A critical assessment of edaravone acute ischemic stroke efficacy trials: is edaravone an effective neuroprotective therapy?

Abstract

Importance of the field-Edaravone (Radicut®) is a free radical scavenger marketed in Japan by Mitsubishi Tanabe Pharma Corporation to treat acute ischemic stroke (AIS) patients presenting within 24 hours of the attack. Injectable edaravone ampoules (30mg b.i.d, i.v., 14 days) were first approved on May 23, 2001. On January 19th 2010, as a new innovation, the Radicut BAG was approved by the Japanese Ministry of Health and Welfare. Efficacy of edaravone range from large significant clinical improvements to only modest improvements in clinical function measured using standard stroke scales when administered 6-72 hours following an ischemic stroke. With almost 17 years of edaravone clinical experience, a few adverse events including acute renal failure have been noted.What the reader will gain-This is the only article to date to critically review available clinical efficacy and toxicology data published in the literature to ascertain whether edaravone should be further pursued as a candidate for development worldwide. Take home message-Edaravone may a useful neuroprotective agent to treat more than 15 million worldwide victims devastated by stroke annually. Additional clinical studies are necessary to verify the efficacy of edaravone.

Edaravone protects human peripheral blood lymphocytes from γ-irradiation-induced apoptosis and DNA damage

“…Edaravone is a potent and novel synthetic scavenger of free radicals, which inhibits both nonenzymatic lipid peroxidation and the lipoxygenase pathway. Notably, edaravone readily crosses the blood-brain barrier (BBB), which is a major advantage in clinical use (Lapchak 2010). In addition to neutralizing multiple ROS and protecting both neurons and endothelial cells in the neurovascular unit, edaravone also exerts anti-apoptotic and anti-inflammatory actions that contribute to cytoprotection in ischemic stroke (Zhang et al 2005).…”

Free-Radical Scavenger Edaravone Treatment Confers Neuroprotection Against Traumatic Brain Injury in Rats

“…These doses correspond to the most commonly used dose in clinical trials, 30 mg i.v., b.i.d. (Lapchak, 2010), by implementing the body surface normalization method to extrapolate from humans to rats (Regan-Shaw et al, 2008). The 10 h interval between edaravone doses was implemented to correspond to the b.i.d use in clinical trials (Lapchak, 2010).…”

“…Although additional clinical studies are necessary to verify its efficacy for ischemic stroke patients (Lapchak, 2010), edaravone's scavenging properties may make it a good candidate for TBI treatment because of the role of oxidative stress in the pathophysiology of TBI (Petronilho et al, 2010). Recently, edaravone has been tested for its neuroprotective and antioxidative effects on the brain after TBI both in rat models and in patients (Dohi et al, 2006;Dohi et al, 2007;Itoh et al, 2010).…”

Edaravone (Radicut), a free radical scavenger, is a potentially useful addition to thrombolytic therapy in patients with acute ischemic stroke

“…Edaravone (Radicut ® ) is a free radical scavenger marketed as a neurovascular protective agent in Japan by Mitsubishi Tanabe Pharma Corporation (Osaka, Japan) for the treatment of patients with AIS, who present within 24 h of the onset of symptoms (19). Edaravone was approved for the treatment of AIS in Japan in 2001, however, it remains under clinical investigation in various other countries (20).…”