ICTUS Study: International Citicoline Trial on Acute Stroke

This study has been terminated.
(With 2078 patients, a statistical stopping boundary has now been crossed)
Sponsor:
Information provided by (Responsible Party):
Ferrer Internacional S.A.
ClinicalTrials.gov Identifier:
NCT00331890
First received: May 30, 2006
Last updated: June 19, 2012
Last verified: June 2012
  Purpose

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


Condition Intervention Phase
Acute Stroke
Cerebral Infarction
Drug: Citicoline
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Citicoline in the Treatment of Acute Ischemic Stroke. An International Randomized Multicenter Placebo-controlled Study

Resource links provided by NLM:


Further study details as provided by Ferrer Internacional S.A.:

Primary Outcome Measures:
  • Total recovery at three months of onset, based on a global test analysis including NIHSS, mRS and Barthel Index [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • mRS at 3 months [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Barthel Index at 3 months [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Safety and tolerability [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Enrollment: 2298
Study Start Date: October 2006
Study Completion Date: March 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Active
Receives active drug
Drug: Citicoline
1g/12h iv during 3 days and then orally until complete 6 weeks of treatment
Other Name: CDP-choline
Placebo Comparator: Placebo
Receives a placebo
Drug: Placebo
As active drug

  Hide Detailed Description

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00331890

  Hide Study Locations
Locations
Germany
Klinikum AltenburgerLand GmbH
Altenburg, Germany, 4600
Neurologie EVKB
Bielefeld, Germany, 33617
Neurologische Klinik Heinrich-Heine Universität
Dusseldorf, Germany, 40225
Universitätsklinikum Erlangen
Erlangen, Germany, 91054
Ernst-Moritz-Arndt-Universität Greifswald
Greifswald, Germany, 17489
Universitätsklinikum Hamburg-Eppendorf
Hamburg, Germany, 20246
Neurologische Klinik Universitatsklinikum Heidelberg
Heidelberg, Germany, 69120
Klinikum Ingolstadt
Ingolstadt, Germany, 85049
Universitätsklinikum Leipzig
Leipzig, Germany, 04103
Johannes Wesling Klinikum Minden
Minden, Germany, 32429
Klinikum Großhadern der Universität München
München, Germany, 81377
Universitätsklinikum Münster
Münster, Germany, 48149
Portugal
Hospital Garcia de Orta
Almada, Portugal
Hospital Garcia de Orta, EPE
Almada, Portugal, 2801-951
Hospital Fernando Fonseca
Amadora - Sintra, Portugal, 2720-276
Hospital Sao Marcos
Braga, Portugal, 4700-308
Hospitais da Universidade Coimbra
Coimbra, Portugal, 3000-075
Centro Hospitalar de Coimbra
Coimbra, Portugal, 3040-324
Hospital de Santa Maria
Lisbon, Portugal, 1649-028
Hospital de Sao Jose
Lisbon, Portugal, 1150-119
Hospital de Sao Joao
Porto, Portugal, 4202-451
Hospital de Santo Antonio
Porto, Portugal, 4099-001
Hospital Sao Sebastiao
Santa Maria da Feira, Portugal, 4520-211
Centro Hospitalar de Setúbal
Setubal, Portugal
Centro Hospitalar de Setúbal, EPE
Setúbal, Portugal, 2910-446
Hospital Sao Pedro
Vila Real, Portugal, 5000-508
Spain
Hospital Son Dureta
Palma de Mallorca, Baleares, Spain, 07014
Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, Spain, 08916
Hospital Universitario de Bellvitge
Hospitalet de Llobregat, Barcelona, Spain, 08907
Hospital de Mataro
Mataro, Barcelona, Spain, 08304
Consorci Hospitalari Parc Tauli
Sabadell, Barcelona, Spain, 08208
Hospital Moises Broggi
Sant Joan Despi, Barcelona, Spain, 08970
Hospital Clinico Universitario de Santiago
Santiago de Compostela, La Coruña, Spain, 15706
Hospital de Navarra
Pamplona, Navarra, Spain, 31060
Hospital Meixoeiro
Vigo, Pontevedra, Spain, 36200
Hospital de Cruces
Barakaldo, Vizcaya, Spain, 48903
Hospital de Basurto
Bilbao, Vizcaya, Spain, 48013
Hospital General de Albacete
Albacete, Spain, 02006
Hospital del Mar
Barcelona, Spain, 08003
Hospital Sagrat Cor
Barcelona, Spain, 08029
Hospital Vall d´Hebron
Barcelona, Spain, 08035
Hospital de la Santa Creu I Sant Pau
Barcelona, Spain, 08025
Hospital General Yague
Burgos, Spain, 09005
Hospital San Pedro de Alcantara
Caceres, Spain, 10003
Hospital de Girona Dr. Josep Trueta
Girona, Spain, 17007
Hospital de Leon
Leon, Spain, 24071
Hospital Arnau de Vilanova
Lleida, Spain
Hospital Universitari Arnau de Vilanova
Lleida, Spain, 25198
Complejo Hospitalario Xeral Calde
Lugo, Spain, 27004
Hospital Clinico San Carlos
Madrid, Spain, 28040
Hospital Universitario Gregorio Marañon
Madrid, Spain, 28007
Hospital Central de Defensa (del Aire)
Madrid, Spain, 28047
Hospital Ramon y Cajal
Madrid, Spain, 28034
Hospital Universitario La Paz
Madrid, Spain, 28046
Hospital de La Princesa
Madrid, Spain, 28006
Hospital Marqués de Valdecilla
Santander, Spain
Hospital Marqués de Valdecilla
Santander, Spain, 39008
Hospital Virgen Macarena
Sevilla, Spain, 41009
Hospital Universitario Nuestra Señora De Valme
Sevilla, Spain, 41014
Hospital Universitario Virgen del Rocio
Sevilla, Spain, 41013
Hospital General Universitario de Valencia
Valencia, Spain, 46014
Hospital Universitario La Fe
Valencia, Spain, 46009
Hospital Clinico Universitario
Valencia, Spain, 46010
Hospital Clínico de Valladolid
Valladolid, Spain, 47005
Hospital Universitario
Valladolid, Spain
Sponsors and Collaborators
Ferrer Internacional S.A.
Investigators
Study Chair: Antoni Dávalos, MD, PhD Hospital Universitari Germans Trias i Pujol, Badalona (Spain)
  More Information

Additional Information:
Publications:
Responsible Party: Ferrer Internacional S.A.
ClinicalTrials.gov Identifier: NCT00331890     History of Changes
Other Study ID Numbers: GF-ICTUS-04
Study First Received: May 30, 2006
Last Updated: June 19, 2012
Health Authority: Spain: Spanish Agency of Medicines
Portugal: National Pharmacy and Medicines Institute
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Ferrer Internacional S.A.:
Neuroprotection
Acute ischemic stroke
Cerebral infarction

Additional relevant MeSH terms:
Cerebral Infarction
Stroke
Infarction
Brain Infarction
Brain Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Ischemia
Pathologic Processes
Necrosis
Cytidine Diphosphate Choline
Nootropic Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 27, 2014