ICTUS Study: International Citicoline Trial on Acute Stroke (ICTUS)

June 19, 2012 updated by: Ferrer Internacional S.A.

Citicoline in the Treatment of Acute Ischemic Stroke. An International Randomized Multicenter Placebo-controlled Study

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

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

2298

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Active
Receives active drug
Drug: Citicoline
1g/12h iv during 3 days and then orally until complete 6 weeks of treatment
Other Names:
  • CDP-choline
Placebo Comparator: Placebo
Receives a placebo
Drug: Placebo
As active drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Total recovery at three months of onset, based on a global test analysis including NIHSS, mRS and Barthel Index
Time Frame: 3 months
3 months

Secondary Outcome Measures

Outcome Measure
Time Frame
mRS at 3 months
Time Frame: 3 months
3 months
Barthel Index at 3 months
Time Frame: 3 months
3 months
Safety and tolerability
Time Frame: 3 months
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ferrer Internacional S.A.

Investigators

  • Study Chair: Antoni Dávalos, MD, PhD, Hospital Universitari Germans Trias i Pujol, Badalona (Spain)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2006

Primary Completion (Actual)

February 1, 2012

Study Completion (Actual)

March 1, 2012

Study Registration Dates

First Submitted

May 30, 2006

First Submitted That Met QC Criteria

May 30, 2006

First Posted (Estimate)

May 31, 2006

Study Record Updates

Last Update Posted (Estimate)

June 20, 2012

Last Update Submitted That Met QC Criteria

June 19, 2012

Last Verified

June 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GF-ICTUS-04

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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