Landiolol fails to reduce organ failure in patients with septic shock and tachycardia: STRESS-L trial

The STRESS-L randomized clinical trial (RCT) enrolled 126 patients with tachycardia and established septic shock (given norepinephrine treatment for >24 hours). It showed that intravenous administration of landiolol to reduce heart rate to less than 95/min compared with standard care did not significantly reduce organ failure as measured by the mean Sequential Organ Failure Assessment (SOFA) score (8.8 versus 8.1, respectively) in the 14 days after randomization.

Septic shock patients undergo adrenergic stress, which affects inflammatory, immune, cardiac, and metabolic pathways. β-Blockade may attenuate the adverse effects of catecholamine exposure and has been linked with reduced mortality. Landiolol (Rapibloc, AOP Health) is a very short-acting β-blocker and is suggested to be about 8 times more selective for the β1-receptor than esmolol.

Tony Whitehouse, Queen Elizabeth Hospital, Birmingham, United Kingdom, and colleagues aimed to assess the safety and efficacy of landiolol in patients with tachycardia and established septic shock requiring prolonged (more than 24 hours) vasopressor support.

For this purpose, the researchers conducted an open-label, multicenter, randomized trial comprising 126 adults (≥18 years) with tachycardia (heart rate ≥95/min) and established septic shock treated for at least 24 hours with continuous norepinephrine (≥0.1 μg/kg/min) in 40 UK National Health Service ICUs (intensive care units). The trial was terminated early in 2021 due to a signal of possible harm.

Sixty-three patients were randomized to receive standard care and 63 received landiolol infusion. The primary outcome was determined as the means SOFA score from randomization through 14 days. Secondary outcomes were mortality at days 28 and 90 and the number of adverse events in each group.

The study led to the following findings:

• The trial was stopped prematurely on the advice of the independent data monitoring committee because it was unlikely to demonstrate benefit and because of possible harm.
• Of the planned 340 participants, 126 were enrolled (mean age, 55.6 years; 58.7% were male).
• The mean SOFA score in the landiolol group was 8.8 compared with 8.1 in the standard care group.
• Mortality at day 28 after randomization in the landiolol group was 37.1% and 25.4% in the standard care group.
• Mortality at day 90 after randomization was 43.5% in the landiolol group and 28.6% in the standard care group.
• There were no differences in the number of patients having at least one adverse event.

"An infusion of landiolol failed to improve organ function over 14 days in patients with septic shock with tachycardia and treated with norepinephrine for more than 24 hours," the researchers wrote.

"These results do not support landiolol use in the management of patients with tachycardia while receiving norepinephrine undergoing treatment for established septic shock" they concluded.