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Title: The BRAIN TRIAL: a randomised, placebo controlled trial of a Bradykinin B2 receptor antagonist (Anatibant) in patients with traumatic brain injury
Authors: Shakur, Haleema
Andrews, Peter
Asser, Toomas
Balica, Laura
Boeriu, Cristian
Ciro Quintero, Juan Diego
Dewan, Yashbir
Druwé, Patrick
Fletcher, Olivia
Frost, Chris
Hartzenberg, Bennie
Mejia Mantilla, Jorge
Murillo-Cabezas, Francisco
Pachl, Jan
Ravi, Ramalingam R
Rätsep, Indrek
Sampaio, Cristina
Singh, Manmohan
Svoboda, Petr
Roberts, Ian
metadata.dc.contributor.authoraffiliation: [Shakur,H; Fletcher,O; Frost,V; Roberts,I] Department of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK. [Andrews,P] Department of Anaesthesia, Critical Care & Pain Medicine, University of Edinburgh, Royal Infirmary, Edinburgh, UK. [Asser,T] Department of Neurology and Neurosurgery, University of Tartu, Tartu, Estonia. [Balica,L] Emergency Department, Spitalul Clinic de Urgenţă Bucureşti, Bucharest, Romania. [Boeriu,C] Mobile Emergency Service, Spitalul Clinic Judetean Mureş, Târgu Mureş, Romania. [Ciro Quintero,JD] Department of Critical Care, Clínica las Americas, Medellin, Colombia. Neurology Clinic, Instituto Neurológico de Antioquia Medellin, Colombia. [Dewan,Y] Department of Neurosurgery, Christian Medical College, Ludhiana, Punjab, India. [Druwé,P] Department of Accident and Emergency/Intensive Care, Sint-Vincentiushospital, Antwerp, Belgium. [Hartzenberg,B] Department of Neurosurgery, Tygerberg Academic Hospital, Tygerberg, South Africa. [Mejia Mantilla,J] Department of Intensive Care and Anaesthesia, Fundación Clínica Valle del Lili, Cali, Valle del Cauca, Colombia. [Murillo-Cabezas,F] Department of Emergency and Intensive Care, Hospital Universitario Virgen del Rocio, Seville, Spain. [Pachl,J] Department of Anaesthesiology and CCM, Hospital Královské Vinohrady, Prague, Czech Republic. [Ramalingam,RR] Medical Trust Hospital, Ernakulam, Kerala, India. [Rätsep,I] Department of Postoperative Intensive Care, North Estonian Regional Hospital, Tallinn, Estonia. [Sampaio,C] Laboratório de Farmacología Clínica e Tereapêutica, Faculdade de Medicina de Lisboa, Lisbon, Portugal. [Singh,M] Department of Neurosurgery, All India Institute of Medical Sciences, Neurosciences Centre, Ansari Nagar, New Delhi, India. [Svoboda,P] Research Institute for Special Surgery and Trauma, Moravia, Czech Republic.
Keywords: Traumatismos Encefálicos;Escala de Coma de Glasgow;Humanos;Morbilidad;Mediadores de Inflamación;Efecto Placebo;Quinolinas;Factores de Riesgo
metadata.dc.subject.mesh: Medical Subject Headings::Diseases::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Brain Injuries
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Trauma Severity Indices::Glasgow Coma Scale
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Chemicals and Drugs::Biological Factors::Inflammation Mediators
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidity
Medical Subject Headings::Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Epidemiologic Factors::Effect Modifier, Epidemiologic::Placebo Effect
Medical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::Quinolines
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors
Medical Subject Headings::Named Groups::Persons::Age Groups::Adult
Issue Date: 3-Dec-2009
Publisher: BioMed Central
Citation: Shakur H, Andrews P, Asser T, Balica L, Boeriu C, Quintero JD, et al. The BRAIN TRIAL: a randomised, placebo controlled trial of a Bradykinin B2 receptor antagonist (Anatibant) in patients with traumatic brain injury. Trials. 2009; 10:109
Abstract: BACKGROUND Cerebral oedema is associated with significant neurological damage in patients with traumatic brain injury. Bradykinin is an inflammatory mediator that may contribute to cerebral oedema by increasing the permeability of the blood-brain barrier. We evaluated the safety and effectiveness of the non-peptide bradykinin B2 receptor antagonist Anatibant in the treatment of patients with traumatic brain injury. During the course of the trial, funding was withdrawn by the sponsor. METHODS Adults with traumatic brain injury and a Glasgow Coma Scale score of 12 or less, who had a CT scan showing an intracranial abnormality consistent with trauma, and were within eight hours of their injury were randomly allocated to low, medium or high dose Anatibant or to placebo. Outcomes were Serious Adverse Events (SAE), mortality 15 days following injury and in-hospital morbidity assessed by the Glasgow Coma Scale (GCS), the Disability Rating Scale (DRS) and a modified version of the Oxford Handicap Scale (HIREOS). RESULTS 228 patients out of a planned sample size of 400 patients were randomised. The risk of experiencing one or more SAEs was 26.4% (43/163) in the combined Anatibant treated group, compared to 19.3% (11/57) in the placebo group (relative risk = 1.37; 95% CI 0.76 to 2.46). All cause mortality in the Anatibant treated group was 19% and in the placebo group 15.8% (relative risk 1.20, 95% CI 0.61 to 2.36). The mean GCS at discharge was 12.48 in the Anatibant treated group and 13.0 in the placebo group. Mean DRS was 11.18 Anatibant versus 9.73 placebo, and mean HIREOS was 3.94 Anatibant versus 3.54 placebo. The differences between the mean levels for GCS, DRS and HIREOS in the Anatibant and placebo groups, when adjusted for baseline GCS, showed a non-significant trend for worse outcomes in all three measures. CONCLUSION This trial did not reach the planned sample size of 400 patients and consequently, the study power to detect an increase in the risk of serious adverse events was reduced. This trial provides no reliable evidence of benefit or harm and a larger trial would be needed to establish safety and effectiveness. TRIAL REGISTRATION This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN23625128.
Description: Comparative Study; Journal Article; Randomized Controlled Trial;
metadata.dc.identifier.doi: 10.1186/1745-6215-10-109
ISSN: 1745-6215 (Online)
Appears in Collections:01- Artículos - Hospital Virgen del Rocío

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