Recent trials suggest that off-pump coronary artery bypass grafting (OPCAB) reduces the risk of mortality and morbidity compared with conventional coronary artery bypass grafting (CCAB) using cardiopulmonary bypass. Patients with a moderate- to high-risk of complications after CCAB may have additional benefit from OPCAB.
The Best Bypass Surgery Trial is a randomized, single center trial comparing the effects of OPCAB versus CCAB. The inclusion criteria are 3 vessel coronary heart disease affecting one of the marginal arteries, age>54 years, and EuroSCORE>or=5. The primary composite outcome measure consists of all-cause mortality, myocardial infarction, stroke, cardiac arrest, cardiogenic shock, and cardiac revascularization procedure. Follow up involves collection of data of mortality and morbidity via linkage to public registers, quality of life assessment at 3 and 12 months postoperatively and angiographic control at 12 months. The sample size of 330 patients was based on an estimated 75% one-year event free rate of the primary outcome measure in the OPCAB arm and 60% in the control arm with alpha=.05 and beta=.20. Accordingly, the trial will be able to detect an absolute risk reduction of 15% or a relative risk reduction of 37.5%. The median follow-up time is scheduled to 3 years.
Enrollment started in April 2002 and ended March 2006.
The results may have implications on the treatment modality of moderate- to high-risk patients scheduled for coronary artery bypass grafting.
To assess the effects of comprehensive cardiac rehabilitation compared with usual care on physical activity and mental health for patients treated with catheter ablation for atrial fibrillation.
The patients were randomized 1:1 stratified by paroxysmal or persistent atrial fibrillation and sex to cardiac rehabilitation consisting of 12 weeks physical exercise and four psycho-educational consultations plus usual care (cardiac rehabilitation group) versus usual care. The primary outcome was Vo2 peak. The secondary outcome was self-rated mental health measured by the Short Form-36 questionnaire. Exploratory outcomes were collected.
210 patients were included (mean age: 59 years, 74% men), 72% had paroxysmal atrial fibrillation prior to ablation. Compared with usual care, the cardiac rehabilitation group had a beneficial effect on Vo2 peak at four months (24.3mL kg(-1) min(-1) versus 20.7mL kg(-1) min(-1), p of main effect=0.003, p of interaction between time and intervention=0.020). No significant difference between groups on Short Form-36 was found (53.8 versus 51.9 points, P=.20). Two serious adverse events (atrial fibrillation in relation to physical exercise and death unrelated to rehabilitation) occurred in the cardiac rehabilitation group versus one in the usual care group (death unrelated to intervention) (P=.56). In the cardiac rehabilitation group 16 patients versus 7 in the usual care group reported non-serious adverse events (P=.047).
Comprehensive cardiac rehabilitation had a positive effect on physical capacity compared with usual care, but not on mental health. Cardiac rehabilitation caused more non-serious adverse events.
Patients with chronic autoimmune thyroiditis have impaired health-related quality of life. The thyroid gland has a high selenium concentration, and specific selenoprotein enzyme families are crucial to immune function, and catalyze thyroid hormone metabolism and redox processes in thyroid cells. Previous randomized controlled trials have found that selenium supplementation decreases thyroid-disease-specific antibody levels. We hypothesize that selenium might be beneficial in the treatment of chronic autoimmune thyroiditis.
The CATALYST trial is an investigator-initiated randomized, blinded, multicentre clinical trial of selenium supplementation versus placebo in patients with chronic autoimmune thyroiditis.
age =18 years; serum thyroid peroxidase antibody level =100 IU/ml within the previous 12 months; treatment with levothyroxine and written informed consent.
previous diagnosis of toxic nodular goitre, Graves' hyperthyroidism, postpartum thyroiditis, Graves' orbitopathy; previous antithyroid drug treatment, radioiodine therapy or thyroid surgery; immune-modulatory or other medication affecting thyroid function; pregnancy, planned pregnancy or breastfeeding; allergy towards any intervention or placebo component; intake of selenium supplementation >55 µg/day; inability to read or understand Danish or lack of informed consent. The trial will include 2?×?236 participants. The experimental intervention and control groups will receive 200 µg selenium-enriched yeast or matching placebo tablets daily for 12 months. The experimental supplement will be SelenoPrecise®. The primary outcome is thyroid-related quality of life assessed by the Thyroid Patient-Reported Outcome (ThyPRO) questionnaire. Secondary outcomes include serum thyroid peroxidase antibody concentration; serum triiodothyronine/thyroxine ratio; levothyroxine dosage; adverse reactions and serious adverse reactions and events.
In this pragmatic trial, participating patients follow their usual treatment at their usual hospitals. In order to collect high-quality data on the clinical course and quality of life, and to minimize missing data, an elaborate trial management system has been designed. 12 months intervention duration was selected in consideration of the primary outcome, thyroid-related quality of life.
The CLARICOR trial reported that clarithromycin compared with placebo increased all-cause mortality in patients with stable coronary heart disease. This study investigates the effects of clarithromycin versus placebo during 10years follow up.
The CLARICOR trial is a randomised, placebo-controlled trial including 4373 patients with stable coronary heart disease. The interventions were 2weeks of clarithromycin 500mg a day versus placebo. 10year follow up was performed through Danish public registers and analysed with Cox regression.
Clarithromycin increased all-cause mortality (hazard ratio (HR): 1.10, 95% confidence interval (CI): 1.00-1.21) and cerebrovascular disease during 10years (HR: 1.19, 95% CI: 1.02-1.38). The increased mortality and morbidity were restricted to patients not on statin at entry (HR: 1.16, 95% CI: 1.04-1.31, and HR: 1.25, 95% CI: 1.03-1.50). The assumption of constant HR during the 10years was violated for cardiovascular death (P=0.01) and cardiovascular death outside hospital (P
Cognitive training plus a comprehensive psychosocial programme (OPUS) versus the comprehensive psychosocial programme alone for patients with first-episode schizophrenia (the NEUROCOM trial): a study protocol for a centrally randomised, observer-blinded multi-centre clinical trial.
Up to 85% of patients with schizophrenia demonstrate cognitive dysfunction in at least one domain. Cognitive dysfunction plays a major role in functional outcome. It is hypothesized that addition of cognitive training to a comprehensive psychosocial programme (OPUS) enhances both cognitive and everyday functional capacity of patients more than the comprehensive psychosocial programme alone.
The NEUROCOM trial examines the effect on cognitive functioning and everyday functional capacity of patients with schizophrenia of a 16-week manualised programme of individual cognitive training integrated in a comprehensive psychosocial programme versus the comprehensive psychosocial programme alone. The cognitive training consists of four modules focusing on attention, executive functioning, learning, and memory. Cognitive training involves computer-assisted training tasks as well as practical everyday tasks and calendar training. It takes place twice a week, and every other week the patient and trainer engage in a dialogue on the patient's cognitive difficulties, motivational goals, and progress in competence level. Cognitive training relies on errorless learning principles, scaffolding, and verbalisation in its effort to improve cognitive abilities and teach patients how to apply compensation strategies as well as structured problem solving techniques. At 16-week post-training and at ten-months follow-up, assessments are conducted to investigate immediate outcome and possible long-term effects of cognitive training. We conduct blinded assessments of cognition, everyday functional capacity and associations with the labour market, symptom severity, and self-esteem.
Results from four-month and ten-month follow-ups have the potential of reliably providing documentation of the long-term effect of CT for patients with schizophrenia.
Cites: Control Clin Trials. 2000 Jun;21(3):167-8910822117
The aim of this randomised clinical trial was to assess a comprehensive cardiac rehabilitation intervention including exercise training and psycho-education vs 'treatment as usual' in patients treated with an implantable cardioverter defibrillator (ICD).
In this study 196 patients with first time ICD implantation (mean age 57.2 (standard deviation (SD)=13.2); 79% men) were randomised (1:1) to comprehensive cardiac rehabilitation vs 'treatment as usual'. Altogether 144 participants completed the 12 month follow-up. The intervention consisted of twelve weeks of exercise training and one year of psycho-educational follow-up focusing on modifiable factors associated with poor outcomes. Two primary outcomes, general health score (Short Form-36 (SF-36)) and peak oxygen uptake (VO2), were used. Post-hoc analyses included SF-36 and ICD therapy history.
Comprehensive cardiac rehabilitation significantly increased VO2 uptake after exercise training to 23.0 (95% confidence interval (CI) 20.9-22.7) vs 20.8 (95% CI 18.9-22.7) ml/min/kg in the control group (p=0.004 (multiplicity p=0.015)). Comprehensive cardiac rehabilitation significantly increased general health; at three months (mean 62.8 (95% CI 58.1-67.5) vs 64.4 (95% CI: 59.6-69.2)) points; at six months (mean 66.7 (95% CI 61.5-72.0) vs 61.9 (95% CI 56.1-67.7) points); and 12 months (mean 63.5 (95% CI 57.7-69.3) vs 62.1 (95% CI 56.2-68.0)) points (p
Advanced cancer patients experience considerable symptoms, problems, and needs. Early referral of these patients to specialized palliative care (SPC) could offer improvements. The Danish Palliative Care Trial (DanPaCT) investigates whether patients with metastatic cancer will benefit from being referred to 'early SPC'. DanPaCT is a multicenter, parallel-group, superiority clinical trial with 1:1 randomization. The planned sample size was 300 patients. The primary data collection for DanPaCT is finished. To prevent outcome reporting bias, selective reporting, and data-driven results, we present a detailed statistical analysis plan (SAP) for DanPaCT here.
This SAP provides detailed descriptions of the statistical analyses of the primary and secondary outcomes in DanPaCT. The primary outcome is the change in the patient's 'primary need'. The 'primary need' is a patient-individualised outcome representing the score of the symptom or problem that had the highest intensity out of seven at baseline assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Secondary outcomes are the seven scales that are represented in the primary outcome, but each scale evaluated individually for all patients, and survival. The detailed description includes chosen significance levels, models for multiple imputations, sensitivity analyses and blinding. In addition, we discuss the patient-individualized primary outcome, blinding, missing data, multiplicity and the risk of bias.
Only few trials have investigated the effects of SPC. To our knowledge DanPaCT is the first trial to investigate screening based 'early SPC' for patients with metastatic cancer from a broad spectrum of cancer diagnosis.
Heart valve diseases are common with an estimated prevalence of 2.5% in the Western world. The number is rising due to an ageing population. Once symptomatic, heart valve diseases are potentially lethal, and heavily influence daily living and quality of life. Surgical treatment, either valve replacement or repair, remains the treatment of choice. However, post surgery, the transition to daily living may become a physical, mental and social challenge. We hypothesise that a comprehensive cardiac rehabilitation programme can improve physical capacity and self-assessed mental health and reduce hospitalisation and healthcare costs after heart valve surgery.
A randomised clinical trial, CopenHeartVR, aims to investigate whether cardiac rehabilitation in addition to usual care is superior to treatment as usual after heart valve surgery. The trial will randomly allocate 210 patients, 1:1 intervention to control group, using central randomisation, and blinded outcome assessment and statistical analyses. The intervention consists of 12 weeks of physical exercise, and a psycho-educational intervention comprising five consultations. Primary outcome is peak oxygen uptake (VO2 peak) measured by cardiopulmonary exercise testing with ventilatory gas analysis. Secondary outcome is self-assessed mental health measured by the standardised questionnaire Short Form 36. Also, long-term healthcare utilisation and mortality as well as biochemistry, echocardiography and cost-benefit will be assessed. A mixed-method design is used to evaluate qualitative and quantitative findings encompassing a survey-based study before the trial and a qualitative pre- and post-intervention study.
The study is approved by the local regional Research Ethics Committee (H-1-2011-157), and the Danish Data Protection Agency (j.nr. 2007-58-0015).
The Danish OPUS I trial randomized 547 patients with first-episode psychosis to a two-year early-specialised assertive treatment programme (OPUS) versus standard treatment. The two years OPUS treatment had significant positive effects on psychotic and negative symptoms, secondary substance abuse, treatment adherence, lower dosage of antipsychotic medication, and a higher treatment satisfaction. However, three years after end of the OPUS treatment, the positive clinical effects were not sustained, except that OPUS-treated patients were significantly less likely to be institutionalised compared with standard-treated patients. The major objective of the OPUS II trial is to evaluate the effects of five years of OPUS treatment versus two years of OPUS treatment.
The OPUS II trial is designed as a randomized, open label, parallel group trial with blinded outcome assessment. Based on our sample size estimation, 400 patients treated in OPUS for two years will be randomized to further three years of OPUS treatment versus standard treatment. The specialized assertive OPUS treatment consists of three core elements: assertive community treatment, psycho-educational family treatment, and social skills training.
It has been hypothesized that there is a critical period from onset up to five years, which represents a window of opportunity where a long-term course can be influenced. Extending the specialized assertive OPUS treatment up to five years may allow the beneficial effects to continue beyond the high-risk period, through consolidation of improved social and functional outcome.