Citicoline in Intracerebral Haemorrhage: A Double-Blind, Randomized, Placebo-Controlled, Multi-Centre Pilot Study

Abstract

Background: In experimental models citicoline has shown beneficial effects in intracerebral haemorrhage. Citicoline is a neuroprotectant drug with some beneficial effects in human ischaemic stroke and with an excellent safety profile. We decided to carry out a pilot study to test its safety and efficacy in human intracerebral haemorrhaging. Methods: In this double-blind, placebo-controlled pilot study, patients had to be previously independent, aged between 40 and 85 years, and had to be admitted within 6 h after onset of symptoms of an acute primary supratentorial hemispheric cerebral haemorrhage diagnosed by neuroimaging (CT or MRI). Baseline severity was defined as patients with a score larger than 8 points on the Glasgow Coma Scale and larger than 7 on the National Institutes of Health Stroke Scale. Patients received either a placebo or 1 g/12 h citicoline for 2 weeks (orally or intravenously). The primary aim was to evaluate safety with respect to the number of adverse events that occurred. The efficacy endpoint was the percentage of patients with a modified Rankin Score (mRS) at 3 months. Results: 19 patients in each group were included in the study. The incidence of serious adverse events was not different among groups (4 patients in each group). One patient in the placebo group was categorised as independent (mRS ≤ 2) in comparison with 5 patients in the citicoline group (OR, 5.38; 95% CI, 0.55–52). Conclusions: Citicoline seems to be a safe drug in human intracerebral haemorrhage with a positive trend regarding efficacy. These data should be confirmed in a larger trial.

Thrombin and hemin as central factors in the mechanisms of intracerebral hemorrhage–induced secondary brain injury and as potential targets for intervention

“…60 Another study involving treatment of 19 patients with citicoline found that treated patients were 5-fold more likely to be functionally independent following ICH compared with those who received a placebo. 110 Finally, a trial of 182 patients revealed that treatment with citicoline resulted in improvement in the Barthel Index, although no effect on the modified Rankin Scale or NIH Stroke Scale was noted.…”

Citicolin in the Treatment of Stroke and Vascular Cognitive Disorders

“…В недавно проведенном в 4 университетских центрах Испании исследовании отмечен положительный эффект цитиколина у больных с кровоизлиянием в головной мозг [20]. В двойное слепое плацебоконтролируемое исследова-ние было включено 38 больных в возрасте 40-85 лет, гос-питализированных в течение 6 ч после развития первично-го кровоизлияния в полушарие головного мозга.…”

“…При кровоизлия-нии в головной мозг возникает дополнительная его ишемия в области прилежащих к гематоме тканей, что определяет целесообразность применения нейропротекторов в остром периоде инсульта. На экспериментальных моделях внутри-мозгового кровоизлияния показано, что при использовании цитиколина наблюдается уменьшение отека головного моз-га и объема зоны ишемии вокруг гематомы [10].В недавно проведенном в 4 университетских центрах Испании исследовании отмечен положительный эффект цитиколина у больных с кровоизлиянием в головной мозг [20]. В двойное слепое плацебоконтролируемое исследова-ние было включено 38 больных в возрасте 40-85 лет, гос-питализированных в течение 6 ч после развития первично-го кровоизлияния в полушарие головного мозга.…”

Effects of celecoxib on volumes of hematoma and edema in patients with primary intracerebral hemorrhage

“…Several drugs have been tested for improving outcome in patients with primary ICH by reducing lesion volumes, but most clinical trials have failed to prove efficacy [7][8][9][10][11][12][13][14]. Previously, we demonstrated that celecoxib, a cyclooxygenase (COX)-2 inhibitor, reduces perihematomal edema, inflammation, and cell death and induces better functional recovery in a rodent model of ICH [15].…”