VITATOPS, the VITAmins TO Prevent Stroke Trial: Rationale and design of a randomised trial of B-vitamin therapy in patients with recent transient ischaemic attack or stroke (NCT00097669) (ISRCTN74743444)

Background Epidemiological studies suggest that raised plasma concentrations of total homocysteine (tHcy) may be a common, causal and treatable risk factor for atherothromboembolic ischaemic stroke, dementia and depression. Although tHcy can be lowered effectively with small doses of folic acid, vitamin B12 and vitamin B6, it is not known whether lowering tHcy, by means of B vitamin therapy, can prevent stroke and other major atherothromboembolic vascular events. Aim To determine whether the addition of B-vitamin supplements (folic acid 2 mg, B6 25 mg, B12 500 μg) to best medical and surgical management will reduce the combined incidence of stroke, myocardial infarction (MI) and vascular death in patients with recent stroke or transient ischaemic attack (TIA) of the brain or eye. Design A prospective, international, multicentre, randomised, double blind, placebo-controlled clinical trial. Setting One hundred and four medical centres in 20 countries on five continents. Subjects Eight thousand (6600 recruited as of 5 January, 2006) patients with recent (7 months) stroke (ischaemic or haemorrhagic) or TIA (brain or eye). Randomisation Randomisation and data collection are performed by means of a central telephone service or secure internet site. Intervention One tablet daily of either placebo or B vitamins (folic acid 2mg, B6 25 mg, B12 500 μg). Primary outcome The composite of stroke, MI or death from any vascular cause, whichever occurs first. Outcome and serious adverse events are adjudicated blinded to treatment allocation. Secondary outcomes TIA, unstable angina, revascularisation procedures, dementia, depression. Statistical power With 8000 patients followed up for a median of 2 years and an annual incidence of the primary outcome of 8% among patients assigned placebo, the study will have at least 80% power to detect a relative reduction of 15% in the incidence of the primary outcome among patients assigned B vitamins (to 6·8%/year), applying a two-tailed level of significance of 5%. Conclusion VITATOPS aims to recruit and follow-up 8000 patients between 1998 and 2008, and provide a reliable estimate of the safety and effectiveness of folic acid, vitamin B12, and vitamin B6 supplementation in reducing recurrent serious vascular events among a wide range of patients with TIA and stroke throughout the world. The VITATOPS Trial Study Grou

Incidence and severity of crucial late effects after allogeneic HSCT for malignancy under the age of 3 years: TBI is what really matters

Younger children are considered to be more vulnerable to late effects (LE), which prompted us to study LE in patients after haematopoietic stem cell transplantation (HSCT) for a haematological malignancy before the age of 3. In this multicentre EBMT study, cumulative incidence (CI) and severity of endocrine LE, central nervous system complications and secondary malignancies at 5, 10, 15 and 20 years of follow-up were assessed. Risk factors (RF) like gender, diagnosis, age at and year of HSCT, TBI- or chemo-conditioning and GVHD were analysed. CI of any LE was 0.30, 0.52, 0.66 and 0.72 at 5, 10, 15 and 20 years after HSCT, respectively. In 25% of the patients, LE were severe at a median follow-up of 10.4 years. In multivariate analysis, only TBI was a RF for having any LE and for thyroid dysfunction and growth disturbance. Female gender was a RF for delayed pubertal development. Some more insight could be gained by descriptive analysis regarding the role of TBI and GVHD on the severity of LE. Although only five selected LE have been studied and median follow-up is relatively short, the incidence and severity of these LE are considerable but not different from what has been found in older children and TBI is the main RF.Bone Marrow Transplantation advance online publication, 27 June 2016; doi:10.1038/bmt.2016.139