Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

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

Gladstone Area Water Board Environmental Monitoring Program : aquatic ecosystem monitoring 2004 : fish and habitat assessment

The sampling offish and assessment ofhabitat at four sites downstream of the Awoonga Dam in the Boyne River was carried out from 25/02/04 to 02/03/04. This survey was initiated primarily to determine fish assemblages present following release of environmental flows from the Awoonga Dam in January and February 2004 and to classify habitat features at sites. Techniques employed allow comparison with previous surveys and were specifically directed at targeting Mugil cephal is (mullet) and Lates calcarifer (barramundi)

Gladstone Area Water Board Environmental Monitoring Program : aquatic ecosystem monitoring 2002, habitat, biota and vegetation assessment

To advance sustainable development and management of water within the Boyne River basin, Queensland Department of Natural Resources and Mines released a Resource Operations Plan (ROP) in July 2003. Partial requirements of the ROP include water quality and aquatic ecosystem monitoring which will be used to assist in determining the impacts of Awoonga Dam and of environmental releases on the habitat and biota downstream of the dam (NR&M, 2003). Aquatic ecosystem monitoring of the Boyne River was undertaken for Gladstone Area Water Board in 2001 and 2002 by the Centre for Environmental Management (CEM), Central Queensland University to meet the environmental and conservational commitments in the Boards strategic plan, to add to the existing Environmental Data Collection and Monitoring Programme (EDCM) and in anticipation of fulfilling requirements of the Resource Operations Plan.This summary report will report on most data collected in 2002 at four sites, within six reaches, downstream of the Awoonga Dam

PAP 2.1/2.2 Burnett Basin regional community water quality networks and rivercare

The Centre for Environmental Management, Central Queensland University was commissioned by BMRG to undertake various components of the work relating to the Water Quality and Rivercare Priority Action Plans (PAP's) for the region (Components A, Band C for PAP2.1 and Component C for PAP 2.2). This report documents information arising from PAP 2.1 and 2.2 : Burnett Basin Regional Community Water Quality Networks and Rivercare

Port Curtis mangrove monitoring programme : [for] Gladstone Port Authority

A mangrove monitoring programme was established to assess the possible impacts of industrial developments on the Calliope River mouth and adjacent mangrove communities and to opportunistically study the effects of a severe hail storm which struck mangroves on the Calliope River in 1994

Port Curtis seagrass monitoring programme [for] Southern Pacific Petroleum (Development), Suncor Energy (Management) /

The development of the Stuart Oil Shale project has the capacity to cause indirect and direct impacts on adjacent extensive seagrass/algal beds through increased sedimentation and changes to freshwater flows. As part of a programme to avoid such impacts, Southern Pacific Petroleum Development has funded biannual and annual monitoring of seagrass communities at the Friend Point (5 stations) and Flying Fox Creek (5 stations) mudflats to assess seagrass composition, cover, biomass and macrobenthic diversity since August 1998

Port Curtis macrobenthic monitoring programme [for] Gladstone Port Authority /

This report provides a preliminary analysis of data for sampling periods up to and including April 2000. Subsequent reports will update the data set with the results of the most recent sampling and provide progressive statistical analyses. The aim of this study is "to quantitively assess whether current or future anthropogenic activities significantly impact fauna and the Port Curtis ecosystem" (WBM, 1993)

Port Curtis mangrove monitoring programme [for] Gladstone Port Authority /

A mangrove monitoring programme was established to assess the possible impacts of industrial developments on the Calliope River mouth and adjacent mangrove communities and to opportunistically study the effects of a severe hail storm which struck mangroves on the Calliope River in 1994