Full text the role of citicoline in cognitive impairment. Citicoline in the treatment of acute ischemic stroke. Pdf citicoline in the treatment of acute ischaemic. Under the circumstances of the ictus trial, citicoline is not efficacious in the treatment of moderatetosevere acute ischaemic. Health, general clinical trials usage ischemia drug therapy stroke stroke disease. Formal metaanalysis of trials of citicoline in acute and subacute ischemic stroke shows a. Looking for online definition of ictus or what ictus stands for.
How effective is citicoline for acute ischaemic stroke. Citicoline preclinical and clinical update 20092010 stroke. The citicoline brain injury treatment cobrit trial in patients with traumatic brain injury, a randomized, doubleblind, placebocontrolled, multicenter trial, has investigated the effect of 90 days of citicoline treatment on functional outcome in patients with complicated mild. Citicoline was not efficacious in treatment of moderate tosevere acute ischemic stroke ictus trial. T cells promote experimental cerebral ictus trial investigators. Secades4 1 section of quantitative biology and applied statistics. Generally, patients in the ictus trial had more severe strokes than in the previous studies. The role of citicoline in neuroprotection and neurorepair in.
Background citicoline is approved in some countries for the treatment of acute ischaemic stroke. Citicoline in the treatment of acute ischaemic stroke. Citicoline provides no benefit in acute ischemic stroke. A randomized doseresponse trial of citicoline in acute. Pdf potential efficacy of citicoline as adjunct therapy. Despite some suggestions that citicoline may reduce the rates of death and disability following an ischemic stroke, the largest citicoline clinical trial to date, a randomised, placebocontrolled, sequential trial in patients with moderatetosevere acute ischaemic stroke in europe, enrolling 2298 patients, found no benefit of administering.
International citicoline trial on acute stroke ictus. The ictus trial showed that citicoline is not effective in the treatment of moderatetosevere acute ischemic stroke. One of the most recent multicenter studies the ictus trial showed neutral results. Citicoline is the generic name of the pharmaceutical substance that chemically is cytidine5. The drug has shown some evidence of efficacy in a pooled analysis. Cdpcholine has shown neuroprotective effects in cerebral ischemia. Request pdf citicoline in the treatment of acute ischaemic stroke. Cdpcholine and cdp ethanolamine prevent the release of free fatty acids during. Full text current knowledge on the neuroprotective and. Neuroprotective effect of citicoline eye drops on corneal. However, the therapeutic effect of citicoline has been proven to be ineffective in several recent clinical studies on large populations, for instance, the cobrit citicoline brain injury treatment trial, performed on 1,2 patients to treat traumatic brain injury, and the ictus international citicoline trial on acute stroke trial, performed. Citicoline for treating people with acute ischemic stroke marti. The international citicoline trial on acute stroke ictus, which was an.
Listing a study does not mean it has been evaluated by the u. The results of recent citicoline trials by davalos et al. Background and purpose citicoline cytidine59diphosphocholine. A doubleblind, placebocontrolled trial, published by. Neuroprotective strategies for acute ischemic stroke precision and. Data from many preclinical and clinical trials support the hypothesis that citicoline may be a safe and effective treatment for stroke. Labelfree cest mri detection of citicolineliposome drug. Vitor t cruz, jaime masjuan, erik cobo, julio j secades, for the international citicoline trial on acute stroke ictus trial investigators. Background current guidelines recommend an early invasive strategy for patients who have acute coronary syndromes without stsegment elevation and with an elevated cardiac troponin t level. International citicoline trial on acute stroke ictus the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Two recent placebocontrolled trials have demonstrated benefits of citicoline in healthy adults and teens. Because the circumstances of the trial external validity, these results only could. Jul 28, 2012 there is a lack of trials exploring the combined efficacy of citicoline with other neuroprotective drugs that might be investigated in future human studies. The paper gives data available in the literature on the use of citicoline in an experimental model of ischemic stroke is and in randomized multicenter placebocontrolled trials.
This is in contrast to other studies reporting that free cdpcholine at 100 and 250 mg kg was ineffective in tmcao in spraguedawley rats 26,27. A randomized efficacy trial of citicoline in patients with. The ictus trial stated that that administration of citicoline was safe but did not provide evidence that it is efficacious in the treatment of moderatetosevere acute ischemic stroke. The neuroprotective drug citicoline has been extensively studied in clinical trials with volunteers and more than 11,000 patients with various neurologic disorders, including acute ischemic stroke ais. The citicoline brain injury treatment trial cobrit, conducted in united states, is a randomized, doubleblind, placebocontrolled, multicenter trial to analyze the effects of 90 days of citicoline mg twice per day or placebo on functional outcome in patients with complicated mild, moderate, or severe traumatic brain injury. The trial was stopped for futility at the third interim analysis on the basis of complete data from 2078 patients. A hundred patients who suffered from either an ischemic and hemorrhagic stroke and who presented to the hospital within 48 h of stroke onset were enrolled for the study. Cdpcholine may reduce central nervous system ischemic injury by stabilizing cell membranes and reducing free radical generation. Brain sciences free fulltext the role of citicoline. Under the circumstances of the ictus trial, citicoline is not efficacious in the treatment of moderatetosevere acute ischaemic stroke. Odds ratio for good outcome was defined as a modified rankin scale score of 0, 1, or 2. Citicoline, also known as cytidine diphosphatecholine cdpcholine or cytidine 5diphosphocholine is an intermediate in the generation of phosphatidylcholine from choline, a common biochemical process in cell membranes. Reproduced from davalos et al, 29 2012 with permission from elsevier. Specialised register of clinical trials, clinicaltrials.
We postulate that citicoline s neuroprotective effects should need a longer time of administration. Routine clinical use of citicoline in acute ischemic stroke appears to be no longer justified. Citicoline in the treatment of cognitive impairment. Citicoline in stroke and tbi clinical trials nature. We undertook a randomised, placebocontrolled, sequential trial in patients with moderatetosevere acute ischaemic stroke admitted at university hospitals in germany, portugal, and spain. Clinical report by journal of pakistan medical association. The primary analysis will take the form of a global test combining the dichotomized results of assessments on three well. Citicoline repairs cellular membranes and reduces free radicals by. The final randomised analysis was based on data for 2298 patients. In the ictus trial, almost 50% of the patients in both groups received thrombolysis compared with 12.
Ischemic cerebrovascular disease, ictus, citicoline, neuroprotection. The international citicoline trial on acute str oke, ictus 60 was designed to confirm the encouraging results of the data pooling analyses and to repli cate those trends. The primary end point at 90 days was a global recovery test that combined nihss. Feb 07, 2014 citicoline is the generic name of the pharmaceutical substance that chemically is cytidine5. When the ictus results are added to the previous trials of citicoline, the summary effect of citicoline versus placebo on survival free of disability, as measured by an mrs of 0 to 2, was an increase in odds of 14% or 114, 95% ci 100 with a fixed effects model.
A large randomized trial failed to confirm any efficacy of citicoline in improving global recovery after acute ischemic stroke, although a few subgroups appeared to benefit. Citicoline and alzheimers disease ad citicoline may hinder the deposition of betaamyloid, a pivotal neurotoxic protein in the pathophysiology of ad 16. Some other factors could have reduced the sensitivity of the ictus trial eg, poor treatment compliance. Serial plasma choline measurements after cardiac arrest in. It analyzes the results of the ictus trial in which 2298 patients with is who received randomly citicoline or placebo for 24 hours after the onset of symptoms i000 mg intravenously every i2 hours. Cdpcholine liposomes provide significant reduction in. A previous dosecomparison trial in patients with acute stroke found that 500 mg of citicoline appeared to improve neurological outcome with minimal side effects. Table 1 major clinical trials of citicoline in ischemic stroke. Neuroprotective effects of citicoline in tbi questioned. Pdf potential efficacy of citicoline as adjunct therapy in.
Apr, 2016 this study was to evaluate the efficacy and safety of early application of citicoline in the treatment of patients with acute stroke by metaanalysis. Citicoline is a novel neuroprotective agent used in acute. It analyzes the results of the ictus trial in which 2298 patients with is who received randomly citicoline or placebo for 24 hours after the onset of symptoms i000. Free radical generation and downstream oxidative damage. The citicoline brain injury treatment cobrit trial in patients with traumatic brain injury, a randomized, doubleblind, placebocontrolled, multicenter trial, has investigated the effect of 90 days of citicoline treatment on functional outcome in patients with complicated mild, moderate, and severe traumatic brain injury. In any case, the ictus trial has been unable to confirm the efficacy of citicoline. Sep 21, 2012 as the trial was rigorously undertaken and was powered to detect an odds ratio of 1. Ictus is listed in the worlds largest and most authoritative dictionary database of abbreviations and acronyms the free dictionary.
Aug 01, 2014 forest plot for the updated tabulated metaanalysis of clinical citicoline trials. Evaluation of a sequential global test of improved. In humans, although a recent trial international citicoline trial on acute stroke ictus has shown that global recovery is similar in cdpcholine and placebo groups, cdpcholine was shown to be more beneficial in some patients, such as those with moderate stroke severity and not treated with tpa. The citicoline brain injury treatment trial cobrit was a phase iii, doubleblind, randomized, clinical trial conducted between 2007 and 2011 among 1,2 patients at eight us level 1 trauma centers, in order to investigate the effects of citicoline vs placebo in patients with traumatic brain injury tbi, classified as complicated mild. When the ictus results are added to the previous trials of citicoline, the summary effect of citicoline versus placebo on survival free of disability. Citicoline 5002000 mg daily was given to 789 patients with moderateto. Citicoline cdpcholine increases sirtuin1 expression. Randomized controlled trials published until may 2015 were electronically searched in medline, embase, the cochrane central register of controlled trials, who international clinical trial registration platform, clinical trial.
The effects of citicoline on acute ischemic stroke. Early invasive versus selectively invasive management for. Pdf citicoline in the treatment of acute ischaemic stroke. The conclusion is that citicoline is safe to use and may have a bene. May 21, 2011 an international, multicenter, phase iii randomized trial international citicoline trial on acute stroke ictus comparing the efficacy of a 2gram daily dose of citicoline started within 24 hours of ischemic stroke onset and continued for 6 weeks against a placebo is currently ongoing to date. Under the circumstances of the ictus trial, citicoline is not efficacious in the.
Pdf evaluation of a sequential global test of improved. Ictus, international citicoline trial on acute stroke. Brain sciences free fulltext the role of citicoline in. Proceedings of recent developments and future directions in. Rationale for the use of citicoline in the management of. The usbased citicoline brain injury treatment trial cobrit involves 1500 patients with complicated mild, moderate, or severe traumatic brain injury. Also in the ictus trial, it was hypothesized that the bene.
Citicoline, should we continue to indicate it in ischemic cvd. A previous dosecomparison trial in patients with acute stroke found that 500 mg of citicoline appeared to improve neurological outcome with minimal. Ictus was an international, multicenter, prospective, doubleblind, randomized, placebocontrolled trial with participation of neurology services from 37 centers in spain, 11 in. The international citicoline trial on acute stroke, ictus was designed to confirm the encouraging results of the data pooling analyses and to replicate those trends. Citicoline is considered to be a nootropic agent, meaning that it enhances focus, attention, and cognitive function in healthy individuals. Citicoline in the treatment of acute isch malaria by modulating cd8. Secades4 1 section of quantitative biology and applied statistics, school of biological sciences, the. Jul 21, 2008 the primary objective of the trial is to demonstrate improved recovery of patients randomized to citicoline relative to those randomized to placebo after 12 weeks of follow. Studies have investigated a role for citicoline in substance addiction and among patients with bipolar disorder. Evaluation of a sequential global test of improved recovery. Jul 20, 2016 membrane repair and regeneration is necessary for recovery from stroke. Citicoline is the only drug that in a number of different clinical stroke trials continuously had. Three years ago, the results of the ictus trial, made in europe were published, with an overall neutral result because the circumstances of the study 46% patients treated with rtpa, median nihss 15 and bigger infarcts not excluded, concluding that on top of the best treatment possible, citicoline does not show any clinical improvement but. Proceedings of recent developments and future directions.
The international citicoline trial on acute stroke, ictus 60 was. Accordingly, several clinical trials have been carried out to evaluate the effects of cdpcholine in the treatment of cognitive disorders 209. The ictus trial international citicoline trial on acute stroke is being conducted in europe with a maximum of. Citicoline increases phospholipid synthesis and glucose metabolism at brain level, and influences the metabolism of neurotransmitters. Abstract citicoline is a neuroprotectant and neurorestorative drug that is used in the treatment of. Citicoline did not improve functional or cognitive status in patients with traumatic brain injury tbi enrolled in the phase 3 randomized citicoline for brain injury treatment trial cobrit. Furthermore, citicoline may alleviate free fatty acidinduced toxicity which accompanies ischemic insult.
We sought to confirm the efficacy of citicoline in a larger trial. The authors then concluded that the results of the ictus suggested that citicoline might be useful in those patients with acute ischemic stroke who were not treated with rtpa 15. Citicoline is naturally occurring in the cells of human and animal tissue, in particular the organs studies suggest that cdpcholine supplements increase dopamine. Dead this outcome was added for clinical trial purposes and was not part of the original scale. Citicoline is a novel neuroprotective agent used in acute stroke with a significantly favorable outcome. The current trial was a 33center, randomized, doubleblind, efficacy trial in 394 patients comparing placebo n127 with citicoline n267 500 mg po daily for 6 weeks. A single clinical trial ficdpchic, which is a pilot, doubleblind, randomized, placebocontrolled trial, has used citicoline in patients with hemorrhagic stroke.
25 412 641 338 1256 1677 1527 213 1699 172 1788 671 815 49 616 736 1550 988 1536 1508 221 303 229 1257 183 1145 898 737 1150 984