低钠血症诊治策略__培训课件.ppt

Discontinuation was mainly due to Infusion site reactions Other ADRs: hypotension, postural hypotension, pyrexia, hyperkalemia, infusion site thrombosis Prospective, multi-center, randomized centrally, double-blind, placebo controlled Conducted 2 trials to assess reproducibility (SALT-1 SALT-2) Tolvaptan 15mg tab 1 tab PO Daily x 30 days OR PBO Important Patient Population Criteria: Inclusion Etiologies: CHF, cirrhosis or SIADH Exclusion Criteria: Other etiologies Hypovolemic hyponatremia Other cardiac diseases (post-MI, SVT, SBP90) Serum Na 120 mmol/L w/ neurological impairment Poor prognosis not tolerating fluid shifts: short-term survival Tolvaptan, a Selective Oral Vasopressin V2-Receptor Antagonist, for Hyponatremia New England Journal of Medicine 355 (2006): 2099-112 Similar Baseline Characteristics across study groups (except height in SALT-2), Mean baseline Na: ~128 mEq/L Co-Administration/Co-intervention: Fluid restriction was not mandatory; treatment with other agents were not allowed (demeclocycline, lithium, urea) Dose adjustments were made at the discretion of the investigator at Day 4 Drug was administered until day 30, final assessments done at day 37 Values were statistically significant Increases in Na were greater in Tolvaptan group than PBO in both trials and in both stratifications at Day 4 and much more at Day 30 Increases were more rapid (by day 4) and greater (marked hyponatremia) New England Journal of Medicine 355 (2006): 2099-112. Tolvaptan patients reached normal Na levels on day 4 and 30 more than PBO Day 4: SALT-1 (40% vs 13%) SALT-2 (55% vs11%) Day 30: SALT-1 (53% vs 25%) SALT-2 (58% vs25%) Less “marked” hyponatremia Day 4: SALT-1 (13% vs 49%) SALT-2 (10% vs 40%) Day 30: SALT-1 (7% vs 35%) SALT-2 (15% vs 32%) ?not sig SF-12 scores Showed difference in “mental component summary” in “marked hyponatremia” patients, but not overall Vitality, social functioning, calmness, sadness No difference in physical component summary OTHER: Day