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Results for “Randomized trial”

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PubMed2005

Radiotherapy alone or combined with carbogen breathing for squamous cell carcinoma of the head and neck: a prospective, randomized trial.

BACKGROUND: The current study was performed to investigate the efficacy of carbogen (95% oxygen [O(2)] and 5% carbon dioxide [CO(2)]) breathing during definitive radiotherapy (RT) to enhance local control. METHODS: Between November 1996 and November 2002, 101 patients with previously untreated T2 to T4 squamous cell carcinomas of the oropharynx, larynx, and hypopharynx were entered onto a prospective trial and randomized to receive definitive hyperfractionated RT alone or combined with carbogen breathing. Patients were stratified according to T classification and primary tumor site. Follow-up ranged from 1-91 months (median, 38 months). All living patients had follow-up for more than 2 years. Outcomes analyses were performed according to intent to treat. RESULTS: Definitive RT alone was completed as planned in 50 of 51 patients (98%); 49 of the 50 patients (98%) who were randomized to receive carbogen breathing were able to complete the RT as planned. Three patients randomized to receive carbogen breathing declined carbogen. The 5-year outcomes after RT alone or combined with carbogen were as follows: local control, 83% versus 88% (P = 0.5155); locoregional control, 81% versus 83% (P = 0.7174); distant metastasis-free survival, 82% versus 86% (P = 0.5184); cause-specific survival, 73% versus 77% (P = 0.5866); and absolute survival, 53% versus 58% (P = 0.4856). CONCLUSIONS: The addition of carbogen breathing to definitive RT did not appear to improve the likelihood of local control significantly. However, because of the limited size of the current study, the authors cannot definitively conclude that carbogen breathing is ineffective.

Carbon Dioxide↗

PubMed2004

A double-blind randomized trial of 5% ascorbic acid vs. 4% hydroquinone in melasma.

BACKGROUND: Melasma is an acquired treatment-resistant hyperpigmentation of the skin. METHODS: Sixteen women with idiopathic melasma were included in our trial. After randomization by another clinician, they were instructed to use, at night, 5% ascorbic acid cream on one side of the face and 4% hydroquinone cream on the other side, for 16 weeks. Sunscreen was applied daily throughout the period of observation. They were evaluated every month by colorimetry, digital photography, and regular color slides. Subjective evaluation by each patient was also taken into account. RESULTS: The best subjective improvement was observed on the hydroquinone side with 93% good and excellent results, compared with 62.5% on the ascorbic acid side (P < 0.05); however, colorimetric measures showed no statistical differences. Side-effects were present in 68.7% (11/16) with hydroquinone vs. 6.2% (1/16) with ascorbic acid. CONCLUSION: Although hydroquinone showed a better response, ascorbic acid may play a role in the therapy of melasma as it is almost devoid of side-effects; it could be used alone or in combination therapy.

Administration, Topical↗

PubMed1995

Double-blind, randomized trial of roxatidine 150 mg in the early evening versus bedtime administration in the short-term treatment of duodenal ulcer.

AIM: To compare the efficacy and tolerability of early evening (19.00-21.00 hours) vs. bedtime (22.00-00.00 hours) oral administration of roxatidine 150 mg in the short-term treatment of active duodenal ulcer. METHODS: The trial was randomized, double-blind and double-dummy, with parallel groups. A total of 276 patients were recruited and randomly assigned either to roxatidine in the early evening (n = 139) or roxatidine at bedtime (n = 137). RESULTS: After 4 weeks, 78% of patients receiving roxatidine in the early evening and 74% of those treated at bedtime had achieved complete healing, as determined by per-protocol analysis. With intention-to-treat analysis the healing rates were 70.5% and 70.8%, respectively. After 8 weeks the healing rates in the early evening and bedtime treatment groups were 92% and 95% (per-protocol analysis) and 78% and 84% (intention-to-treat analysis). Both treatments proved effective in reducing the frequency and severity of daytime and nocturnal epigastric pain, as well as other ulcer-related symptoms. CONCLUSIONS: This study confirmed the healing and analgesic properties of roxatidine in duodenal ulcer disease. Early evening or bedtime dosing with roxatidine 150 mg resulted in similar 4- to 8-week rates of duodenal ulcer healing.

Administration, Oral↗

PubMed2002

Raloxifene and cardiovascular events in osteoporotic postmenopausal women: four-year results from the MORE (Multiple Outcomes of Raloxifene Evaluation) randomized trial.

CONTEXT: Raloxifene, a selective estrogen receptor modulator, improves cardiovascular risk factors, but its effect on cardiovascular events is unknown. OBJECTIVE: To determine the effect of raloxifene on cardiovascular events in osteoporotic postmenopausal women. DESIGN: Secondary analysis of data from the Multiple Outcomes of Raloxifene Evaluation trial, a randomized, double-blind, placebo-controlled trial conducted between November 1994 and September 1999. SETTING: Outpatient and community settings at 180 sites in 25 countries. PARTICIPANTS: A total of 7705 osteoporotic postmenopausal women (mean age, 67 years). INTERVENTION: Patients were randomly assigned to receive raloxifene, 60 mg/d (n = 2557), or 120 mg/d (n = 2572), or placebo (n = 2576) for 4 years. MAIN OUTCOME MEASURES: Cardiovascular events, including coronary events (myocardial infarction, unstable angina, or coronary ischemia) and cerebrovascular events (stroke or transient ischemic attack), collected as safety end points and subsequently adjudicated by a cardiologist blinded to therapy. Cardiovascular risk at study entry was determined by the presence of multiple cardiovascular risk factors or prior coronary events or revascularization procedure. RESULTS: In the overall cohort, there were no significant differences between treatment groups in the number of combined coronary and cerebrovascular events: 96 (3.7%) with placebo, 82 (3.2%) with 60 mg/d of raloxifene, and 94 (3.7%) with 120 mg/d of raloxifene. Relative risks (RRs) were 0.86 (95% confidence interval [CI], 0.64-1.15) and 0.98 (95% CI, 0.74-1.30) for 60 mg/d and 120 mg/d of raloxifene, respectively. Similar results were obtained when coronary and cerebrovascular events were analyzed separately. Among the subset of 1035 women with increased cardiovascular risk at baseline, those assigned to raloxifene had a significantly lower risk of cardiovascular events compared with placebo (RR, 0.60; 95% CI, 0.38-0.95 for both raloxifene groups). The number of cardiovascular events during the first year was not significantly different across groups in the overall cohort (P =.94), or among women at increased cardiovascular risk (P =.86) or with evidence of established coronary heart disease (P =.60). CONCLUSIONS: Raloxifene therapy for 4 years did not significantly affect the risk of cardiovascular events in the overall cohort but did significantly reduce the risk of cardiovascular events in the subset of women with increased cardiovascular risk. There was no evidence that raloxifene caused an early increase in risk of cardiovascular events. Before raloxifene is used for prevention of cardiovascular events, these findings require confirmation in trials with evaluation of cardiovascular outcomes as the primary objective.

Aged↗

PubMed1993

Extracorporeal shock wave lithotripsy in situ or after push-up for upper ureteral calculi: a prospective randomized trial.

A total of 110 patients with upper ureteral calculi was admitted to a prospective trial and randomly allocated to 2 groups: 1 group treated with in situ extracorporeal shock wave lithotripsy (ESWL) and 1 group treated with ureteral manipulation before ESWL. All patients had solitary upper ureteral calculi without urinary infection. The stones had to be smaller than 1 cm. and located more than 2 cm. lateral to the spine. ESWL was performed with the Dornier HM3 lithotriptor. One patient in the in situ ESWL group had to be treated twice because disintegration of the stone was insufficient after the initial treatment session. All other patients underwent only 1 treatment session. Because 16 patients were lost to followup, 94 were evaluable for the analysis of immediate and long-term results. For disintegration of the stones in situ ESWL needed significantly more shock waves (1,844 +/- 639 versus 1,297 +/- 473, p < 0.001) and a higher voltage (19.5 +/- 1.4 versus 18.7 +/- 0.9 kv., p < 0.001). There were no severe complications in either treatment group. At 3 months 44 of 46 patients (96%) after in situ ESWL and 45 of 48 (94%) after ureteral manipulation before ESWL were free of stones. In view of these results it is suggested that uncomplicated upper ureteral calculi (as defined previously) should be treated first with in situ ESWL, thus, avoiding an invasive procedure.

Adult↗

PubMed1999

Serum prostate-specific antigen and prostate volume predict long-term changes in symptoms and flow rate: results of a four-year, randomized trial comparing finasteride versus placebo. PLESS Study Group.

OBJECTIVES: To determine whether baseline prostate-specific antigen (PSA), in addition to prostate volume, is associated with long-term changes in symptoms and urinary flow rate. METHODS: Three thousand forty men with benign prostatic hyperplasia enrolled in the PLESS trial were randomly assigned to finasteride 5 mg or placebo for 4 years. Symptoms and flow rate were assessed every 4 months, and data were analyzed by dividing the patients into three groups by baseline PSA tertiles (0 to 1.3, 1.4 to 3.2, and 3.3 ng/mL or greater) and baseline prostate volume tertiles (14 to 41, 42 to 57, and 58 to 1 50 mL). RESULTS: After the initial placebo effect, a slow deterioration in symptoms over time was observed in the placebo-treated men with a baseline PSA 1.4 ng/mL or greater. However, placebo-treated men in the lowest PSA tertile (less than 1.4 ng/mL) had sustained symptomatic improvement that was not seen in placebo-treated men in the higher tertiles (P<0.001). In all finasteride-treated groups, there was initial improvement followed by maintenance or continued symptom improvement over time (approximately 3 to 3.5 points by the end of 4 years). The differences in symptom score improvement between placebo and finasteride were marginal for men with baseline PSA levels less than 1.4 ng/mL (P = 0.128) but were highly significant for men with PSA levels 1.4 ng/mL or greater (P<0.001). Urinary flow rate results were similar to those observed for symptoms. Analysis of symptom and flow rate data by prostate volume tertiles in a 10% subset of men yielded similar results, namely a deterioration of symptoms and flow rate in the two higher tertiles treated with placebo (greater than 41 mL) and a sustained improvement in all three groups of finasteride-treated patients. CONCLUSIONS: Baseline PSA and prostate volume are good predictors of long-term symptomatic and flow rate changes. Baseline PSA levels of 1.4 ng/mL or greater and enlarged prostate glands predict the best long-term response to finasteride compared with placebo.

Enzyme Inhibitors↗

PubMed2002

Prostate cancer radiation dose response: results of the M. D. Anderson phase III randomized trial.

PURPOSE: A randomized radiotherapy dose escalation trial was undertaken between 1993 and 1998 to compare the efficacy of 70 vs. 78 Gy in controlling prostate cancer. METHODS AND MATERIALS: A total of 305 Stage T1-T3 patients were entered into the trial and, of these, 301 with a median follow-up of 60 months, were assessable. Of the 301 patients, 150 were in the 70 Gy arm and 151 were in the 78 Gy arm. The primary end point was freedom from failure (FFF), including biochemical failure, which was defined as 3 rises in the prostate-specific antigen (PSA) level. Kaplan-Meier survival analyses were calculated from the completion of radiotherapy. The log-rank test was used to compare the groups. Cox proportional hazard regression analysis was used to examine the independence of study randomization in multivariate analysis. RESULTS: There was an even distribution of patients by randomization arm and stage, Gleason score, and pretreatment PSA level. The FFF rates for the 70- and 78 Gy arms at 6 years were 64% and 70%, respectively (p = 0.03). Dose escalation to 78 Gy preferentially benefited those with a pretreatment PSA >10 ng/mL; the FFF rate was 62% for the 78 Gy arm vs. 43% for those who received 70 Gy (p = 0.01). For patients with a pretreatment PSA 10 ng/mL who were treated to 78 Gy (98% vs. 88% at 6 years, p = 0.056). Rectal side effects were also significantly greater in the 78 Gy group. Grade 2 or higher toxicity rates at 6 years were 12% and 26% for the 70 Gy and 78 Gy arms, respectively (p = 0.001). Grade 2 or higher bladder complications were similar at 10%. For patients in the 78 Gy arm, Grade 2 or higher rectal toxicity correlated highly with the proportion of the rectum treated to >70 Gy. CONCLUSION: An increase of 8 Gy resulted in a highly significant improvement in FFF for patients at intermediate-to-high risk, although the rectal reactions were also increased. Dose escalation techniques that limit the rectal volume that receives >or=70 Gy to <25% should be used.

Aged↗

PubMed1998

Comparison of the use of a foot pump with the use of low-molecular-weight heparin for the prevention of deep-vein thrombosis after total hip replacement. A prospective, randomized trial.

We conducted a prospective, randomized trial to compare the safety and effectiveness of the A-V Impulse System foot pump with that of low-molecular-weight heparin for reducing the prevalence of deep-vein thrombosis after total hip replacement. Of 290 patients who were to have a primary total hip replacement, 143 were randomized to receive enoxaparin (forty milligrams daily) for seven days after the operation and 147, to use the foot pump for seven days. The primary outcome measure was the prevalence of deep-vein thrombosis, as determined by venography on the sixth, seventh, or eighth postoperative day. Secondary outcome measures included transfusion requirements, intraoperative blood loss, postoperative drainage, blood-loss index, appearance of the site of the wound according to a subjective visual-analog scale, and swelling of the thigh. The patients' compliance with the regimen for use of the foot pump was monitored with an internal timing device, and their acceptance of the device was assessed with a questionnaire. Symptoms consistent with pulmonary embolism were investigated with ventilation-perfusion scanning. The patients were contacted later for detection of symptoms of venous thromboembolism that may have occurred during the first three months after discharge from the hospital. Venography was performed on 274 patients: 136 who used the foot pump and 138 who received enoxaparin. Deep-vein thrombosis was detected in twenty-four (18 per cent) of the patients who used the foot pump compared with eighteen patients (13 per cent) who received enoxaparin (95 per cent confidence interval for the difference in proportions, -3.9 to +13.0 per cent). Thrombosis in the calf was found in seven patients (5 per cent) in the former group compared with six patients (4 per cent) in the latter (95 per cent confidence interval for the difference, -4.2 to +5.8 per cent), and proximal thrombosis was observed in seventeen patients (13 per cent) in the former group compared with twelve patients (9 per cent) in the latter (95 per cent confidence interval for the difference, -3.5 to +11.1 per cent). None of these differences was significant. No patient in either group had major proximal deep-vein thrombosis; all proximal thrombi were isolated entities involving the femoral valve cusp and were of unknown importance. One patient who used the foot pump had a non-fatal pulmonary embolism. One patient who received enoxaparin had a symptomatic deep-vein thrombosis during hospitalization. Two patients (one from each group [0.7 per cent]) were readmitted to the hospital because of a symptomatic deep-vein thrombosis despite normal venographic findings at the time of discharge. There was no difference in the transfusion requirements or the intraoperative blood loss between the two groups. There were more soft-tissue side effects in the patients who received enoxaparin than in those who used the foot pump: there was more bruising of the thigh and oozing of the wound (p < 0.001 for each), postoperative drainage (578 compared with 492 milliliters; p = 0.014), and swelling of the thigh (twenty compared with ten millimeters; p = 0.03). Of 124 patients who used the foot pump and were asked about the acceptability of the device, fourteen (11 per cent) said that it was uncomfortable, twenty-one (17 per cent) reported sleep disturbance, and four (3 per cent) stated that they had stopped using the device. Conversely, ten (8 per cent) found it relaxing. We concluded that the foot pump is a suitable alternative to low-molecular-weight heparin for prophylaxis against thromboembolism after total hip replacement and that it produces fewer soft-tissue side effects. Tolerance of the device is a problem for some patients.

Aged↗

PubMed2001

Interferon as therapy for multiple myeloma: an individual patient data overview of 24 randomized trials and 4012 patients.

Many randomized trials have evaluated alpha-interferon as myeloma therapy, some suggesting a benefit and others not. Most were too small to give reliable answers, so a systematic overview has been performed to provide a more reliable estimate of the effect of interferon. The main end-points were response rates (induction trials), progression-free survival (PFS) and overall survival (OS). Individual patient data were supplied for 24 trials involving 4012 patients, 12 induction trials (2469 patients) and 12 maintenance trials (1543 patients). In induction, response rates were slightly better with interferon (57.5% versus 53.1%, P = 0.01). PFS was better with interferon (33% versus 24% at 3 years, P < 0.00001), an effect seen in both induction (P = 0.0003) and maintenance (P < 0.00001) trials. Median time to progression was increased by about 6 months in both settings. OS was somewhat better with interferon (53% versus 49% at 3 years, P = 0.01) with median survival increased by about 4 months. This benefit was restricted to the smaller trials. The effect of interferon was not significantly related to the dose or duration of interferon or to patients' characteristics. PFS was improved with interferon, but the survival benefit, if any, was small and needs balancing against cost and toxicity.

Adjuvants, Immunologic↗

PubMed2003

Gemcitabine plus cisplatin vs. gemcitabine plus carboplatin in stage IIIb and IV non-small cell lung cancer: a phase III randomized trial.

PURPOSE: This randomized, multicenter, phase III trial was conducted to compare the tolerability of gemcitabine plus cisplatin (GP) vs. gemcitabine plus carboplatin (GC) in chemonaive patients with stage IIIb and IV non-small cell lung carcinoma (NSCLC). Secondary objectives were to evaluate response, duration of response, time to progressive disease (TTPD), and survival. PATIENTS AND METHODS: Eligible patients were required to have stage IIIb or IV NSCLC, no previous chemotherapy, Karnofsky performance status of at least 70, bidimensionally measurable disease, and age 18-75 years. Randomized patients in both arms were given gemcitabine 1200 mg/m(2) on days 1 and 8, followed on day 1 by cisplatin 80 mg/m(2) (GP) or carboplatin AUC=5 (GC). Treatment cycles were repeated every 21 days for a maximum of six cycles, or until disease progression or unacceptable toxicity occurred. RESULTS: Enrolled patients in both arms, 87 in GP and 89 in GC, were well balanced for demographics and disease characteristics. Dose intensity was 93.8 and 92.7% for gemcitabine in GP/GC arms, respectively; 97.7% for cisplatin and 99.9% for carboplatin. Patients with at least one grade 3/4 toxicity excluding nausea, vomiting or alopecia, were 44% in GP arm and 54% in GC arm. The only significantly different toxicities were, nausea and vomiting in GP and thrombocytopenia in GC group. The overall response rates, median TTPD, response duration and survival were, 41/29%, 5.87/4.75 months, 7.48/5.15 months, and 8.75/7.97 months for GP and GC arms, respectively. CONCLUSION: GP and GC are effective and feasible regimens for advanced NSCLC, and are comparable in efficacy and toxicity. GC may offer acceptable option to patients with advanced NSCLC, especially those who are unable to receive cisplatin.

Adult↗

PubMed1993

Terlipressin plus transdermal nitroglycerin vs. octreotide in the control of acute bleeding from esophageal varices: a multicenter randomized trial.

We undertook a multicenter randomized trial to compare the efficacy of terlipressin combined with transdermal nitroglycerin and that of octreotide in the emergency control of acute variceal hemorrhage in cirrhosis. Over 16 mo, 87 patients with endoscopically proved active bleeding from esophageal or cardiac varices were enrolled in five centers in France and randomly assigned to receive intravenous terlipressin (2 mg and then 1 mg/4 hr over 24 hr) and transdermal nitroglycerin (10 mg/12 hr over 24 hr) (group 1) or octreotide (continuous intravenous infusion of 25 micrograms/hr over 12 hr and then 100 micrograms at hr 12 and hr 18 subcutaneously) (group 2). Initial control of bleeding was assessed at the end of 12 hr of treatment on the basis of stability of blood pressure and hematocrit level with no further transfusion requirements. At 12 hr, bleeding was controlled in 59% (24 of 41) in group 1 and 78% (36/46) of group 2 patients (Fisher's exact test, p = 0.064). Mean transfusion requirements over this 12-hr period were significantly greater in group 1 (three blood units; range = 0 to 13) than in group 2 (one blood unit; range = 0 to 5) (p = 0.002). After the first 12 hr, 20% of patients (5 of 24) had repeat bleeding in group 1 compared with 27% (10 of 36) in group 2. During the first 48-hr period, five patients (12%) died in group 1, compared with 3 (6%) in group 2. Few side effects were noted in either group. However, in group 1 two patients experienced severe bradycardia; it resulted in death in one patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗

PubMed2006

Interval estimation of risk ratio in the simple compliance randomized trial.

Consider the simple compliance randomized trial (SCRT), in which patients assigned to an experimental group may switch to receive a control treatment, but patients assigned to a control group are assumed to all receive their assigned treatment. We develop five asymptotic interval estimators for the relative risk (RR) of probabilities of response among patients who would comply with the experimental treatment under the SCRT. We employ Monte Carlo simulation to evaluate the performance of these interval estimators in a variety of situations. We note that the interval estimator using Wald's statistic and the interval estimator derived from a quadratic equation based on asymptotic properties of the maximum likelihood estimator (MLE) can lose accuracy, while the most commonly-used interval estimator using a logarithmic transformation of the MLE for the RR suggested elsewhere can lose efficiency. We further note that the probability of failure to apply the interval estimator derived from an idea used in Fieller's Theorem to produce a confidence interval can be non-negligible even when the number of patients in both comparison groups is not small. Finally, we find that an interval estimator using a simple ad hoc procedure of combining two interval estimators with and without a logarithmic transformation of the MLE can consistently perform well with respect to the coverage probability even when the number of patients per treatment is not large. In fact, this estimator uniformly outperforms all the other estimators considered here and thereby is recommended for general use. We include an example regarding the study of vitamin A supplementation to reduce the mortality among preschool children to illustrate the use of interval estimators discussed in this paper.

Algorithms↗

PubMed2005

Prone positioning improves oxygenation in post-traumatic lung injury--a prospective randomized trial.

BACKGROUND: In a prospective randomized trial the effect of prone positioning on the duration of mechanical ventilation was evaluated in multiple trauma patients and was compared with patients ventilated in supine position. METHOD: Multiple trauma patients of the intensive care units of two university hospitals were considered eligible if they met the criteria for acute lung injury or the acute respiratory distress syndrome. Patients in the prone group (N = 21) were kept prone for at least eight hours and a maximum of 23 hours per day. Prone positioning was continued until a PaO2:FiO2 ratio of more than 300 was present in prone as well as supine position over a period of 48 hours. Patients in the supine group (N = 19) were positioned according to standard care guidelines. RESULTS: The duration of ventilatory support did not differ significantly (30 +/- 17 days in the prone group and 33 +/- 23 days in the supine group). Worst case analysis (death and deterioration of gas exchange) displayed ventilatory support for 41 +/- 29 days in the prone group and 61 +/- 35 days in the supine group (p = 0.06). The PaO2:FiO2 ratio increased significantly more in the prone group in the first four days (p = 0.03). The prevalence of Acute Respiratory Distress Syndrome (ARDS) following acute lung injury (p = 0.03) and the prevalence of pneumonia (p = 0.048) were reduced also. One patient in the prone and three patients in the supine group died due to multi organ failure (p = 0.27). CONCLUSIONS: Intermittent prone positioning was not able to reduce the duration of mechanical ventilation in this limited number of patients. However the oxygenation improved significantly over the first four days of treatment, and the prevalence of ARDS and pneumonia were reduced.

Adult↗

PubMed2002

Statistical issues in randomized trials of cancer screening.

BACKGROUND: The evaluation of randomized trials for cancer screening involves special statistical considerations not found in therapeutic trials. Although some of these issues have been discussed previously, we present important recent and new methodologies. METHODS: Our emphasis is on simple approaches. RESULTS: We make the following recommendations: (1) Use death from cancer as the primary endpoint, but review death records carefully and report all causes of death; (2) Use a simple "causal" estimate to adjust for nonattendance and contamination occurring immediately after randomization; (3) Use a simple adaptive estimate to adjust for dilution in follow-up after the last screen CONCLUSION: The proposed guidelines combine recent methodological work on screening endpoints and noncompliance/contamination with a new adaptive method to adjust for dilution in a study where follow-up continues after the last screen. These guidelines ensure good practice in the design and analysis of randomized trials of cancer screening.

Endpoint Determination↗

PubMed2005

Randomized trial of lifestyle modification and pharmacotherapy for obesity.

BACKGROUND: Weight-loss medications are recommended as an adjunct to a comprehensive program of diet, exercise, and behavior therapy but are typically prescribed with minimal or no lifestyle modification. This practice is likely to limit therapeutic benefits. METHODS: In this one-year trial, we randomly assigned 224 obese adults to receive 15 mg of sibutramine per day alone, delivered by a primary care provider in eight visits of 10 to 15 minutes each; lifestyle-modification counseling alone, delivered in 30 group sessions; sibutramine plus 30 group sessions of lifestyle-modification counseling (i.e., combined therapy); or sibutramine plus brief lifestyle-modification counseling delivered by a primary care provider in eight visits of 10 to 15 minutes each. All subjects were prescribed a diet of 1200 to 1500 kcal per day and the same exercise regimen. RESULTS: At one year, subjects who received combined therapy lost a mean (+/-SD) of 12.1+/-9.8 kg, whereas those receiving sibutramine alone lost 5.0+/-7.4 kg, those treated by lifestyle modification alone lost 6.7+/-7.9 kg, and those receiving sibutramine plus brief therapy lost 7.5+/-8.0 kg (P<0.001). Those in the combined-therapy group who frequently recorded their food intake lost more weight than those who did so infrequently (18.1+/-9.8 kg vs. 7.7+/-7.5 kg, P=0.04). CONCLUSIONS: The combination of medication and group lifestyle modification resulted in more weight loss than either medication or lifestyle modification alone. The results underscore the importance of prescribing weight-loss medications in combination with, rather than in lieu of, lifestyle modification.

Adult↗

PubMed2005

Randomized trial of pegylated interferon alpha-2b monotherapy in haemodialysis patients with chronic hepatitis C.

BACKGROUND: Chronic hepatitis C infection is prevalent among haemodialysis patients. The goal of our study was to determine the efficacy and safety of pegylated interferon alpha-2b in haemodialysis patients with chronic hepatitis C. METHODS: We conducted a trial which randomized haemodialysis patients with chronic hepatitis C to 1.0 or 0.5 microg/kg of pegylated interferon alpha-2b subcutaneously, weekly for up to 48 weeks. End-points were sustained viral response and adverse events. Data were analysed as intention to treat and as intended per protocol. RESULTS: After 16 patients were enrolled, the study was terminated because of adverse events and modifications needed in the study design. Nine subjects were randomized to the 1.0 microg/kg group and seven subjects were randomized to the 0.5 microg/kg group. Serious adverse events requiring discontinuation of therapy occurred in five (56%) subjects in the 1.0 microg/kg group and in two (28%) subjects in the 0.5 microg/kg group (P = 0.36). The most common adverse events were hypertension and infection unrelated to neutropenia. Two (22%) subjects in the 1.0 microg/kg group, both genotype 1, had a sustained viral response, and none of the subjects in the 0.5 microg/kg group had a sustained viral response (P = 0.47). Five subjects in the 1.0 microg/kg group were able to complete 24 weeks or longer of therapy as per protocol and two (40%) were sustained responders. CONCLUSIONS: In our study group, pegylated interferon alpha-2b was poorly tolerated and was associated with substantial side effects. Sustained response rates seen with pegylated interferon in our study do not appear to be better than rates reported for standard interferon alpha-2b.

Adult↗

PubMed1998

Economic evaluation of chemotherapy with mitoxantrone plus prednisone for symptomatic hormone-resistant prostate cancer: based on a Canadian randomized trial with palliative end points.

PURPOSE: To evaluate the economic consequences of the use of chemotherapy in patients with symptomatic hormone-resistant prostate cancer (HRPC) in the context of a previously published Canadian open-label, phase III, randomized trial with palliative end points. PATIENTS AND METHODS: The trial randomized 161 patients to initial treatment with mitoxantrone and prednisone (M + P) or to prednisone alone (P) and showed better palliation with M + P. There was no significant difference in survival. A detailed retrospective chart review was performed of resources used from randomization until death of 114 of 161 patients enrolled at the three largest centers: these included hospital admissions, outpatient visits, investigations, therapies (which included all chemotherapy and radiation), and palliative care. Cancer center and community hospital costs were calculated by using the hotel approximation method and case costing from the Ontario Case Cost Project, respectively. Cost-utility analysis was performed by transforming the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 global quality-of-life item measured every 3 weeks on trial to an estimate of utility, and extending the last known value through to death or last follow-up. RESULTS: The mean total cost until death or last follow-up by intention-to-treat was M + P CDN $27,300; P CDN $29,000. The 95% confidence intervals on the observed cost difference ranged from a saving of $9,200 for M + P (with palliative benefit) to an increased cost of $5,800 for M + P. The major proportion of cost (M + P 53% v P 66%; CDN $14,500 v $19,100) was for inpatient care. Initial M + P was consistently less expensive in whichever time period was used to compare costs. Cost-utility analysis showed M + P to be the preferred strategy with an upper 95% confidence interval for the incremental cost-utility ratio of CDN $19,700 per quality-adjusted life-year (QALY). CONCLUSION: A treatment that reduces symptoms and improves quality of life has the potential to reduce costs in other areas. Economic factors should not influence the clinical decision as to whether to use M + P in a symptomatic patient.

Canada↗

PubMed2005

Simple adjustments for randomized trials with nonrandomly missing or censored outcomes arising from informative covariates.

In randomized trials with missing or censored outcomes, standard maximum likelihood estimates of the effect of intervention on outcome are based on the assumption that the missing-data mechanism is ignorable. This assumption is violated if there is an unobserved baseline covariate that is informative, namely a baseline covariate associated with both outcome and the probability that the outcome is missing or censored. Incorporating informative covariates in the analysis has the desirable result of ameliorating the violation of this assumption. Although this idea of including informative covariates is recognized in the statistics literature, it is not appreciated in the literature on randomized trials. Moreover, to our knowledge, there has been no discussion on how to incorporate informative covariates into a general likelihood-based analysis with partially missing outcomes to estimate the quantities of interest. Our contribution is a simple likelihood-based approach for using informative covariates to estimate the effect of intervention on a partially missing outcome in a randomized trial. The first step is to create a propensity-to-be-missing score for each randomization group and divide the scores into a small number of strata based on quantiles. The second step is to compute stratum-specific estimates of outcome derived from a likelihood-analysis conditional on the informative covariates, so that the missing-data mechanism is ignorable. The third step is to average the stratum-specific estimates and compute the estimated effect of intervention on outcome. We discuss the computations for univariate, survival, and longitudinal outcomes, and present an application involving a randomized study of dual versus triple combinations of HIV-1 reverse transcriptase inhibitors.

Acquired Immunodeficiency Syndrome↗