Patients Enrolled in Large Randomized Clinical Trials of Antiplatelet Treatment for Prevention After Transient Ischemic Attack or Ischemic Stroke Are Not Representative of Patients in Clinical Practice: the Netherlands Stroke Survey

Background and Purpose—Many randomized clinical trials have evaluated the benefit of long-term use of antiplatelet drugs in reducing the risk of new vascular events in patients with a recent transient ischemic attack or ischemic stroke. Evidence from these trials forms the basis for national and international guidelines for the management of nearly all such patients in clinical practice. However, abundant and strict enrollment criteria may limit the validity and the applicability of results of randomized clinical trials to clinical practice. We estimated the eligibility for participation in landmark trials of antiplatelet drugs of an unselected group of patients with stroke or transient ischemic attack from a national stroke survey. Methods—Nine hundred seventy-two patients with transient ischemic at

Second IVIg course in Guillain-Barré syndrome patients with poor prognosis (SID-GBS trial): Protocol for a double-blind randomized, placebo-controlled clinical trial

One course of intravenous immunoglobulins (IVIg) of 2 g/kg is standard treatment in Guillain-Barré syndrome (GBS) patients unable to walk independently. Despite treatment some patients recover poorly, in part related to rapid consumption of IVIg, indicating that they may benefit from a second course of IVIg. The aim of the study is to determine whether a second course of IVIg, administered 1 week after start of the first course in patients with GBS and predicted poor outcome improves functional outcome on the GBS disability scale after 4 weeks. Secondary outcome measures include adverse events (AEs), Medical Research Council sumscore and GBS disability score after 8, 12, and 26 weeks, length of hospital and ICU admission, mortality, and changes in serum IgG levels. GBS patients of 12 years and older with a poor prognosis, based on the modified Erasmus GBS outcome score (mEGOS) at 1 week after start of the first IVIg course are eligible for randomization in this double-blind, placebo-controlled (IVIg or albumin) clinical trial. This study will determine if a second course of IVIg administered in the acute phase of the disease is safe, feasible, and effective in patients with GBS and a poor prognosis. This Dutch trial is registered prospectively as NTR 2224 in the Netherlands National Trial Register (NTR) which is the Primary Registry in the WHO Registry Network for the Netherlands

Second intravenous immunoglobulin dose in patients with Guillain-Barré syndrome with poor prognosis (SID-GBS): a double-blind, randomised, placebo-controlled trial

Background: Treatment with one standard dose (2 g/kg) of intravenous immunoglobulin is insufficient in a proportion of patients with severe Guillain-Barré syndrome. Worldwide, around 25% of patients severely affected with the syndrome are given a second intravenous immunoglobulin dose (SID), although it has not been proven effective. We aimed to investigate whether a SID is effective in patients with Guillain-Barré syndrome with a predicted poor outcome. Methods: In this randomised, double-blind, placebo-controlled trial (SID-GBS), we included patients (≥12 years) with Guillain-Barré syndrome admitted to one of 59 participating hospitals in the Netherlands. Patients were included on the first day of standard intravenous immunoglobulin treatment (2 g/kg over 5 days). Only patients with a poor prognosis (score of ≥6) according to the modified Erasmus Guillain-Barré syndrome Outcome Score were randomly assigned, via block randomisation stratified by centre, to SID (2 g/kg over 5 days) or to placebo, 7–9 days after inclusion. Patients, outcome adjudicators, monitors, and the steering committee were masked to treatment allocation. The primary outcome measure was the Guillain-Barré syndrome disability score 4 weeks after inclusion. All patients in whom allocated trial medication was started were included in the modified intention-to-treat analysis. This study is registered with the Netherlands Trial Register, NTR 2224/NL2107. Findings: Between Feb 16, 2010, and June 5, 2018, 327 of 339 patients assessed for eligibility were included. 112 had a poor prognosis. Of those, 93 patients with a poor prognosis were included in the modified intention-to-treat analysis: 49 (53%) received SID and 44 (47%) received placebo. The adjusted common odds ratio for improvement on the Guillain-Barré syndrome disability score at 4 weeks was 1·4 (95% CI 0·6–3·3; p=0·45). Patients given SID had more serious adverse events (35% vs 16% in the first 30 days), including thromboembolic events, than those in the placebo group. Four patients died in the intervention group (13–24 weeks after randomisation). Interpretation: Our study does not provide evidence that patients with Guillain-Barré syndrome with a poor prognosis benefit from a second intravenous immunoglobulin course; moreover, it entails a risk of serious adverse events. Therefore, a second intravenous immunoglobulin course should not be considered for treatment of Guillain-Barre syndrome because of a poor prognosis. The results indicate the need for treatment trials with other immune modulators in patients severely affected by Guillain-Barré syndrome. Funding: Prinses Beatrix Spierfonds and Sanquin Plasma Products