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Background: At least a third of patients with a colorectal carcinoma who are candidate for surgery, are anaemic preoperatively. Preoperative anaemia is associated with increased morbidity and mortality. In general practice, little attention is paid to these anaemic patients. Some will have oral iron prescribed others not. The waiting period prior to elective colorectal surgery could be used to optimize a patients' physiological status. The aim of this study is to determine the efficacy of preoperative intravenous iron supplementation in comparison with the standard preoperative oral supplementation in anaemic patients with colorectal cancer. Methods/Design: In this multicentre randomized controlled trial, patients with an M0-staged colorectal carcinoma who are scheduled for curative resection and with a proven iron deficiency anaemia are eligible for inclusion. Main exclusion criteria are palliative surgery, metastatic disease, neoadjuvant chemoradiotherapy (5 × 5 Gy = no exclusion) and the use of Recombinant Human Erythropoietin within three months before inclusion or a blood transfusion within a month before inclusion. Primary endpoint is the percentage of patients that achieve normalisation of the haemoglobin level between the start of the treatment and the day of admission for surgery. This study is a superiority trial, hypothesizing a greater proportion of patients achieving the primary endpoint in favour of iron infusion compared to oral supplementation. A total of 198 patients will be randomized to either ferric(III)carboxymaltose infusion in the intervention arm or ferrofumarate in the control arm. This study will be performed in ten centres nationwide and one centre in Ireland. Discussion: This is the first randomized controlled trial to determine the efficacy of preoperative iron supplementation in exclusively anaemic patients with a colorectal carcinoma. Our trial hypotheses a more profound haemoglobin increase with intravenous iron which may contribute to a superior optimisation of the patient's condition and possibly a decrease in postoperative morbidity. [ABSTRACT FROM AUTHOR]

Background: The use of cardiovascular medication for the primary prevention of cardiovascular disease (CVD) is potentially inappropriate when potential risks outweigh the potential benefits. It is unknown whether deprescribing preventive cardiovascular medication in patients without a strict indication for such medication is safe and cost-effective in general practice., Methods: In this pragmatic cluster randomised controlled non-inferiority trial, we recruited 46 general practices in the Netherlands. Patients aged 40-70 years who were using antihypertensive and/or lipid-lowering drugs without CVD and with low risk of future CVD were followed for 2 years. The intervention was an attempt to deprescribe preventive cardiovascular medication. The primary outcome was the difference in the increase in predicted (10-year) CVD risk in the per-protocol (PP) population with a non-inferiority margin of 2.5 percentage points. An economic evaluation was performed in the intention-to-treat (ITT) population. We used multilevel (generalised) linear regression with multiple imputation of missing data., Results: Of 1067 participants recruited between 7 November 2012 and 18 February 2014, 72% were female. Overall, their mean age was 55 years and their mean predicted CVD risk at baseline was 5%. Of 492 participants in the ITT intervention group, 319 (65%) quit the medication (PP intervention group); 135 (27%) of those participants were still not taking medication after 2 years. The predicted CVD risk increased by 2.0 percentage points in the PP intervention group compared to 1.9 percentage points in the usual care group. The difference of 0.1 (95% CI -0.3 to 0.6) fell within the non-inferiority margin. After 2 years, compared to the usual care group, for the PP intervention group, systolic blood pressure was 6 mmHg higher, diastolic blood pressure was 4 mmHg higher and total cholesterol and low-density lipoprotein-cholesterol levels were both 7 mg/dl higher (all P < 0.05). Cost and quality-adjusted life years did not differ between the groups., Conclusions: The results of the ECSTATIC study show that an attempt to deprescribe preventive cardiovascular medication in low-CVD-risk patients is safe in the short term when blood pressure and cholesterol levels are monitored after stopping. An attempt to deprescribe medication can be considered, taking patient preferences into consideration., Trial Registration: This study was registered with Dutch trial register on 20 June 2012 ( NTR3493 ).

Background: Subcutaneous administration of Ig (SCIg) has gained popularity as an alternative route of administration but has never been rigorously examined in chronic inflammatory demyelinating polyneuropathy (CIDP)., Methods/design: The primary objective of the PATH study (Polyneuropathy and Treatment with Hizentra) is to determine the efficacy of two different doses of SCIg IgPro20 (0.2 g/kg bw or 0.4 g/kg bw) in a 24-week maintenance treatment of CIDP in comparison to placebo. The primary efficacy endpoint will be the proportion of patients who show CIDP relapse (1-point deterioration on the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score) or are withdrawn within 24 weeks after randomization for any reason. IVIg-dependent adult patients with definite or probable CIDP according to the European Federation of Neurological Societies/Peripheral Nerve Society who fulfil the inclusion and exclusion criteria will be eligible. Based on sample-size calculation and relapse assumptions in the three arms, a sample size of 58 is needed per arm (overall sample size will be 350, of which 174 will be randomized). All eligible patients will progress through three study periods: an IgG dependency period (≤12 weeks) to select those who are Ig dependent; an IVIg restabilization period (10 or 13 weeks), which will be performed using the 10 % IgPro10 product; and an SC treatment period (24 weeks, followed by a 1-week completion visit after last follow-up). Patients showing IVIg restabilization will be randomized to demonstrate the efficacy of SCIg IgPro20 maintenance treatment over placebo. After completing the study, subjects are eligible to enter a long-term, open-label, extension study of 1 year or return to their previous treatment. In case of CIDP relapse during the 24-week SC treatment period, IgPro10 rescue medication will be offered. Safety, tolerability, and patients' preference of Ig administration route will be examined., Discussion: The PATH trial, which started in March 2012, is expected to finish at the end of 2016. The results will increase knowledge about the efficacy, safety, and tolerability of SCIg in maintenance management of CIDP patients., Trial Registration: ClinicalTrials.gov, NCT01545076 . Registered on 1 March 2012.

Background: Stroke is a leading cause of death worldwide. Infections after stroke occur in 30% of stroke patients and are strongly associated with unfavourable outcome. Preventive antibiotic therapy lowers infection rate in patients after stroke, however, the effect of preventive antibiotic treatment on functional outcome after stroke has not yet been investigated.The Preventive Antibiotics in Stroke Study (PASS) is an ongoing, multicentre, prospective, randomised, open-label, blinded end point trial of preventive antibiotic therapy in acute stroke. Patients are randomly assigned to either ceftriaxone at a dose of 2 g, given every 24 hours intravenously for four-days, in addition to stroke-unit care, or standard stroke-unit care without preventive antibiotic therapy. Aim of the study is to assess whether preventive antibiotic treatment improves functional outcome at three months by preventing infections., Results: To date, 2,470 patients have been included in PASS. Median stroke severity of the first 2,133 patients (second interim analysis) is 5 (IQR 3 to 9) on the National Institutes of Health Stroke Scale (NIHSS). Due to the PROBE design, no outcome data are available yet. In the initial trial protocol we proposed a dichotomisation of the mRS as primary analysis of outcome and ordinal regression analysis as secondary analysis of primary outcome, requiring a sample size of 3,200 patients. However, ordinal analysis of outcome data is becoming increasingly more common in acute stroke trials, as it increases statistical power. For PASS, funding is insufficient for inclusion of 3,200 patients with the overall inclusion rate of 15 patients per week. Therefore we change the analysis of our primary outcome from dichotomisation to ordinal regression analysis on the mRS. Power analysis showed that with similar assumptions 2,550 patients are needed using ordinal regression analysis. We expect to complete follow-up in June 2014. A full statistical analysis plan will be submitted for publication before treatment allocation will be unblinded., Conclusion: The data from PASS will establish whether preventive antibiotic therapy in acute stroke improves functional outcome by preventing infection. In this update, we changed our primary outcome analysis from dichotomisation to ordinal regression analysis., Trial Registration: Current controlled trials; ISRCTN66140176. Date of registration: 6 April 2010.

Background: Annually approximately 100.000 patients undergo a laparotomy in the Netherlands. About 15,000 of these patients will develop an incisional hernia. Both open and laparoscopic surgical repair have been proven to be safe. However, the most effective treatment of incisional hernias remains unclear. This study, the 'INCH-trial', comparing cost-effectiveness of open and laparoscopic incisional hernia repair, is therefore needed., Methods/design: A randomized multi-center clinical trial comparing cost-effectiveness of open and laparoscopic repair of incisional hernias. Patients with a symptomatic incisional hernia, eligible for laparoscopic and open incisional hernia repair. Only surgeons, experienced in both open and laparoscopic incisional hernia repair, will participate in the INCH trial. During incisional hernia repair, a mesh is placed under or on top of the fascia, with a minimal overlap of 5 cm. Primary endpoint is length of hospital stay after an incisional hernia repair. Secondary endpoints are time to full recovery within three months after index surgery, post-operative complications, recurrences, mortality and quality of life.Our hypothesis is that laparoscopic incisional hernia repair comes with a significant shorter hospital stay compared to open incisional hernia repair. A difference of two days is considered significant. One-hunderd-and-thirty-five patients are enrolled in each treatment arm. The economic evaluation will be performed from a societal perspective. Primary outcomes are costs per patient related to time-to-recovery and quality of life.The main goal of the trial is to establish whether laparoscopic incisional hernia repair is superior to conventional open incisional hernia repair in terms of cost-effectiveness. This is measured through length of hospital stay and quality of life. Secondary endpoints are re-operation rate due to post-operative complications or recurrences, mortality and quality of life., Discussion: The difference in time to full recovery between the two treatment strategies is thought to be in favor of laparoscopic incisional hernia repair. Laparoscopic incisional hernia repair is therefore expected to be a more cost-effective approach., Trial Registration: Netherlands Trial register: NTR2808.