Granulocyte colony-stimulating factor in patients with acute ischemic stroke: results of the AX200 for Ischemic Stroke trial.

BACKGROUND AND PURPOSE: Granulocyte colony-stimulating factor (G-CSF; AX200; Filgrastim) is a stroke drug candidate with excellent preclinical evidence for efficacy. A previous phase IIa dose-escalation study suggested potential efficacy in humans. The present large phase IIb trial was powered to detect clinical efficacy in acute ischemic stroke patients. METHODS: G-CSF (135 µg/kg body weight intravenous over 72 hours) was tested against placebo in 328 patients in a multinational, multicenter, randomized, and placebo-controlled trial (NCT00927836; www.clinicaltrial.gov). Main inclusion criteria were ≤9-hour time window after stroke onset, infarct localization in the middle cerebral artery territory, baseline National Institutes of Health Stroke Scale score range of 6 to 22, and baseline diffusion-weighted imaging lesion size ≥15 mL. Primary and secondary end points were the modified Rankin scale score and the National Institutes of Health Stroke Scale score at day 90, respectively. Data were analyzed using a prespecified model that adjusted for age, National Institutes of Health Stroke Scale score at baseline, and initial infarct volume (diffusion-weighted imaging). RESULTS: G-CSF treatment failed to meet the primary and secondary end points of the trial. For additional end points such as mortality, Barthel index, or infarct size at day 30, G-CSF did not show efficacy either. There was, however, a trend for reduced infarct growth in the G-CSF group. G-CSF showed the expected peripheral pharmacokinetic and pharmacodynamic profiles, with a strong increase in leukocytes and monocytes. In parallel, the cytokine profile showed a significant decrease of interleukin-1. CONCLUSIONS: G-CSF, a novel and promising drug candidate with a comprehensive preclinical and clinical package, did not provide any significant benefit with respect to either clinical outcome or imaging biomarkers. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00927836.

[Stroke. Diagnosis and therapeutic management of cerebrovascular disease]. / Ictus. Diagnóstico y tratamiento de las enfermedades cerebrovasculares.

Stroke is the second cause of death and the first cause of disability with an important economical cost. Thrombolysis and stroke units are the major contribution to stroke treatment of the last years changing a nihilist therapeutic attitude towards an active attitude, stroke is a medical emergency. Treatment with rtPA has shown to be effective in the first 3 hours following stroke and the FDA and the European Medical Agency (EMEA) have approved its use. A protocolised management of the acute phase to treat physiological complications is the mainstone of stroke units showing a reduction in mortality and disability. Multiple strategies are under development in order to treat more patients, drugs with a longer therapeutic window, intravenous thrombolysis followed by intrarterial thrombolysis, selection of patients with mismatch with new neuroimaging techniques and neuroprotective therapies. Preventive treatment has also experienced a change due to a better knowledge of the ethiopathogeny, the role of vascular risk factors and the development of new preventive drugs. Knowledge of cerebrovascular diseases is today's clue for the best treatment of our patients.

[Stroke units. Project, development, and outcome at a university hospital]. / Unidades de Ictus. Proyecto, desarrollo y resultados en un Hospital Universitario.

After a brief introduction about what an lctus Word is, the authors describe the project for an lctus Ward at the Dr. Josep Trueta University Hospital in Girona. Afterwards, the authors analyze its development and its results during its existence. The authors conclude that there has been a significant increase in benefits for patients since they have received new therapeutic treatments in a specialized ward, furthermore, both doctors and nurses have had the opportunity to develop new research projects.

[Acute phase of stroke]. / Fase aguda del ictus.

Ictus treatment requires an urgent, coordinated, multidisciplinary effort be carried out. Pharmacological treatment of an acute phase of Ictus is another step in an integrated treatment of our patients. The author will concentrate on the specific pharmacological treatment indicated to care for acute Ictus without dealing with the standard support care nor with the treatment of the most usual complications.