Controlled clinical trials最新文献

STAR*D is a multisite, prospective, randomized, multistep clinical trial of outpatients with nonpsychotic major depressive disorder. The study compares various treatment options for those who do not attain a satisfactory response with citalopram, a selective serotonin reuptake inhibitor antidepressant. The study enrolls 4000 adults (ages 18–75) from both primary and specialty care practices who have not had either a prior inadequate response or clear-cut intolerance to a robust trial of protocol treatments during the current major depressive episode. After receiving citalopram (level 1), participants without sufficient symptomatic benefit are eligible for randomization to level 2 treatments, which entail four switch options (sertraline, bupropion, venlafaxine, cognitive therapy) and three citalopram augment options (bupropion, buspirone, cognitive therapy). Those who receive cognitive therapy (switch or augment options) at level 2 without sufficient improvement are eligible for randomization to one of two level 2A switch options (venlafaxine or bupropion). Level 2 and 2A participants without sufficient improvement are eligible for random assignment to two switch options (mirtazapine or nortriptyline) and to two augment options (lithium or thyroid hormone) added to the primary antidepressant (citalopram, bupropion, sertraline, or venlafaxine) (level 3). Those without sufficient improvement at level 3 are eligible for level 4 random assignment to one of two switch options (tranylcypromine or the combination of mirtazapine and venlafaxine). The primary outcome is the clinician-rated, 17-item Hamilton Rating Scale for Depression, administered at entry and exit from each treatment level through telephone interviews by assessors masked to treatment assignments. Secondary outcomes include self-reported depressive symptoms, physical and mental function, side-effect burden, client satisfaction, and health care utilization and cost. Participants with an adequate symptomatic response may enter the 12-month naturalistic follow-up phase with brief monthly and more complete quarterly assessments.

The objective of the study was to determine the effectiveness and cost-effectiveness of primary care and community-oriented interventions in managing HbA_1c, blood pressure, and lipids, and reducing hospitalizations and emergency room visits over 2 years. We describe an ongoing, randomized controlled trial of 542 urban African-Americans with type 2 diabetes ages 25 years and older who are members of a university-affiliated managed-care organization in Baltimore, MD. The participants are 74% female, have a mean age of 58 years, and 35% have yearly incomes greater than US$7500. Participants were randomized to one of two intervention groups for a period of 2 years: (1) usual medical care plus minimal telephone intervention implemented by a trained lay health educator (control group) or (2) usual medical care plus intensive intervention implemented by a nurse case manager (NCM)/community health worker (CHW) team. The intensive NCM/CHW team executes individual plans of care using evidence-based algorithms that focus on traditional diabetes self-management, screening and management of diabetes-related complications, and social issues surrounding diabetes care. Face-to-face NCM visits are conducted in the clinic once per year and CHW visits are conducted in the participant's home one to three times per year, both with additional follow-up contacts as needed. Written and verbal feedback (when necessary) is provided to the participant's primary care physician. All participants are expected to attend a 24-month follow-up visit where data are collected by interviewers blinded to intervention assignment. As of May 1, 2003, recruitment is complete, interventions are being fully implemented, and 24-month follow-up visits are beginning. Baseline sociodemographic characteristics, health-care utilization, health behaviors, and clinical characteristics of the study population are reported. This study is designed to test the hypothesis that a primary-care-based NCM plus CHW team approach is an effective, practical, and economically feasible strategy for translating current knowledge about type 2 diabetes into high-quality health care for urban African-Americans.

Hysterectomy may be overused as treatment for abnormal uterine bleeding due to benign causes in reproductive women. Medical therapies are an alternative, and there is a need for randomized trials comparing the outcomes of these approaches. Women of reproductive age who continued to have bothersome abnormal uterine bleeding after cyclic hormonal treatment with medroxyprogesterone acetate (MPA; 10–20 mg for 10–14 days/month) for 3–5 months were invited to participate in a randomized trial of hysterectomy versus other medical therapies. Participating gynecologists were free to choose the particular surgical (transabdominal or transvaginal) or medical (generally oral contraceptives and/or a prostaglandin synthetase inhibitor) approaches. Outcomes during 2 years of follow-up include quality of life (primary), sexual function, clinical effectiveness and cost. We screened 1557 women to find 413 who began 3–5 months of MPA; 215 completed this treatment, of whom 102 still had bothersome symptoms, and of these 38 consented to be randomized. Another 25 women with bothersome symptoms after a documented history of 3 months of cyclic MPA were also randomized, for a total of 63. The average age of randomized women was 41; 54% were African-American, and they reported uterine bleeding 12 days/month on average, heavy bleeding 6 days/month. Anemia (hematocrit<32) was present in 38% of African-Americans and 15% of Caucasians (p=0.05). Two thirds of the women had fibroids and 80% reported pelvic pain. Obesity was common (45% had a body mass index (BMI)>30), and associated with a longer duration of symptoms (12 vs. 4 years for BMI<25; p=0.02) and a greater prevalence of incontinence (44% vs. 16%; p=0.046). Although recruitment was difficult, we have completed enrollment in a randomized clinical trial comparing surgical and medical treatments for abnormal uterine bleeding.

Hypertension is a major public health problem with serious medical and financial consequences. Barriers to successful conventional pharmacological treatment include side effects, out-of-pocket expenses, patient noncompliance and insufficient dosages. Acupuncture has been studied as an alternative therapy for controlling blood pressure (BP) but previous studies have serious methodological limitations. This paper describes the design of the Stop Hypertension with the Acupuncture Research Program (SHARP) trial, a pilot randomized clinical trial designed to gather preliminary data regarding the efficacy of traditional Chinese medicine (TCM)-based acupuncture for control of essential hypertension. The design of the SHARP trial balanced rigorous clinical trial methodology with principles of TCM. Eligible participants had systolic BP (SBP) 140–179 mm Hg and diastolic BP (DBP) 90–109 mm Hg in the absence of antihypertensive therapy. Following screening, participants were randomized to one of three groups: individualized, standardized or control acupuncture. Treatments were designed according to principles of TCM; nonspecific effects associated with the interventions were standardized across the randomized groups. For individualized acupuncture, points were tailored to each participant. Standardized acupuncture used a prespecified set of points. The invasive sham control acupuncture regimen was designed to be non-active. Each participant received a “prescription” for individualized acupuncture from an acupuncturist who was masked to treatment assignment, and was subsequently treated by an independent acupuncturist. Patients and those assessing BP were masked to treatment group. Acupuncture was delivered twice a week for 6 weeks. Follow-up visits were every 2 weeks to week 10 and then at months 4, 6, 9 and 12. The primary endpoint will be change in SBP from baseline to 10 weeks. DBP, BP trajectories over the 12-month follow-up and antihypertensive medication requirements will also be examined. Initial contact was documented for 1442 prospective participants from March 2001 to April 2002; 424 provided informed consent and 192 were ultimately randomized.

The difference between two proportions is often the focus of interest in prospective comparative studies such as randomized controlled trials that have a binary outcome. Consequently, interval estimation for this parameter has received considerable attention in the literature. A hybrid procedure resulting from combining two sets of confidence limits for a single proportion as proposed by Newcombe has been previously recommended for this purpose because of its superior properties and relative simplicity. In this paper, we propose a simple alternative approach based on Fisher's z transformation. The results of an exact evaluation study show that this new procedure performs as well as Newcombe's procedure in terms of percent coverage and expected confidence interval width. Several examples are presented.

The safety of silver amalgam as a dental restorative material has been controversial since its introduction 150 years ago, but until recently it has been assumed that the exposure to mercury from dental amalgam is limited to the acute placement phase. However, some recent studies have raised safety concerns by demonstrating chronic release of mercury vapor from amalgam fillings during chewing and brushing. The Children's Amalgam Trial is a two-arm randomized trial of safety, comparing amalgam with a mercury-free restorative material. A single masking procedure is used to ensure that all investigators and staff measuring outcomes are unaware of assigned trial arm. The study follows 534 New England children, aged 6–10 years at enrollment, for 5 years. The children were recruited from two northeastern U.S. communities, one in rural Maine and one in urban Massachusetts. No trial subjects received prior amalgam restorations, and all were in need of at least two posterior occlusal fillings. Participants were randomized to receive either amalgam or composite material for all posterior restorations at baseline and at subsequent visits. The primary endpoint will be 5-year change in IQ scores. Secondary endpoints will include measures of other neuropsychological assessments and renal functioning. This paper describes the design of the Children's Amalgam Trial and includes data on baseline characteristics of the subjects.

Matching individuals to multisite cooperative clinical trials can be a complex and nonintuitive decision process that expends considerable time and may be prone to errors. We developed and tested a web-based decision support tool to aid investigators in matching patients to open clinical trials for children with rhabdomyosarcoma in the context of an international cooperative cancer clinical trials network. A decision tree for trial eligibility based on eight clinical variables representing major disease characteristics was translated into a web-based format. In a blinded fashion, we assessed the accuracy of the tool in assigning 100 randomly selected cases to the proper clinical trial. The web-based tool assigned patients to the proper clinical trial in all 100 randomly selected cases. The time needed to enter data and receive results using this tool is about 1 minute per patient entered. It is feasible to develop a web-based tool to help investigators in matching patients to clinical trials. When such decisions are complex and nonintuitive, such tools have the potential to improve the accuracy of clinical trial assignment and save time.

Patients with severe ventricular dysfunction and coronary disease have high morbidity and mortality. They may benefit from revascularization but have significant perioperative morbidity and mortality. Positron emission tomography (PET) imaging with F-18-fluorodeoxyglucose (FDG) can detect viable myocardium that may recover from revascularization in such patients. It is unclear whether use of FDG PET in this population improves outcome or is cost-effective. The principal aim of this study is to determine whether FDG PET-guided therapy improves clinical outcome compared to standard care. Secondary objectives are to determine whether FDG PET-guided therapy improves left ventricular (LV) function, improves quality of life, and provides a cost benefit versus standard care. Included in this multicenter randomized controlled trial are patients with coronary artery disease and severe LV dysfunction who are referred for revascularization, heart failure, or cardiac transplantation or in whom FDG PET is potentially useful. Consenting subjects will be randomized to therapy directed by FDG PET or standard care. The primary outcome is the composite cardiovascular endpoint of cardiac death, myocardial infarction, transplantation, or rehospitalization for unstable angina or heart failure. Secondary outcomes include health-related quality of life, costs, mortality, cardiovascular events, and LV function. Assuming two-sided alpha = 0.05, power = 80%, a sample size of 206 patients per group is required to detect a 15% absolute difference in the primary outcome between PET-directed therapy compared to standard care. Analyses will be conducted on an intention-to-treat basis. To our knowledge, this is the first large trial to evaluate whether FDG PET-directed therapy is effective and provides a cost benefit in patients with severe LV dysfunction. If so, thousands of such patients can be risk-stratified to select who is likely to benefit from revascularization.

Rigid gas permeable (RGP) contact lenses are initially less comfortable to wear than spectacles. In previous studies evaluating the use of RGP contact lenses to control myopia, more subjects randomly assigned to wear RGP contact lenses have been lost to follow-up than spectacle wearers. Previous rigid contact lens myopia control studies have lost 44% and 47% of the rigid contact lens wearers. This unequal loss to follow-up may compromise the results of the study, so we conducted a run-in period prior to randomized treatment-group assignment to ensure that all participants could adapt to RGP contact lens wear. We enrolled 147 children ages 8–11 years with myopia in the run-in period. Of the 147 subjects, 116 (78.9%) were able to wear RGP contact lenses for at least 40 hours per week and reported that they were “usually comfortable” or “always comfortable.” After 3 years, no subjects were lost to follow-up. The run-in period greatly reduced the loss to follow-up suffered by previous RGP contact lens myopia progression studies and may help provide more definitive answers regarding myopia control with RGP contact lenses.