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

A one-pot three component synthesis of b-nitro-a-amino acids and their N-alkyl derivatives

A water-based condensation of glyoxylic acid, nitroalkanes and amines is described, offering a straightforward synthesis of β-nitro-a-amino acids and their AT-alky! derivatives

β-Nitro-α-amino Acids as Latent α,β-Dehydro-α-amino Acid Residues in Solid-Phase Peptide Synthesis

β-Nitro-α-amino acids, that are readily accessible through either the reaction of bromoglycine derivatives with alkyl nitronates or the three-component coupling of amines, nitroalkanes and glyoxalate in aqueous base, are easily converted to the corresp

b-nitro-a-amino acids as latent a,b-dehydro-a-amino acid residues in peptides

Peptides containing α,β-dehydro-α-amino acid residues are readily prepared by incorporating β-nitro-α-amino acids at the corresponding positions, followed by elimination of nitrous acid

Synthesis of NTA 3 -DTDA - A Chelator-Lipid that Promotes Stable Binding of His-Tagged Proteins to Membranes

A six-step reaction sequence is described for the preparation of compound 1 (NTA3-DTDA), a membrane-penetrating and potent chelator that can be incorporated into liposomes and plasma membrane vesicles containing antigens and thus allowing targeted delivery of such assemblies to a variety of cells for the purposes of eliciting anti-tumour responses. Full spectroscopic characterization of this dendritic-type compound as well as certain of its precursors is reported