Lactulose with or without TeleTai-Chi for the prevention of falls: A sequential multiple assignment randomized controlled trial (LiveSMART)

Abstract

Background: Falls are common and morbid for patients with cirrhosis, and patients have identified reducing fall risk as an unmet need and care priority. Approach: This is a 24-week two-stage Sequential, Multiple Assignment Randomized Trial (SMART) at four centers in Michigan, Pennsylvania, and Texas enrolling 230 adults with cirrhosis and portal hypertension without prior overt hepatic encephalopathy (HE). There were two stages. In stage 1 (weeks 1–12), participants were randomized to lactulose or enhanced usual care (education on nutrition and fall prevention). In Stage 2 (weeks 13–24), participants were randomized to TeleTai-Chi or enhanced usual care (exercise education). We evaluated the effectiveness of lactulose with-or-without TeleTai-Chi. The primary outcome was a hierarchical composite of death or transplantation, injurious falls, incident HE, and non-injurious falls. We used an intention-to-treat win ratio (WR). Results: Lactulose followed by TeleTai-Chi, compared with enhanced usual care, reduced injurious falls (4% vs. 12%) and non-injurious falls (19% vs. 32%), with no differences in overt HE (2% vs. 0%) or death/transplantation (0% vs. 0%). Compared with non-users, lactulose users experienced fewer injurious falls (3.5% vs. 8.5%), non-injurious falls (15.0% vs. 26.5%), and overt HE (1.8% vs. 2.6%), with no difference in death/transplantation or adverse events resulting in a WR 2.3 95%CI(1.3-4.0). Sequential lactulose/TeleTai-Chi reduced the risk of the primary outcome compared with usual care (WR 2.7 95%CI(1.305.5). Conclusion: In patients with cirrhosis and portal hypertension without prior overt HE, lactulose reduced falls and fall-related harms. Sequential lactulose followed by TeleTai-Chi was also superior to enhanced usual care.