losartan-potassium and disufenton-sodium

Treatments for spontaneous intracerebral, thrombolytic-induced and intraventricular hemorrhages (IVH) are still at the preclinical or early clinical investigational stages. There has been some renewed interest in the use of surgical evacuation surgery or thrombolytics to remove hematomas, but these techniques can be used only for specific types of brain bleeding. The STICH (Surgical Trial in Intracerebral Haemorrhage) clinical trials should provide some insight into the potential for such techniques to counteract hematoma-induced damage and subsequently, morbidity and mortality. More recently, clinical trials (ATACH [Antihypertensive Treatment in Acute Cerebral Hemorrhage] and INTERACT [Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial]) have begun testing whether or not regulating blood pressure affects the well-being of hemorrhage patients, but the findings thus far have not conclusively demonstrated a positive result. More promising trials, such as the early stage CHANT (Cerebral Hemorrhagic And NXY-059 Treatment) and the late stage FAST (Factor VIIa for Acute Hemorrhagic Stroke Treatment), have addressed whether or not manipulating oxidative stress and components of the blood coagulation cascade can achieve an improved prognosis following spontaneous hemorrhages. However, CHANT was halted prematurely because although it showed that the spin trap agent NXY-059 was safe, it also demonstrated that the drug was ineffective in treating acute ischemic stroke. In addition, the recombinant activated factor VII FAST trial recently concluded with only modestly positive results. Despite a beneficial effect on the primary end point of reducing hemorrhage volume, controlling the coagulation cascade with recombinant factor VIIa did not decrease the mortality rate. Consequently, Novo Nordisk has abandoned further development of the drug for the treatment of intracerebral hemorrhaging. Even though progress in hemorrhage therapy that successfully reduces the escalating morbidity and mortality rate associated with brain bleeding is slow, perseverance and applied translational drug development will eventually be productive. The urgent need for such therapy becomes more evident in light of concerns related to uncontrolled high blood pressure in the general population, increased use of blood thinners by the elderly (e.g., warfarin) and thrombolytics by acute ischemic stroke patients, respectively. The future of drug development for hemorrhage may requi

Topics: Animals; Antihypertensive Agents; Antioxidants; Benzenesulfonates; Blood Pressure; Cardiovascular Agents; Coagulants; Disease Models, Animal; Drug Design; Enzyme Inhibitors; Erythropoietin; Excitatory Amino Acid Antagonists; Factor VIIa; Hemostasis; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Intracranial Hemorrhages; Oxidative Stress; Signal Transduction; Stroke; Treatment Outcome

Stroke remains one of the most urgent medical problems of our times. The failure of most neuroprotective drugs in clinical trials led to the initiation of the Stroke Therapy Academic Industry Roundtable guidelines. Due to this improvement, the positive clinical trial results with the free radical scavenger NXY-059 (SAINT I) was encouraging. However, the subsequent SAINT II trial did not confirm these results. In this article we critically review the history of preclinical and clinical trials based on experience of NXY-059 development and present recommendations for potential future preclinical and clinical development of neuroprotective stroke therapy.

Topics: Animals; Antioxidants; Benzenesulfonates; Brain; Clinical Trials as Topic; Disease Models, Animal; Drug Evaluation; Erythropoietin; Granulocyte Colony-Stimulating Factor; Humans; Magnetic Resonance Imaging; Neuroprotective Agents; Practice Guidelines as Topic; Stroke