treated patients on the Spontaneous Behavior Interview (SBI) total scores (p=0.015) and on the Activities of Daily Living (ADL, p=0.043) and Behavioral Problems (BP, p=0.028) subscales. The differences in favor of the eptastigmine groups on the CIBIC-Plus did not reach statistical significance. In a post hoc subgroup analysis by staging, the effect size of eptastigmine was found to be greater in the most severely impaired patients (Global Deterioration Scale rating of 4 and 5 at screening) reaching statistical significance in both ADAS-Cog (p=0.007) and CIBIC-Plus (p=0.038). In this patient subgroup (n=222), there was also a significant effect of eptastigmine on SBI (p=0.019). The drug was generally well tolerated, with 8% of patients withdrawing due to adverse events versus 5% on placebo. Adverse events were recorded in 35 patients (33%) on placebo compared with 41 (39%) on eptastigmine 10 mg t.i.d. and 38 (35%) on eptastigmine 15 mg t.i.d. This study shows that eptastigmine doses up to 15 mg t.i.d. for 25 weeks are well tolerated. The drug positively affects cognitive performance of Alzheimer patients. This effect appears greater in more severely impaired patients and also impacts on their behavioral performance.

Aged↗
PubMed1996

Liposomal prostaglandin E1 in acute respiratory distress syndrome: a placebo-controlled, randomized, double-blind, multicenter clinical trial.

OBJECTIVE: To evaluate the safety and efficacy of liposomal prostaglandin E1 (TLC C-53) in the treatment of patients with the acute respiratory distress syndrome (ARDS). DESIGN: Randomized, prospective, multicenter, double-blind, placebo-controlled, phase II clinical trial. SETTING: Eight community and university-affiliated hospitals in the United States. PATIENTS: Twenty-five patients with ARDS. INTERVENTIONS: Patients were prospectively randomized in an unbalanced ratio within each site to receive either TLC C-53 (n = 17) or placebo (n = 8). Study drug was infused intravenously over 60 mins every 6 hrs for a 7-day period, starting at a dose of 0.15 micrograms/kg/hr. The dose was increased every 12 hrs until the maximal dose (3.6 micrograms/kg/hr) was attained, intolerance to further increases developed, or invasive monitoring was discontinued. Patients received standard, aggressive, medical/surgical care throughout the trial. MEASUREMENTS AND MAIN RESULTS: Outcome measurements were Pao2/FI0(2), dynamic pulmonary compliance, ventilator dependence on day 8, and 28-day all-cause mortality rate. At baseline, the distribution of variables describing Lung Injury Scores, Acute Physiology and Chronic Health Evaluation II scores, Pao2/FI0(2), pulmonary compliance, and time from onset of ARDS to first dose of study drug was similar between patients in the TLC C-53 and placebo treatment groups. On day 8, all eight patients given placebo required mechanical ventilation, while eight of 17 patients given TLC C-53 were healthy enough to be removed from the ventilator (p = .03). Improvement in PaO2/FIO2 during the initial 8-day study period was greater in patients receiving TLC C-53. This trend achieved statistical significance on day 3, when the increase in PaO2/FIO2 from baseline was 82.5 +/- 14.6 in the TLC C-53 group compared with 28.3 +/- 22.1 in the placebo group (p = .05). By day 8, lung compliance also increased from baseline significantly more in TLC C-53 patients than in placebo patients (5.7 +/- 1.7 vs -1.5 +/- 1.8 mL/cm H2O; p = .01). The 28-day mortality rate was 6% (1/17 patients) in the TLC C-53 group and 25% (2/8 patients) in the placebo group (p = .23). Drug-related adverse events were reported in 82% of the patients receiving TLC C-53 compared with 38% of the placebo group, with half of the adverse events in the TLC C-53 group being localized infusion site irritation. TLC C-53 was hemodynamically well tolerated, with transient hypotension occurring in three patients. CONCLUSIONS: In patients with ARDS, TLC C-53 was associated with improved oxygenation, increased lung compliance, and decreased ventilator dependency.

Adult↗
PubMed1999

Efficacy of recombinant human erythropoietin in the critically ill patient: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To determine whether the administration of recombinant human erythropoietin (rHuEPO) to critically ill patients in the intensive care unit (ICU) would reduce the number of red blood cell (RBC) transfusions required. DESIGN: A prospective, randomized, double-blind, placebo-controlled, multicenter trial. SETTING: ICUs at three academic tertiary care medical centers. PATIENTS: A total of 160 patients who were admitted to the ICU and met the eligibility criteria were enrolled in the study (80 into the rHuEPO group; 80 into the placebo group). INTERVENTIONS: Patients were randomized to receive either rHuEPO or placebo. The study drug (300 units/kg of rHuEPO or placebo) was administered by subcutaneous injection beginning ICU day 3 and continuing daily for a total of 5 days (until ICU day 7). The subsequent dosing schedule was every other day to achieve a hematocrit (Hct) concentration of >38%. The study drug was given for a minimum of 2 wks or until ICU discharge (for subjects with ICU lengths of stay >2 wks) up to a total of 6 wks (42 days) postrandomization. MEASUREMENTS AND MAIN RESULTS: The cumulative number of units of RBCs transfused was significantly less in the rHuEPO group than in the placebo group (p<.002, Kolmogorov-Smirnov test). The rHuEPO group was transfused with a total of 166 units of RBCs vs. 305 units of RBCs transfused in the placebo group. The final Hct concentration of the rHuEPO patients was significantly greater than the final Hct concentration of placebo patients (35.1+/-5.6 vs. 31.6+/-4.1; p<.01, respectively). A total of 45% of patients in the rHuEPO group received a blood transfusion between days 8 and 42 or died before study day 42 compared with 55% of patients in the placebo group (relative risk, 0.8; 95% confidence interval, 0.6, 1.1). There were no significant differences between the two groups either in mortality or in the frequency of adverse events. CONCLUSIONS: The administration of rHuEPO to critically ill patients is effective in raising their Hct concentrations and in reducing the total number of units of RBCs they require.

Critical Illness↗