lexipafant and Cognition-Disorders

To assess platelet activating factor (PAF) antagonists, potent neuroprotective agents in experimental cerebral dysfunction, in clinical practice.. Double blind, minimised, placebo controlled trial of low and high dose PAF antagonist (lexipafant).. Cardiac surgery unit.. 150 patients undergoing coronary artery bypass graft (CABG) surgery using cardiopulmonary bypass.. Randomisation to placebo, low dose (10 mg) or high dose (100 mg) lexipafant.. Incidence of impairment on four established cognitive tests, undertaken before, five days, and three months after CABG, examined by three methods for defining impairment.. The three groups were similar with respect to preoperative and intraoperative factors. Observed levels of cognitive impairment were less than had been predicted from previous studies. There was no difference in the groups in cognitive change scores at five days or three months. Group mean analysis showed significant time factors for all four tests but not for interactions or for the lexipafant group. A composite cognitive index, based on the aggregate of four normally distributed tests, showed a significant effect for timing of the test but not for the lexipafant group or interaction. Age, but not duration of bypass, was the most important determinant of postoperative cognitive impairment.. The neuroprotective PAF antagonist lexipafant did not differentially reduce the level of cognitive impairment after CABG as determined by power estimates derived from published studies. The strongest predictors of cognitive impairment were age and timing of the test after operation.

Topics: Cognition Disorders; Coronary Artery Bypass; Double-Blind Method; Female; Humans; Imidazoles; Leucine; Male; Middle Aged; Neuroprotective Agents; Neuropsychological Tests; Platelet Activating Factor

To assess the safety and tolerability of lexipafant in HIV-associated cognitive impairment.. Cognitive impairment is the most common neurologic complication of advanced HIV-1 infection. There is evidence that a variety of inflammatory mediators, including platelet-activating factor (PAF), may contribute to neuronal injury. We hypothesized that lexipafant, a PAF antagonist, might improve cognitive dysfunction in HIV-infected people.. We conducted a randomized, double-blind, placebo-controlled clinical trial to assess the safety and tolerability of lexipafant 500 mg/day. The primary outcome measure for tolerability was the ability to complete the study on the originally assigned dosage of medication. Thirty patients with cognitive impairment were enrolled.. Lexipafant was safe and well tolerated. Ninety-three percent in the placebo group and 88% in the lexipafant group completed the study at the originally assigned dosage. Trends toward improvement were seen in neuropsychological performance, especially verbal memory, in the lexipafant treatment group.. This study shows that lexipafant, the first PAF antagonist used in HIV-associated cognitive impairment, is a safe and well tolerated compound. The observed trends toward improvement in neuropsychological test scores warrant the pursuit of a larger and longer efficacy trial to assess the impact of lexipafant on cognitive performance.

Topics: Adult; Cognition Disorders; Double-Blind Method; Female; HIV; Humans; Imidazoles; Leucine; Male; Middle Aged; Neuropsychological Tests; Platelet Activating Factor