ICTUS Study: International Citicoline Trial on Acute Stroke
- Conditions
- Acute StrokeCerebral Infarction
- Interventions
- Drug: Placebo
- Registration Number
- NCT00331890
- Lead Sponsor
- Ferrer Internacional S.A.
- Brief Summary
Citicoline is a safe drug approved in some countries for the treatment of acute ischemic stroke. The drug has shown some evidence of efficacy in a pooled analysis, based on four clinical trials done in USA with oral citicoline.The purpose of the study is confirm the results obtained in the pooled analysis, that is, evidence of efficacy in the treatment of acute ischemic stroke
- Detailed Description
The stroke or brain attack is one of the main health problems in developed countries. It is the third cause for death and the main cause of disability in adults. Cerebral infarction makes up 80 % of all the types of strokes.
After a stroke, different evolutions and outcomes can be observed, and there are several factors that may influence the outcome, such as age, cognitive impairment, and psycho-social factors. The most important prognostic factors for acute ischemic stroke are the volume of the cerebral infarction and the severity of the baseline neurological deficit.
In recent years, stroke has been considered a real medical emergency, and for this reason several clinical trials have been conducted to find effective therapies. Among pharmacological therapies, there are two possible ways to treat ischemic strokes: treatments directed to recanalize the occluded artery, such as thrombolysis, and the neuroprotective drugs.
None of the neuroprotective drugs have attained the international approval for this indication. Among the reasons for the failures obtained with the different drugs tested, we must highlight the problems derived from the toxicity of the drugs and from the evaluation criteria, as well as the therapeutic window used.
To evaluate a drug in the treatment of acute ischemic stroke, one must be very careful when defining the schedule of the clinical trial, and which variable or variables may be considered as primary endpoints. Several endpoints have been used in the different clinical trials developed, although the most used are those referring to the functional status and the degree of disability of the patients, normally set at 3 months after the stroke.
After the onset of an ischemic stroke in the brain, there is a cascade of events that are responsible for neuronal disruption, neuronal membrane breakdown and/or neuronal apoptosis, specifically in the penumbra area. Therapies acting by blocking the ischemic cascade, at least partially, and/or stabilizing neuronal membranes are believed to be beneficial protecting the brain from the progressive effects of ischemia. Among the neuroprotective drugs, there is a new class of drugs, of which the main representative is citicoline. Citicoline monosodium is an exogenous form of CDP-Choline, which is essential for the biosynthesis of membrane phospholipids. The mechanisms of action of citicoline include the stimulation of the biosynthesis of phospholipids of the neuronal membrane, the inhibition of the activity of some phospholipases, the restoration of some enzymatic activities bound to neuronal membranes, and the elevation of brain levels of some catecholamines.
The previous clinical trials performed with citicoline were no conclusive, with some positive results. In all these studies, citicoline was found to have a similar safety profile as compared with placebo.
The variety of outcomes and results of the different trials made it difficult to arrive at a consensus on the efficacy of the drug. That is the reason why a Pooling Data Analysis using updated individual patient data was done, with the main objective to determine the effects of citicoline on the improvement, functional and neurological, of patients with acute ischemic stroke treated with different doses of citicoline for 6 weeks and with a follow-up period of 6 weeks. The results obtained in this Pooling Data Analysis showed that the odds ratio of achieving a complete recovery was 33 % higher in citicoline-treated patients than in placebo-treated patients, with the best response obtained with the dose of 2000 mg/d/6 weeks.
The primary objective of this study is to determine the effects on recovery at 3 months of oral citicoline 2000 mg/d/6 weeks, after 6 weeks of treatment and 6 weeks of follow-up, in patients with moderate-to-severe acute ischemic strokes (baseline NIHSS equal or higher than 8) in comparison with placebo.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 2298
- Male or female, >18 years old
- Patients must be treated within 24 hours of their initial stroke symptoms onset.
- Patients with a measurable focal neurological deficit lasting for a minimum of 60 minutes.
- Patients must have a CT scan and/or conventional MRI compatible with the clinical diagnosis of acute ischemic stroke prior to being randomized.
- Patients must have an acute ischemic stroke referable to the middle cerebral artery territory
- At inclusion, NIHSS score > 7, with at least 2 of these points from sections 5 & 6 (motor)
- Immediately (i.e. minutes) pre-stroke, MRS < 2
- Women of childbearing potential must have a negative pregnancy test prior to enrolment
- Signed informed consent
- Patients in coma: patients having a score of 2 or higher in the items regarding the level of consciousness in the NIHSS (1a)
- CT or conventional MRI evidence of brain tumor, cerebral edema with a clinically significant mass midline shift with compression of the ventricles, brainstem or cerebellar infarction, subarachnoid and/or intracerebral and/or intraventricular hemorrhage
- History of ventricular dysrhythmias, acute myocardial infarction within 72 hours prior to enrolment, unstable angina, decompensated congestive heart failure or any other acute, severe, uncontrollable or sustained cardiovascular condition that, in the Investigator's opinion, may interfere with effective participation in the study
- Previous disorders that may confound the interpretation of the neurological scales
- Drug addiction-related disorders
- Pre existing dementia, when dementia implies a disability, measured as an score of 2 or higher in the previous MRS
- Pre existing medical condition that, in the Investigator's opinion, may interfere with the patient's suitability and participation in the study
- Patients participating in another clinical trial or receiving a non-approved drug (clinical investigational drug) less than 30 days prior to screening
- Patients under current treatment with citicoline
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Receives a placebo Active Citicoline Receives active drug
- Primary Outcome Measures
Name Time Method Total recovery at three months of onset, based on a global test analysis including NIHSS, mRS and Barthel Index 3 months
- Secondary Outcome Measures
Name Time Method mRS at 3 months 3 months Barthel Index at 3 months 3 months Safety and tolerability 3 months
Trial Locations
- Locations (64)
Klinikum AltenburgerLand GmbH
🇩🇪Altenburg, Germany
Universitätsklinikum Erlangen
🇩🇪Erlangen, Germany
Johannes Wesling Klinikum Minden
🇩🇪Minden, Germany
Ernst-Moritz-Arndt-Universität Greifswald
🇩🇪Greifswald, Germany
Klinikum Ingolstadt
🇩🇪Ingolstadt, Germany
Neurologische Klinik Universitatsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Hospital Garcia de Orta
🇵🇹Almada, Portugal
Universitätsklinikum Münster
🇩🇪Münster, Germany
Hospital Sao Marcos
🇵🇹Braga, Portugal
Hospital de Santo Antonio
🇵🇹Porto, Portugal
Centro Hospitalar de Coimbra
🇵🇹Coimbra, Portugal
Hospital de Sao Joao
🇵🇹Porto, Portugal
Hospital Sao Sebastiao
🇵🇹Santa Maria da Feira, Portugal
Centro Hospitalar de Setúbal, EPE
🇵🇹Setúbal, Portugal
Hospital Sao Pedro
🇵🇹Vila Real, Portugal
Hospital Son Dureta
🇪🇸Palma de Mallorca, Baleares, Spain
Hospital de Mataro
🇪🇸Mataro, Barcelona, Spain
Hospital Moises Broggi
🇪🇸Sant Joan Despi, Barcelona, Spain
Hospital Meixoeiro
🇪🇸Vigo, Pontevedra, Spain
Hospital Clinico Universitario de Santiago
🇪🇸Santiago de Compostela, La Coruña, Spain
Hospital de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital de Cruces
🇪🇸Barakaldo, Vizcaya, Spain
Hospital Arnau de Vilanova
🇪🇸Lleida, Spain
Hospital de La Princesa
🇪🇸Madrid, Spain
Hospital Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Hospital Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital de Santa Maria
🇵🇹Lisbon, Portugal
Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Consorci Hospitalari Parc Tauli
🇪🇸Sabadell, Barcelona, Spain
Hospital Sagrat Cor
🇪🇸Barcelona, Spain
Hospital San Pedro de Alcantara
🇪🇸Caceres, Spain
Hospital General de Albacete
🇪🇸Albacete, Spain
Hospital de Basurto
🇪🇸Bilbao, Vizcaya, Spain
Hospital de la Santa Creu I Sant Pau
🇪🇸Barcelona, Spain
Hospital de Leon
🇪🇸Leon, Spain
Hospital General Yague
🇪🇸Burgos, Spain
Hospital Vall d´Hebron
🇪🇸Barcelona, Spain
Hospital de Girona Dr. Josep Trueta
🇪🇸Girona, Spain
Hospital Universitari Arnau de Vilanova
🇪🇸Lleida, Spain
Complejo Hospitalario Xeral Calde
🇪🇸Lugo, Spain
Hospital Marqués de Valdecilla
🇪🇸Santander, Spain
Hospital Virgen Macarena
🇪🇸Sevilla, Spain
Hospital Universitario Nuestra Señora De Valme
🇪🇸Sevilla, Spain
Hospital Clinico Universitario
🇪🇸Valencia, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital Universitario La Fe
🇪🇸Valencia, Spain
Hospital Clínico de Valladolid
🇪🇸Valladolid, Spain
Hospital General Universitario de Valencia
🇪🇸Valencia, Spain
Hospital Universitario
🇪🇸Valladolid, Spain
Hospital Central de Defensa (del Aire)
🇪🇸Madrid, Spain
Universitätsklinikum Leipzig
🇩🇪Leipzig, Germany
Hospital Fernando Fonseca
🇵🇹Amadora - Sintra, Portugal
Centro Hospitalar de Setúbal
🇵🇹Setubal, Portugal
Hospital Universitario de Bellvitge
🇪🇸Hospitalet de Llobregat, Barcelona, Spain
Neurologie EVKB
🇩🇪Bielefeld, Germany
Neurologische Klinik Heinrich-Heine Universität
🇩🇪Dusseldorf, Germany
Klinikum Großhadern der Universität München
🇩🇪München, Germany
Hospital Garcia de Orta, EPE
🇵🇹Almada, Portugal
Hospitais da Universidade Coimbra
🇵🇹Coimbra, Portugal
Universitätsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Hospital de Sao Jose
🇵🇹Lisbon, Portugal