Design and implementation of Pharyngeal electrical Stimulation for early de-cannulation in TRACheotomized (PHAST-TRAC) stroke patients with neurogenic dysphagia: a prospective randomized single-blinded interventional study

Rationale: Ongoing dysphagia in stroke patients weaned from mechanical ventilation often requires long-term tracheotomy to protect the airway from aspiration. In a recently reported single-centre pilot study, a significantly larger proportion (75%) of tracheotomized dysphagic stroke patients regained sufficient control of airway management allowing tracheotomy tube removal (decannulation) 24–72 h after pharyngeal electrical stimulation (PES) compared to controls who received standard therapy over the same time period (20%). Aim: To assess the safety and efficacy of PES in accelerating dysphagia rehabilitation and enabling decannulation of tracheotomized stroke patients. Design: International multi-centre prospective randomized controlled single-blind trial in approximately 126 ICU patients (the 90th percentile of the calculated maximum sample size). Study outcomes: Primary outcome: proportion of stroke patients considered safe for decannulation 24–72 h after PES compared to control patients who do not receive PES. Key secondary outcomes focus on: dysphagia severity, decannulation rates, decannulation rate after a repeat PES treatment in patients persistently dysphagic after an initial PES treatment, stroke severity, duration of ICU-stay, occurrence of adverse events including pneumonia and need for recannulation over 30 days or until hospital discharge (if earlier). Discussion: Dysphagia and related airway complications are reported as one of the main reasons for stroke patients remaining tracheotomized once successfully weaned from ventilation. This study will evaluate if PES can improve airway safety sufficiently enough to allow earlier tracheotomy tube removal

Effect of increased convective clearance by on-line hemodiafiltration on all cause and cardiovascular mortality in chronic hemodialysis patients – the Dutch CONvective TRAnsport STudy (CONTRAST): rationale and design of a randomised controlled trial [ISRCTN38365125]

BACKGROUND: The high incidence of cardiovascular disease in patients with end stage renal disease (ESRD) is related to the accumulation of uremic toxins in the middle and large-middle molecular weight range. As online hemodiafiltration (HDF) removes these molecules more effectively than standard hemodialysis (HD), it has been suggested that online HDF improves survival and cardiovascular outcome. Thus far, no conclusive data of HDF on target organ damage and cardiovascular morbidity and mortality are available. Therefore, the CONvective TRAnsport STudy (CONTRAST) has been initiated. METHODS: CONTRAST is a Dutch multi-center randomised controlled trial. In this trial, approximately 800 chronic hemodialysis patients will be randomised between online HDF and low-flux HD, and followed for three years. The primary endpoint is all cause mortality. The main secondary outcome variables are fatal and non-fatal cardiovascular events. CONCLUSION: The study is designed to provide conclusive evidence whether online HDF leads to a lower mortality and less cardiovascular events as compared to standard HD

Stopping clinical trials because of treatment ineffectiveness: a comparison of a futility design with a method of stochastic curtailment

This paper introduces a simple futility design that allows a comparative clinical trial to be stopped due to lack of effect at any of a series of planned interim analyses. Stopping due to apparent benefit is not permitted. The design is for use when any positive claim should be based on the maximum sample size, for example to allow subgroup analyses or the evaluation of safety or secondary efficacy responses. A final frequentist analysis can be performed that is valid for the type of design employed. Here the design is described and its properties are presented. Its advantages and disadvantages relative to the use of stochastic curtailment are discussed. Copyright (C) 2003 John Wiley Sons, Ltd

The sequential analysis of repeated binary responses: a score test for the case of three time points

In this paper a robust method is developed for the analysis of data consisting of repeated binary observations taken at up to three fixed time points on each subject. The primary objective is to compare outcomes at the last time point, using earlier observations to predict this for subjects with incomplete records. A score test is derived. The method is developed for application to sequential clinical trials, as at interim analyses there will be many incomplete records occurring in non-informative patterns. Motivation for the methodology comes from experience with clinical trials in stroke and head injury, and data from one such trial is used to illustrate the approach. Extensions to more than three time points and to allow for stratification are discussed. Copyright © 2005 John Wiley & Sons, Ltd