One-year outcomes of rosuvastatin versus placebo in sepsis-associated acute respiratory distress syndrome: prospective follow-up of SAILS randomised trial

Abstract

Background: Prior randomised trials have evaluated statins in patients with sepsis and acute respiratory distress syndrome (ARDS), but there has been no comprehensive evaluation of long-term effects, despite potential neuromuscular and mental health adverse effects of these drugs.

Aim: To evaluate the effect of rosuvastatin versus placebo on survival, physical function and performance, and mental health outcomes in patients with sepsis-associated ARDS.

Methods: Prospective follow-up evaluation of the ARDS Clinical Trials Network Statins for Acutely Injured Lungs from Sepsis trial of rosuvastatin versus placebo in 568 mechanically ventilated patients with sepsis-associated ARDS, with blinded 6-month outcome assessment performed in the 272 eligible survivors for age-adjusted and sex-adjusted 36-Item Short Form Health Survey (SF-36) physical function and mental health domains, and in 84 eligible survivors for the 6 min walk test, along with secondary outcomes evaluations of survival, and additional patient-reported and performance-based measures at 6-month and 12-month follow-up.

Results: Over 1-year follow-up, there was no significant difference in cumulative survival in the rosuvastatin versus placebo groups (58% vs 61%; p=0.377), with survivors demonstrating substantial impairments in physical function and mental health. Rosuvastatin versus placebo had no effect (mean treatment effect (95% CI)) on SF-36 physical function (0 (-7 to 8), p=0.939) or mental health (-6 (-12 to 1) p=0.085) domains, 6 min walk distance (per cent predicted: 2 (-9 to 14), p=0.679) or the vast majority of secondary outcomes.

Conclusions: Over 1-year follow-up, patients with sepsis-associated ARDS had high cumulative mortality, with survivors commonly experiencing impairments in physical functioning and performance, and mental health. Randomisation to rosuvastatin had no effect on these outcomes.

Trial registration number: NCT00979121 and NCT00719446.

Keywords: ARDS.

Figure 1.. Enrollment and Follow-up

^a Less than the 745 patient sample size of the SAILS trial due to 2 sites not participating in this study and a temporary cessation of recruitment into this study. ^b 8 eligible patients were missed due to temporary cessation of recruitment for ≥7 months for the majority of study sites ^c 4 of these 5 patients were alive at 12 months and 1 was censored for survival analysis ^d 12 of these 12 these patients were alive at 12 months.

Figure 2.. Survival until 12 months after randomization

This figure illustrates the proportion of patients surviving in the study over time for the 568 patients in the ALTOS study cohort, with those who were alive, but excluded from follow-up, censored at hospital discharge. One consenting patient was censored at the 6-month assessment due to loss to follow-up thereafter. Patients who were known to be alive, but missed their 12-month follow-up assessment, were censored at the expected date of their 12-month assessment. The cumulative 1-year survival rate for rosuvastatin vs. placebo was 58% vs. 61% (p=0.377).

Figure 3.. Forest plot – Patient Reported and Performance-Based Physical Outcomes

This figure illustrates the treatment effect for rosuvastatin versus placebo, presented as an effect size, with 95% confidence interval, for the primary outcome (age- and sex-adjusted SF-36 physical function and mental health domains and 6 Minute Walk Test percent predicted) and all secondary outcomes. Effect size was calculated as the treatment effect (Table 3, difference in means or proportions) divided by the pooled standard deviation from the rosuvastatin and placebo groups.^;