Lactulose reduced falls in cirrhosis in a sequential randomised trial

Design

Sequential multiple assignment randomised trial (SMART), 24 weeks, 4 US centres

Population

230 adults with cirrhosis and portal hypertension without prior overt hepatic encephalopathy

Primary outcome

Hierarchical composite of death or transplant, injurious falls, incident encephalopathy and non-injurious falls (win ratio)

Effect

Lactulose then TeleTai-Chi vs usual care: win ratio 2.7 (95% CI 1.3 to 5.5); injurious falls 4% vs 12%

LiveSMART was a 24-week, two-stage sequential multiple assignment randomised trial at four US centres, enrolling 230 adults with cirrhosis and portal hypertension and no previous overt hepatic encephalopathy. In stage 1 (weeks 1 to 12), participants received lactulose or enhanced usual care with nutrition and fall-prevention education. In stage 2 (weeks 13 to 24) they were randomised to remote tai chi or exercise education.

Lactulose followed by tai chi, compared with enhanced usual care, reduced injurious falls (4% against 12%) and non-injurious falls (19% against 32%). Overt encephalopathy (2% against 0%) and death or transplant (0% in both) did not differ. Comparing lactulose users with non-users, injurious falls were 3.5% against 8.5% and non-injurious falls 15.0% against 26.5%, giving a win ratio of 2.3 (95% CI 1.3 to 4.0). The sequence of lactulose then tai chi had a win ratio of 2.7 (95% CI 1.3 to 5.5) for the hierarchical composite outcome.

The trial was short, with few hard events, and participants had no previous overt encephalopathy. Falls were the measured outcome, not survival, and lactulose's side-effects were not detailed in the abstract.

• Ask about falls at every cirrhosis review, since they are common and consequential
• Consider discussing lactulose with patients with cirrhosis and portal hypertension at high risk of falls, in line with specialist advice
• Pair medication review with strength and balance exercise advice
• Check sedatives, diuretics and antihypertensives that raise fall risk
• Watch for dehydration and electrolyte problems when using lactulose with diuretics

Why it matters

Falls are a leading unmet need for patients with cirrhosis, and few interventions have been tested.

Don't overread it

The trial was 24 weeks long and the benefit was in falls, not in survival; lactulose for primary prevention of encephalopathy is not what it tested.

The statistics, in plain English

A win ratio compares patients pairwise on a ranked list of outcomes, starting with the most important (death or transplant, then injurious falls, encephalopathy and non-injurious falls). A ratio of 2.7 means that, among pairs with a difference, the intervention arm did better 2.7 times as often as it did worse. Only a few patients had the most severe outcomes, so the ratio is driven by falls.

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