Citicoline in the treatment of acute ischaemic stroke: an international, randomised, multicentre, placebo-controlled study (ICTUS trial) Citicoline for acute ischemic stroke in Mexican hospitals: a retrospective postmarketing analysis. A randomized efficacy trial of citicoline in patients with acute ischemic stroke. [Curative effect of soybean lecithin on cerebral infarction]. Higher Prehospital Priority Level of Stroke Improves Thrombolysis Frequency and Time to Stroke Unit: The Hyper Acute STroke Alarm (HASTA) Study Significant variation in mortality and functional outcome after acute ischaemic stroke between western countries: data from the tinzaparin in acute ischaemic stroke trial (TAIST) Treatment of acute cerebral infarction with a choline precursor in a multicenter double-blind placebo-controlled study. Human Tissue Kallikrein Promoted Activation of the Ipsilesional Sensorimotor Cortex after Acute Cerebral Infarction Evaluating treatments in health care: The instability of a one-legged stool Granulocyte Colony–Stimulating Factor in Patients With Acute Ischemic Stroke: Results of the AX200 for Ischemic Stroke Trial [Comparative aspects of using neuroprotectors in the management of patients with ischemic stroke]. [Clinical observation on effect of tongnao huoluo acupuncture therapy in treating acute cerebral infarction at ultra-early or acute stage]. [Observation of therapeutic effect of Salviae miltiorrhiza and cytosine diphosphate-choline injection on patients with hypertensive cerebral hemorrhage]. Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials The midnight-noon ebb-flow point selection for 30 cases of acute ischemic cerebrovascular diseases. [Influence of neuroprotectors with choline-positive action on the level of brain-injury markers during acute ischemic stroke]. Edaravone - citicoline comparative study in acute ischemic stroke (ECCS-AIS). Assessing the quality of randomized controlled trials: an annotated bibliography of scales and checklists. External validity of randomised controlled trials: “To whom do the results of this trial apply?” A phase III randomized efficacy trial of 2000 mg citicoline in acute ischemic stroke patients NXY-059 for the treatment of acute ischemic stroke.
BACKGROUND Citicoline is approved in some countries for the treatment of acute ischaemic stroke . The drug has shown some evidence of efficacy in a pooled analysis . We sought to confirm the efficacy of citicoline in a larger trial . METHODS We undertook a r and omised , placebo-controlled , sequential trial in patients with moderate-to-severe acute ischaemic stroke admitted at university hospitals in Germany , Portugal , and Spain . Using a central ised minimisation process , patients were r and omly assigned in a 1:1 ratio to receive citicoline or placebo within 24 h after the onset of symptoms ( 1000 mg every 12 h intravenously during the first 3 days and orally thereafter for a total of 6 weeks [ 2 × 500 mg oral tablets given every 12 h ] ) . All study participants were masked . The primary outcome was recovery at 90 days measured by a global test combining three measures of success : National Institutes of Health Stroke Scale ≤1 , modified Rankin score ≤1 , and Barthel Index ≥95 . Safety endpoints included symptomatic intracranial haemorrhage in patients treated with recombinant tissue plasminogen activator , neurological deterioration , and mortality . This trial is registered , NCT00331890 . RESULTS 2298 patients were enrolled into the study from Nov 26 , 2006 , to Oct 27 , 2011 . 37 centres in Spain , 11 in Portugal , and 11 in Germany recruited patients . Of the 2298 patients who gave informed consent and underwent r and omisation , 1148 were assigned to citicoline and 1150 to placebo . The trial was stopped for futility at the third interim analysis on the basis of complete data from 2078 patients . The final r and omised analysis was based on data for 2298 patients : 1148 in citicoline group and 1150 in  placebo group . Global recovery was similar in both groups ( odds ratio 1·03 , 95 % CI 0·86 - 1·25 ; p=0·364 ) . No significant differences were reported in the safety variables nor in the rate of adverse events . INTERPRETATION Under the circumstances of the ICTUS trial , citicoline is not efficacious in the treatment of moderate-to-severe acute ischaemic stroke . FUNDING Ferrer Grupo Some neuroprotective agents have shown benefits in animal models , but disappointing results in humans .  Citicoline is used in several countries as coadjuvant treatment in acute ischemic stroke ( AIS ) patients ; however , there are no retrospective postmarketing surveillances on the experience of citicoline in Mexico . The aim of this study was to evaluate the correlation between citicoline exposure and functional outcome at discharge and at 30 and 90 days post-stroke , in a retrospective case-control design on systematic descriptive data bases from three referral hospitals . Clinical records of 173 consecutively registered patients were analyzed , 86 of whom were treated with citicoline within the first 48 h after AIS and the remaining 87 were untreated , r and omly selected controls matched for age ( + /- 5 years ) , gender and NIHSS ( + /- 1 point ) at hospital admission . Pretreatment conditions were similar between groups . Compared with controls , exposure to citicoline was associated with a significantly lower 30-day mean and median modified Rankin score ( in both , P < 0.05 ) . After paired multivariate analyses ( controlled for NIHSS , age , gender , hospital arrival in < 24 h , thrombolysis and comorbidities ) citicoline was independently associated with a lower 90-day mortality risk ( P = 0.047 ) and with fewer in-hospital complications ( mainly infections and sepsis , P = 0.001 ) . In this observational study , citicoline use was associated with a better functional status and lower rates of short-term mortality , possibly due to fewer in-hospital systemic complications . The putative benefits should be interpreted as clinical associations , since this is not a r and omized , controlled clinical trial BACKGROUND AND PURPOSE Citicoline ( cytidine-5'-diphosphocholine ; CDP-choline ) may reduce central nervous system ischemic injury by stabilizing cell membranes and reducing free radical generation . A previous dose-comparison trial in patients with acute stroke found that 500 mg of citicoline appeared to improve neurological outcome with minimal side effects . METHODS The current trial was a 33-center , r and omized , double-blind , efficacy trial in 394 patients comparing placebo ( n=127 ) with citicoline ( n=267 ) ( 500 mg po daily ) for 6 weeks , with a 6-week posttreatment follow-up period . Patients with acute ( 24 hours ) ischemic strokes clinical ly assessed to be in the middle cerebral artery territory with National Institutes of Health Stroke Scale ( NIHSS ) > or = 5 were enrolled . RESULTS Mean time to treatment was 12 hours , and mean age was 71 for placebo and 70 for citicoline . Although mean baseline NIHSS were similar for both groups , there was a higher percentage of placebo patients with NIHSS < 8 ( 34 % vs 22 % ; P<0.01 ) . The incidence and type of side effects were similar between the groups . The planned primary analysis ( logistic regression : 5 categories Barthel ) failed the proportional odds assumption and was rendered unreliable . There were no between-group differences seen on the planned secondary assessment analyses at 90 days , including the Barthel Index > or = 95 at 12 weeks ( last observation carried forward : placebo 40 % ; citicoline 40 % ) or mortality rate  ( placebo 18 % ; citicoline 17 % ) . However , post hoc analyses in a subgroup of patients with baseline NIHSS > or = 8 found that citicoline-treated patients were more likely to have a full recovery ( Barthel > or = 95 ) : placebo 21 % ; citicoline 33 % ; P=0.05 ; whereas no difference was seen in patients with baseline NIHSS<8 ( placebo 77 % ; citicoline 69 % ; P>0.1 . CONCLUSIONS The results of this study indicate that citicoline was safe but ineffective in improving the outcome of patients with acute ischemic stroke who were enrolled in this trial . Post hoc analyses indicate that there may be a subgroup of patients with moderate to severe strokes who would benefit OBJECTIVE To investigate the clinical curative effect of soybean lecithin on cerebral infa rct ion . METHODS 542 patients with cerebral infa rct ion within 48 h after the onset with the nervous function defect scores of 31 - 35 were divided into 3 groups : basic treatment group , 60 cases , with conventional treatment ; citicoline group , 122 patients , with conventional treatment and citicoline ; and soybean lecithin group , 360 patients , with conventional treatment and soybean lecithin 10 g tid . For all patients , treatment began sometime within 48 hours after the onset . The treatment course lasted 28 days . RESULTS When the course was over , the infa rct volumes in basic group citicoline group , and soybean lecithin group , were 7.6 cm3 + /- 2.9 cm3 , 7.3 cm3 + /- 3.1 cm3 , and 6.4 cm3 + /- 2.7 cm3 respectively ( F = 7.371 , P = 0.0007 ) . The basic group and citicoline group being compared with the soybean group by Dunnett test , t = 4.387 and 3.969 respectively , P < 0.01 . The nervous function defect integral in the 3 groups decreased 14.2 + /- 10.93 , 15.0 + /- 9.0 , and 18.5 + /- 10.9 respectively . Two-way analysis of variance of drug kind and beginning time of treatment showed the value of F in drugs as 6.250 , P = 0.0021 , and value of F in times as 0.9417 , P = 0.4201 . In the order of death , deterioration , no improvement , improvement , significant improvement , and recovery , the Ridit values for the comprehensive curative effect in the 3 groups were 0.4003 , 0.4118 , and 0.54 5 respectively ; chi2 = 27.89 , P < 0.001 . CONCLUSION Soybean lecithin is effective in treatment of acute cerebral infa rct ion . The mechanism may be that soybean lecithin lowers the decrease of brain phospholipid content in brain ischemia Background and Purpose — Early initiated treatment of stroke increases the chances of a good recovery . This r and omized controlled study evaluates how an increased priority level for patients with stroke , from level 2 to 1 , from the Emergency Medical Communication Center influences thrombolysis frequency , time to stroke unit , and whether other medical emergencies reported negative consequences . Methods — Patients aged 18 to 85 years in Stockholm , Sweden , with symptoms of stroke within 6 hours were r and omized from the Emergency Medical Communication Center or emergency medical services to an intervention group , priority level 1 , immediate call of an ambulance , or to a control group with st and ard priority level  ,  that is ,  priority level 2 ( within 30 minutes ) .  Before study start , an educational program on identification of stroke and importance of early initiated treatment was directed to all medical dispatchers and ambulance and emergency department personnel . Results — During 2008 , 942 patients were r and omized of which 53 % ( n=496 ) had a final stroke/transient ischemic attack diagnosis .  Patients in the Emergency Medical Communication Center r and omized intervention group reached the stroke unit 26 minutes earlier than the control group ( P<0.001 ) after the emergency call . Thrombolysis was given to 24 % of the patients in the intervention group compared with 10 % of the control subjects ( P<0.001 ) . The higher priority level showed no negative effect on other critical ill patients requiring priority level 1 prehospital attention . Conclusion — This r and omized study shows negligible harm to other medical emergencies , a significant increase in thrombolysis frequency , and a shorter time to the stroke unit for patients with stroke up grade d to priority level 1 from the Emergency Medical Communication Center and through the acute chain of stroke care Background : The medical care of patients with acute stroke varies considerably between countries . This could lead to measurable differences in mortality and functional outcome . Objective : To compare case mix , clinical management , and functional outcome in stroke between 11 countries . Methods : All 1484 patients from 11 countries who were enrolled into the tinzaparin in acute ischaemic stroke trial ( TAIST ) were included in this sub study . Information collected prospect ively on demographics , risk factors , clinical features , measures of service quality ( for example , admission to a stroke unit ) , and outcome were assessed . Outcomes were adjusted for treatment assignment , case mix , and service relative to the British Isles . Results : Differences in case mix ( mostly minor ) and clinical service ( many of prognostic relevance ) were present between the countries . Significant differences in outcome were present between the countries . When assessed by geographical region , death or dependency were lower in North America ( odds ratio ( OR ) adjusted for treatment group only = 0.52 ( 95 % confidence interval , 0.39 to 0.71 ) and north west Europe ( OR = 0.54 ( 0.37 to 0.78 ) ) relative to the British Isles ; similar reductions were found when adjustments were made for 11 case mix variables and five service quality measures . Similarly , case fatality rates were lower in North America ( OR = 0.44 ( 0.30 to 0.66 ) ) and Sc and inavia ( OR = 0.50 ( 0.33 to 0.74 ) ) relative to the British Isles , whether crude or adjusted for case mix and service quality . Conclusions : Both functional outcome and case fatality vary considerably between countries , even when adjusted for prognostic case mix variables and measures of good stroke care . Differing health care systems and the management of patients with acute stroke may contribute to these findings A multicenter double-blind placebo-controlled study of cytidine 5'-diphosphocholine ( CDP-choline ) was conducted to evaluate possible clinical benefits of the drug in patients with acute , moderate to severe cerebral infa rct ion . The patients included also suffered from moderate to mild disturbances of consciousness , and all were admitted within 14 days of the ictus . Patients were allocated r and omly to treatment with either CDP-choline ( 1,000 mg/day i.v . once daily for 14 days ) or with placebo ( physiological saline ) .  One hundred thirty-three patients received CDP-choline treatment , and 139 received placebo .  The group treated with CDP-choline showed significant improvements in level of consciousness compared with the placebo-treated group , and CDP-choline was an entirely safe treatment Background / Aims : Kallikrein , a serine proteinase , has been reported to have many functions , such as selectively dilating arterioles in the ischemic area and enhancing angiogenesis and neurogenesis . Therefore , it may promote cerebral poststroke reorganization . We observed the effect of human tissue kallikrein on the brain motor activation of acute ischemic stroke patients and evaluated patient condition severity and prognosis . Methods : Forty-four cases suffering from cerebral infa rct ion between 6 and 72 h of onset were r and omly assigned into the kallikrein  group ( n = 24 ) and the control group ( n = 20 ) . The control group was given conventional treatment , whereas the kallikrein group was given both conventional treatment and human tissue kallikrein over the course of 12–14 days . The activation of the sensorimotor cortex ( SMC ) and cerebellum , the affected forefinger strength and the NIHSS scores were evaluated before and after treatment . The MBI and MRS scores were assessed at 30 and 90 days after stroke onset . Results : There were no differences between the two groups in activation volume , patient condition and scores before treatment . After treatment , the ipsilesional SMC activation volume was significantly larger and the increase in the volume was significantly greater in the kallikrein group than in the control group ( p < 0.05 for both ) . The NIHSS score was significantly smaller and the improvement in the score was significantly greater in the kallikrein group after treatment ( p < 0.05 for both ) . Moreover , the MBI scores at 30 days were significantly higher , whereas the MRS scores at 30 days were significantly lower in the kallikrein group than in the control group ( p < 0.05 for both ) . Conclusions : Kallikrein improved neural function effectively and quickly after stroke , and promoting cerebral reorganization might be an important mechanism for kallikrein in the treatment of acute cerebral infa rct ion Background Both scientists and the public routinely refer to r and omized controlled trials ( RCTs ) as being the ' gold st and ard ' of scientific evidence . Although there is no question that placebo-controlled RCTs play a significant role in the evaluation of new pharmaceutical treatments , especially when it is important to rule out placebo effects , they have many inherent limitations which constrain their ability to inform medical decision making . The purpose of this paper is to raise questions about over-reliance on RCTs and to point out an additional perspective for evaluating healthcare evidence , as embodied in the Hill criteria . The arguments presented here are generally relevant to all areas of health care , though mental health applications provide the primary context for this essay . Discussion This article first traces the history of RCTs , and then evaluates five of their major limitations : they often lack external validity , they have the potential for increasing health risk in the general population , they are no less likely to overestimate treatment effects than many other methods , they make a relatively weak contribution to clinical practice , and they are excessively expensive ( leading to several additional vulnerabilities in the quality of evidence produced ) . Next , the nine Hill criteria are presented and discussed as a richer approach to the evaluation of health care treatments . Reliance on these multi-faceted criteria requires more analytical thinking than simply examining RCT data , but will also enhance confidence in the evaluation of novel treatments . Summary Excessive reliance on RCTs tends to stifle funding of other types of research , and publication of other forms of evidence . We call upon our research and clinical colleagues to consider additional methods of evaluating data , such as the Hill criteria . Over-reliance on RCTs is similar to resting all of health care evidence on a one-legged stool Background and Purpose — Granulocyte colony – stimulating factor ( G-CSF ; AX200 ; Filgrastim ) is a stroke drug c and i date with excellent pre clinical evidence for efficacy . A previous phase IIa dose – escalation study suggested potential efficacy in humans . The present large phase IIb trial was powered to detect clinical efficacy in acute ischemic stroke patients . Methods — G-CSF ( 135 µg/kg body weight intravenous over 72 hours ) was tested against placebo in 328 patients in a multinational , multicenter , r and omized , and placebo-controlled trial ( NCT00927836 ; www . clinical trial.gov ) . Main inclusion criteria were ⩽9-hour time window after stroke onset , infa rct localization in the middle cerebral artery territory , baseline National Institutes of Health Stroke Scale score range of 6 to 22 , and baseline diffusion-weighted imaging lesion size ≥15 mL. Primary and secondary end points were the modified Rankin scale score and the National Institutes of Health Stroke Scale score at day 90 , respectively . Data were analyzed using a prespecified model that adjusted for age , National Institutes of Health Stroke Scale score at baseline , and initial infa rct volume ( diffusion-weighted imaging ) . Results — G-CSF treatment failed to meet the primary and secondary end points of the trial . For additional end points such as mortality , Barthel index , or infa rct size at day 30 , G-CSF did not show efficacy either . There was , however , a trend for reduced infa rct growth in the G-CSF group . G-CSF showed the expected peripheral pharmacokinetic and pharmacodynamic profiles , with a strong increase in leukocytes and monocytes . In parallel , the cytokine profile showed a significant decrease of interleukin-1 . Conclusions — G-CSF , a novel and promising drug c and i date with a comprehensive pre clinical and clinical package , did not provide any significant benefit with respect to either clinical outcome or imaging biomarkers . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00927836 Comparative efficacy of neuroprotective preparations : actovegin , cerebrolysin and ceraxon was studied in 73 patients in the most acute phase of ischemic stroke . A control group included 33 patients in the most acute phase of ischemic stroke who received only basic treatment without neuroprotectors .  Patient 's state was assessed with the NIHSS , the original scale of E.I. Gusev and V.I. Skvortsova and the Barthel index .  Ceraxon in daily dosage 2 g and cerebrolysin in daily dosage 10 ml during 10 days after the development of ischemic stroke led to the significantly better regression of neurological symptoms to the 21st day of disease compared to the control group . Barthel index scores did not differ in the groups studied OBJECTIVE To evaluate the efficacy and safety of Tongnao Huoluo acupuncture ( TNHLA ) therapy in treating acute cerebral infa rct ion at ultra-early stage ( within 6 hrs after attack ) or acute stage ( within 6 - 48 hrs after attack ) . METHODS The effect of TNHLA in the two stages was observed separately ( treated group ) and compared with the effect treated with immediate thrombolysis by intravenously given urokinase 12 million units in ultra-early stage or simple body acupuncture in acute stage ( control group ) , and with those treated with intravenous dripping of normal saline ( placebo group ) . In the meantime , all groups treated with low molecular dextran injection for 14 days , cytidine diphosphate choline and entric soluble aspirin for 28 days . RESULTS Effect of TNHLA in the treated group was insignificantly different to that after thrombolysis of the control group in the ultra-early stage , but significantly higher than that of body acupuncture in acute stage . The intracranial hemorrhage rates in the treated , control , and placebo group were 3.3 % , 4.0 % , and 8.0 % respectively . CONCLUSION TNHLA is effective and safe in treating acute cerebral infa rct ion at ultra-early stage or acute stage OBJECTIVE To assess the effect of Salviae miltiorrhiza ( SM ) injection in the treatment of hypertensive cerebral hemorrhage ( HCH ) . METHODS Fifty-one cases ( age 50 - 78 years , 61.2 years on average ) of HCH were r and omly divided into three groups ( SM + cytosine diphosphate-choline ( CDP-C ) group and para-aminomethyl benzoic acid ( PAMBA ) + CDP-C group as treated group , CDP-C group as control group ) to observe the outcome of the clinical treatment , hematoma absorbability and changes of ADP-platelet agglutination rate ( Pag ) , prothrombin time(PT ) and function of the liver and kidney . RESULTS The rate of good result ( GR ) and moderate disability ( MD ) in SM group was 85.71 % with the method of Glasgow outcome score ( GOS ) , others were 47.06 % and 61.54 % separately , they have significant difference , P < 0.05 . Among them , SM group had best result . Compared the rate of hematoma absorbability of SM group with that of PAMBA , CDP-C groups , the difference was significant , P < 0.05 . It did not affect the platelet coagulative function in SM group . CONCLUSION SM injection could effectively improve the condition of patients with HCH , and without any side effect . It is worthwhile to be used in the clinical practice BACKGROUND Malignant infa rct ion of the middle cerebral artery ( MCA ) is associated with an 80 % mortality rate . Non-r and omised studies have suggested that decompressive surgery reduces this mortality without increasing the number of severely disabled survivors . To obtain sufficient data as soon as possible to reliably estimate the effects of decompressive surgery , results from three European r and omised controlled trials ( DECIMAL , DESTINY , HAMLET ) were pooled . The trials were ongoing when the pooled analysis was planned . METHODS Individual data for patients aged between 18 years and 60 years , with space-occupying MCA infa rct ion , included in one of the three trials , and treated within 48 h after stroke onset were pooled for analysis . The protocol was design ed prospect ively when the trials were still recruiting patients and outcomes were defined without knowledge of the results of the individual trials . The primary outcome measure was the score on the modified Rankin scale ( mRS ) at 1 year dichotomised between favourable ( 0 - 4 ) and unfavourable ( 5 and death ) outcome . Secondary outcome measures included case fatality rate at 1 year and a dichotomisation of the mRS between 0 - 3 and 4 to death . Data analysis was done by an independent data monitoring committee . FINDINGS 93 patients were included in the pooled analysis . More patients in the decompressive-surgery group than in the control group had an mRS < or=4 ( 75%vs 24 % ; pooled absolute risk reduction 51 % [ 95 % CI 34 - 69 ] ) , an mRS < or=3 ( 43%vs 21 % ; 23 % [ 5 - 41 ] ) , and survived ( 78%vs 29 % ; 50 % [ 33 - 67 ] ) , indicating numbers needed to treat of two for survival with mRS < or=4 , four for survival with mRS < or=3 , and two for survival irrespective of functional outcome . The effect of surgery was highly consistent across the three trials . INTERPRETATION In patients with malignant MCA infa rct ion , decompressive surgery undertaken within 48 h of stroke onset reduces mortality and increases the number of patients with a favourable functional outcome . The decision to perform decompressive surgery should , however , be made on an individual basis in every patient OBJECTIVE To observe the therapeutic effects of midnight-noon ebb-flow method of selecting acupoints ( MNEFMSA ) for acute ischemic cerebrovascular diseases ( AICD ) and its influence on hemorrheology and on the levels of interleukin-6 ( IL-6 ) , thromboxane B2 ( TXB2 ) and 6-keto-prostagl and in F1alpha ( 6-keto-PGF1alpha ) . METHODS The 90 cases were r and omly divided into 3 groups , each consisting of 30 cases . The drug group was treated mainly by routine medication ; in addition to medication , the affected-channel group was treated by acupuncture at points along the course of the affected channel , and the MNEFMSA group was treated by MNEFMSA . RESULTS The total effective rate of MNEFMSA group , affected-channel group and drug group was 96.67 % , 90 % and 73.33 % respectively . The total effective rate of MNEFMSA group was obviously superior to that of the drug group ( P < 0.01 ) , and cure rate and marked improvement rate were obviously superior to those of the drug group and the affected-channel group ( P < 0.05 or P < 0.01 ) . After treatment , the three groups all got improvements in the hemorheological indexes , of which MNEFMSA group got marked improvements in the whole blood viscosity and erythrocyte deformability rate , significantly different from the other two groups ( P < 0.05 ) . At the early stage of treatment and after treatment , the three groups all had IL-6 , TXB2 and 6-keto-PGF1alpha obviously improved ( P < 0.05 or P < 0.01 ) , of which MNEFMSA group got obvious improvement in 6-keto-PGF1alpha and IL-6 ever since the early stage of the treatment ( P < 0.05 ) . CONCLUSIONS In the treatment of acute ischemic cerebrovascular diseases , MNEFMSA can markedly raise the clinical therapeutic effects by improving the hemorheological indexes , lowering the level of IL-6 , and restoring the dynamic equilibrium between TXB2 and 6-keto-PGF1alpha , so as to promote the recovery of cerebral nervous function Choline-positive neuroprotectors citicoline and choline alfoscerate decreased blood concentration of protein S100 in clinical trial on 52 patients in the first days after acute ischemic stroke . Neuroprotective therapy has also produced stabilization of blood-brain barrier BACKGROUND Two new neuro-protective agents , Edaravone and Citicoline were recently found to be beneficial in acute ischemic stroke ( AIS ) . But there is no study to compare these two agents on same protocol in AIS . This study was aim ed to compare these two neuroprotective agents in AIS . METHODS All patients of age more than 18 years who presented within 24 hours of acute ischemic stroke were r and omly treated with Edaravone ( group E ) , Citicoline ( group C ) or none ( group N ) with other st and ard treatment of AIS . Modified Rankin Scale ( MRS ) and National Institute of Health Stroke Scale ( NIHSS ) were recorded on admission and at 3 months . Analysis was done using Anova t test to find out significant difference in outcome at 3 months . P value of < or = 0.05 was labeled as significant . RESULTS Mean MRS and NIHSS scores at 3 months were lowest in group E ( p = 0.000 ) , suggestive of better outcome in this group . After application of severity scale , 15 patients ( 68.1 % ) in group-E , 14 ( 58.3 % ) in group C and 18 ( 72 % ) in group N had moderate to severe stroke ( NIHSS of more than 10 ) . When the patients of moderate to severe stroke were analyzed separately at 3 months , patients in group E ( mean 4.46 + /- 3.52 ) had significantly ( p = 0.00 ) better outcome in comparison to group C ( mean 10.28 + /- 7.93 ) and group N ( mean 9.38 + /- 6.44 ) . CONCLUSIONS Edaravone was found to be associated with better neurological outcome at 3 months . Citicoline 's role as a neuroprotective agent however remains controversial in acute ischaemic stroke Assessing the quality of r and omized controlled trials ( RCTs ) is important and relatively new . Quality gives us an estimate of the likelihood that the results are a valid estimate of the truth . We present an annotated bibliography of scales and checklists developed to assess quality . Twenty-five scales and nine checklists have been developed to assess quality . The checklists are most useful in providing investigators with guidelines as to what information should be included in reporting RCTs . The scales give readers a quantitative index of the likelihood that the reported methodology and results are free of bias . There are several shortcomings with these scales . Future scale development is likely to be most beneficial if questions common to all trials are assessed , if the scale is easy to use , and if it is developed with sufficient rigor In making treatment decisions , doctors and patients must take into account relevant r and omised controlled trials ( RCTs ) and systematic review s. Relevance depends on external validity ( or generalisability)--ie , whether the results can be reasonably applied to a definable group of patients in a particular clinical setting in routine practice . There is concern among clinicians that external validity is often poor , particularly for some pharmaceutical industry trials , a perception that has led to underuse of treatments that are effective . Yet research ers , funding agencies , ethics committees , the pharmaceutical industry , medical journals , and governmental regulators alike all neglect external validity , leaving clinicians to make judgments . However , reporting of the determinants of external validity in trial publications and systematic review s is usually inadequate . This review discusses those determinants , presents a checklist for clinicians , and makes recommendations for greater consideration of external validity in the design and reporting of RCTs Background : Citicoline may reduce CNS ischemic injury by stabilizing cell membranes and reducing free radical generation . Previous safety and efficacy trials in patients who have had acute strokes suggested that citicoline may improve neurologic outcome with minimal side effects . Objective : To determine the safety and efficacy of citicoline treatment in acute stroke patients . Method : An 118-center , r and omized , double-blind , efficacy trial in 899 patients compared placebo ( n = 446 ) with citicoline ( n = 453 ) ( 1000 mg PO twice a day ) for 6 weeks , with a 6-week post-treatment follow-up period . Patients with acute ( ≤24 hours ) ischemic strokes clinical ly thought to be in the middle cerebral artery territory with NIH Stroke Scale ( NIHSS ) scores ≥8 were enrolled . Results : Mean time to treatment was 13 hours for both groups and mean age was 67 years for those receiving placebo and 68 years for those receiving citicoline  . Mean baseline NIHSS scores were 14.5 for placebo and 13.9 for citicoline ( p = 0.06 ) ; medians were 14 for placebo and 13 for citicoline ( p = 0.04 ) . The incidence and type of side effects were similar between the groups . There were no between-group differences on the planned primary analysis , percent of patients with a ≥7-point NIHSS score change at 90 days ( placebo 51 % , citicoline 52 % ) . There were no between-group differences on the other planned secondary analyses at 90 days , including mortality . However , post hoc analyses using st and ard “ excellent recovery ” measures suggested a possible treatment effect on the modified Rankin 0 or 1 ( last observation carried forward : placebo 20 % , citicoline 26 % ; p = 0.025 ) as well as a global outcome statistic . Conclusions : Citicoline was safe but ineffective in improving the outcome of patients with acute ischemic stroke as measured by the planned analyses . Post hoc analyses suggest that a modest treatment effect may have been seen if more traditional analyses had been used BACKGROUND The free-radical-trapping agent NXY-059 showed promise as a neuroprotectant in the Stroke-Acute Ischemic NXY Treatment I ( SAINT I ) trial , reducing disability when given to patients who had acute ischemic stroke . We sought confirmation of efficacy in a second , larger trial . METHODS We enrolled 3306 patients with acute ischemic stroke in a r and omized , double-blind trial to receive a 72-hour infusion of intravenous NXY-059 or placebo within 6 hours after the onset of stroke symptoms . Our primary end point was the distribution of disability scores on the modified Rankin scale at 90 days . We examined scores on neurologic and activities-of-daily-living scales as secondary end points . We also tested the hypothesis that NXY-059 would reduce alteplase-related intracranial hemorrhages . RESULTS The efficacy analysis was based on 3195 patients . Prognostic factors were well balanced between the treatment groups . Mortality was equal in the two groups , and adverse-event rates were similar . The distribution of scores on the modified Rankin scale did not differ between the group treated with NXY-059 ( 1588 patients ) and the placebo group ( 1607 patients ; P=0.33 by the Cochran-Mantel-Haenszel test ; odds ratio for limiting disability , 0.94 ; 95 % confidence interval [ CI ] , 0.83 to 1.06 ) . Analysis of categorized scores on the modified Rankin scale confirmed the lack of benefit : the odds ratio for trichotomization into modified Rankin scale scores of 0 to 1 versus 2 to 3 versus 4 to 6 was 0.92 ( 95 % CI , 0.80 to 1.06 ) . There was no evidence of efficacy for any of the secondary end points . Among patients treated with alteplase , there was no difference between the NXY-059 group and the placebo group in the frequency of symptomatic or asymptomatic hemorrhage . CONCLUSIONS NXY-059 is ineffective for the treatment of acute ischemic stroke within 6 hours after the onset of symptoms . ( Clinical Trials.gov number , NCT00061022 [ Clinical Trials.gov ] .
BACKGROUND Citicoline is a drug approved for the treatment of acute ischemic stroke .
Although evidence of its efficacy has been reported , recently published results of a large placebo-controlled clinical trial did not show differences .
This study aims to assess whether starting citicoline treatment within 14 days after stroke onset improves the outcome in patients with acute ischemic stroke , as compared with placebo .