Trials
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Randomized Controlled Trial Multicenter Study Comparative Study
Apixaban versus Antiplatelet drugs or no antithrombotic drugs after anticoagulation-associated intraCerebral HaEmorrhage in patients with Atrial Fibrillation (APACHE-AF): study protocol for a randomised controlled trial.
There is a marked lack of evidence on the optimal prevention of ischaemic stroke and other thromboembolic events in patients with non-valvular atrial fibrillation and a recent intracerebral haemorrhage during treatment with oral anticoagulation. These patients are currently treated with oral anticoagulants, antiplatelet drugs, or no antithrombotic treatment, depending on personal and institutional preferences. Compared with warfarin, the direct oral anticoagulant apixaban reduces the risk of stroke or systemic embolism, intracranial haemorrhage, and case fatality in patients with atrial fibrillation. Compared with aspirin, apixaban reduces the risk of stroke or systemic embolism in patients with atrial fibrillation, and has a similar risk of intracerebral haemorrhage. Novel oral anticoagulants have not been evaluated in patients with atrial fibrillation and a recent intracerebral haemorrhage. To inform a phase III trial, the phase II Apixaban versus Antiplatelet drugs or no antithrombotic drugs after anticoagulation-associated intraCerebral HaEmorrhage in patients with Atrial Fibrillation (APACHE-AF) trial aims to obtain estimates of the rates of vascular death or non-fatal stroke in patients with atrial fibrillation and a recent anticoagulation-associated intracerebral haemorrhage treated with apixaban and in those in whom oral anticoagulation is avoided. ⋯ APACHE-AF is a phase II, multicentre, open-label, parallel-group, randomised clinical trial with masked outcome assessment. One hundred adults with a history of atrial fibrillation and a recent intracerebral haemorrhage during treatment with anticoagulation in whom clinical equipoise exists on the optimal stroke prevention strategy will be enrolled in 14 hospitals in The Netherlands. These patients will be randomly assigned in a 1:1 ratio to either apixaban or to avoiding oral anticoagulation. Patients in the control group may be treated with antiplatelet drugs at the discretion of the treating physician. The primary outcome is the composite of vascular death or non-fatal stroke during follow-up. We aim to include 100 patients in 2.5 years. All patients will be followed-up for the duration of the study, but at least for 1 year. Recruitment commenced in September 2014 and is ongoing. This trial is funded by the Dutch Heart Foundation (2012 T077) and ZonMW (015008048).
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Randomized Controlled Trial Multicenter Study Comparative Study
Safety and efficacy of colistin versus meropenem in the empirical treatment of ventilator-associated pneumonia as part of a macro-project funded by the Seventh Framework Program of the European Commission studying off-patent antibiotics: study protocol for a randomized controlled trial.
Ventilator-associated pneumonia (VAP) is one of the most common and severe hospital-adquired infections, and multidrugresistant gram-negative bacilli (MDR-GNB) constitute the main etiology in many countries. Inappropriate empiric antimicrobial treatment is associated with increased mortality. In this context, the empirical treatment of choice for VAP is unknown. Colistin, is now the antimicrobial with greatest in vitro activity against MDR-GNB. ⋯ Currently, there is no study being undertaken which analyzes empiric treatment of (VAP) with a suspicion of multi-resistance. Colistin, an off-patent antibiotic commercialized for more than 60 years, could widen the antibiotic alternatives for a high-mortality illness aggravated by antibiotic resistance.
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Postoperative delirium (POD) is a manifestation of acute postoperative brain dysfunction that is frequently observed after cardiac surgery. POD is associated with short-term complications such as an increase in mortality, morbidity, costs and length of stay, but can also have long-term sequelae, including persistent cognitive deficits, loss of independence, and increased mortality for up to 2 years. The noble gas xenon has been demonstrated in various models of neuronal injury to exhibit remarkable neuroprotective properties. We therefore hypothesize that xenon anesthesia reduces the incidence of POD in elderly patients undergoing cardiac surgery with the use of cardiopulmonary bypass. ⋯ Older patients undergoing cardiac surgery are at particular risk to develop POD. Xenon provides remarkable hemodynamic stability and has been suggested in preclinical studies to exhibit neuroprotective properties. The present trial will assess whether the promising profile of xenon can be translated into a better outcome in the geriatric population.
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Randomized Controlled Trial
Remote ischemic conditioning in ST-elevation myocardial infarction as adjuvant to primary angioplasty (RIC-STEMI): study protocol for a randomized controlled trial.
ST-elevation myocardial infarction (STEMI) accounts for nearly one third of acute coronary syndromes. Despite improved STEMI patient care, mortality remains high, contributing significantly to the ischemic heart disease burden. This may partly be related to ischemia-reperfusion injury (IRI). Remote ischemic conditioning (RIC), through short cycles of ischemia-reperfusion applied to a limb, has been shown to reduce IRI in various clinical settings. Our primary hypothesis is that RIC will reduce adverse events related to STEMI when applied as adjunctive therapy to primary percutaneous coronary intervention (PCI). ⋯ "Remote ischemic conditioning in ST-elevation myocardial infarction as adjuvant to primary angioplasty" (RIC-STEMI) is an ongoing prospective, single-center, open-label, randomized controlled trial to assess whether RIC as an adjunctive therapy during primary PCI in patients presenting with STEMI can improve clinical outcomes. After enrollment, participants are randomized according to a computer-generated randomization schedule, in a ratio of 1:1 to RIC or no intervention, in blocks of four individuals. RIC is begun at least 10 min before the estimated time of the first balloon inflation and its duration is 30 min. Ischemia is induced by three cycles of inflation of a blood pressure cuff placed on the left lower limb to 200 mmHg and then deflation to 0 mmHg for another 5 min. Primary endpoint is a combined endpoint of death from cardiac cause or hospitalization for heart failure (HF) on follow-up (including device implantation: implantable cardioverter defibrillator, cardiac resynchronization and left ventricular assist device). Secondary endpoints are myocardial infarction (MI) size (estimated by the 48 h area under the curve of serum troponin I levels), development of Q-wave MI, left ventricular function (assessed by echocardiography within the first 3 days after admission), contrast-induced nephropathy, in-hospital mortality, all-cause mortality and, finally, major adverse cardiovascular events. Patients will have a minimum follow-up period of 12 months. From 11 March 2013 to 31 December 2014, 324 patients have been enrolled and randomized. We expect to complete enrollment of the 494 patients deemed necessary within 3 years.
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Randomized controlled trials are considered the "gold standard" for scientific rigor in the assessment of benefits and harms of interventions in healthcare. They may not always be feasible, however, when evaluating quality improvement interventions in real-world healthcare settings. Non-randomized controlled trials (NCTs) are designed to answer questions of effectiveness of interventions in routine clinical practice to inform a decision or process. The on-off NCT design is a relatively new design where participant allocation is by alternation. In alternation, eligible patients are allocated to the intervention "on" or control "off " groups in time series dependent sequential clusters. ⋯ Alternation, as in the on-off design, is a credible form of allocation. The conflict reported by healthcare providers in implementing the design, while not unique to the on-off design, may be alleviated by greater emphasis on the purpose of the research and having research assistants allocate patients and collect data instead of the healthcare providers implementing the trial. In addition, consultation with front-line staff implementing the trials with an on-off design on appropriateness to the setting (e.g., alignment with professional values and the patient population served) may be beneficial.