A randomized, placebo-controlled, phase 2 study of the efficacy and safety of droxidopa in patients with intradialytic hypotension.

INTRODUCTION: Intradialytic hypotension (IDH) is the most common complication of hemodialysis (HD), and it plays a significant role in the morbidity and mortality associated with maintenance HD. METHODS: This was a placebo-controlled, parallel-group study evaluating efficacy and safety of droxidopa in improving intradialytic blood pressure (BP) responses in 85 adults with end-stage renal disease (ESRD) and prone to IDH. Following screening and baseline periods, patients received 400 mg or 600 mg droxidopa, or placebo, orally 1 hour before HD for 4 weeks. Primary outcome endpoint was the change between baseline and last 2 treatment weeks in average mean arterial pressure (MAP) during HD. Also assessed were changes from baseline in systolic BP (SBP) and diastolic BP (DBP) during and after HD; number of hypotension-induced interventions and symptoms; and adverse events. RESULTS: Increase in droxidopa intra-HD MAP were not significantly different from placebo, although droxidopa groups showed significant improvements in mean SBP after HD of +4.8 ± 11.6 mm Hg (600-mg) and +3.4 ± 13.1 (400-mg) compared with -4.4 ± 17.9 mm Hg in placebo, and the drop seen in mean nadir SBP pre- to intra-HD was also reduced. Changes in mean DBP pre- and post-HD, changes in mean nadir SBP post-HD, or intra-HD SBP were not significant over the treatment period. HD terminations decreased 5-fold in the 600-mg group and 2-fold in the 400-mg group, whereas the number of discontinuations stayed unchanged in the placebo group. Overall, treatment with 600-mg or 400-mg droxidopa was well tolerated in this population. CONCLUSION: These data suggest that droxidopa may have a role in reducing IDH complications in patients with ESRD on chronic HD.

Perioperative topical bovine thrombin exposure is not associated with hemodialysis graft thrombosis.

Arteriovenous (AV) graft use as hemodialysis access remains highly prevalent, with a consequent high thrombosis rate. The magnitude of this problem requires that all potentially modifiable risk factors for graft thrombosis be thoroughly investigated. During graft surgery, topical bovine thrombin is often administered, which can lead to the development of antibovine thrombin antibodies and subsequent hemostatic changes. A recent study correlated the presence of plasma antibovine thrombin antibodies with graft thrombosis in hemodialysis patients. We therefore hypothesized that perioperative topical bovine thrombin exposure would lead to the development of antibovine thrombin antibodies and graft thrombosis. We screened 314 hemodialysis patients and identified 73 patients who had 74 grafts placed for whom complete data on perioperative topical bovine thrombin exposure and subsequent graft outcomes was available. Sixty-one of these patients were available for retrospective measurement of antibovine thrombin antibodies, antihuman thrombin antibodies, and the thrombin activation markers thrombin activatible fibrinolysis inhibitor (TAFI) and thrombin precursor protein (TpP). In these grafts, there was no significant association between topical bovine thrombin exposure and primary assisted patency (P = 0.37). The presence of antibovine thrombin antibodies (P = 0.13), antihuman thrombin antibodies (P = 0.10), and increased TAFI (P = 0.18) were associated with trends toward reduced primary assisted patency which did not reach significance. There was a correlation between antibovine thrombin antibodies and antihuman thrombin antibodies (r = 0.30, P < 0.0001) and between TAFI and TpP trade mark (r = 0.30, P < 0.0001), but no significant correlation between topical bovine thrombin exposure and elevated levels of antibovine thrombin antibodies, antihuman thrombin antibodies, TAFI or TpP trade mark. We conclude that perioperative topical bovine thrombin exposure is not associated with subsequent graft thrombosis.