25 research outputs found
Efficacy of halopeRIdol to decrease the burden of Delirium In adult Critically ill patiEnts (EuRIDICE): study protocol for a prospective randomised multi-centre double-blind placebo-controlled clinical trial in the Netherlands
Introduction Delirium in critically ill adults is associated
with prolonged hospital stay, increased mortality and
greater cognitive and functional decline. Current practice
guideline recommendations advocate the use of nonpharmacological strategies to reduce delirium. The
routine use of scheduled haloperidol to treat delirium is
not recommended given a lack of evidence regarding its
ability to resolve delirium nor improve relevant short-term
and longer-term outcomes. This study aims to evaluate
the efficacy and safety of haloperidol for the treatment of
delirium in adult critically ill patients to reduce days spent
with coma or delirium.
Methods and analysis EuRIDICE is a prospective, multicentre, randomised, double-blind, placebo-controlled
trial. Study population consists of adult intensive care
unit (ICU) patients without acute neurological injury who
have delirium based on a positive Intensive Care Delirium
Screening Checklist (ICDSC) or Confusion Assessment
Method for the ICU (CAM-ICU) assessment. Intervention
is intravenous haloperidol 2.5mg (or matching placebo)
every 8 hours, titrated daily based on ICDSC or CAMICU positivity to a maximum of 5mg every 8 hours,
until delirium resolution or ICU discharge. Main study
endpoint is delirium and coma-free days (DCFD) up
to 14 days after randomisation. Secondary endpoints
include (1) 28-day and 1-year mortality, (2) cognitive and
functional performance at 3 and 12 months, (3) patient
and family delirium and ICU experience, (4) psychological
sequelae during and after ICU stay, (4) safety concerns
associated with haloperidol use and (5) cost-effectiveness.
Differences in DCFDs between haloperidol and placebo
group will be analysed using Poisson regression analysis.
Study recruitment started in February 2018 and continues.
Ethics and dissemination The study has been approved
by the Medical Ethics Committee of the Erasmus University
Medical Centre Rotterdam (MEC2017-511) and by the
Institutional Review Boards of the participating sites. Its
results will be disseminated via peer-reviewed publication
and conference presentations
Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19
IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.
Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.
DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).
INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days.
MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes.
RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively).
CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570