Effect of Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Initiation on Organ Support–Free Days in Patients Hospitalized With COVID-19: A Randomized Clinical Trial

Writing Committee for the REMAP-CAP Investigators; Lawler, PR; Derde, LPG; van de Veerdonk, FL; McVerry, BJ; Huang, DT; Berry, LR; Lorenzi, E; van Kimmenade, R; Gommans, F; Vaduganathan, M; Leaf, DE; Baron, RM; Kim, EY; Frankfurter, C; Epelman, S; Kwan, Y; Grieve, R; O'Neill, S; Sadique, Z; Puskarich, M; Marshall, JC; Higgins, AM; Mouncey, PR; Rowan, KM; Al-Beidh, F; Annane, D; Arabi, YM; Au, C; Beane, A; van Bentum-Puijk, W; Bonten, MJM; Bradbury, CA; Brunkhorst, FM; Burrell, A; Buzgau, A; Buxton, M; Cecconi, M; Cheng, AC; Cove, M; Detry, MA; Estcourt, LJ; Ezekowitz, J; Fitzgerald, M; Gattas, D; Godoy, LC; Goossens, H; Haniffa, R; Harrison, DA; Hills, T; Horvat, CM; Ichihara, N; Lamontagne, F; Linstrum, KM; McAuley, DF; McGlothlin, A; McGuinness, SP; McQuilten, Z; Murthy, S; Nichol, AD; Owen, DRJ; Parke, RL; Parker, JC; Pollock, KM; Reyes, LF; Saito, H; Santos, MS; Saunders, CT; Seymour, CW; Shankar-Hari, M; Singh, V; Turgeon, AF; Turner, AM; Zarychanski, R; Green, C; Lewis, RJ; Angus, DC; Berry, S; Gordon, AC; McArthur, CJ; Webb, SA

doi:10.1001/jama.2023.4480

Organ support & nutrition

Effect of Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Initiation on Organ Support–Free Days in Patients Hospitalized With COVID-19: A Randomized Clinical Trial

JAMAPublished 11 Apr 2023Randomised controlled trial

Errata to this article were published (JAMA, 26 Dec 2023 ↗ · 17 Sep 2024 ↗)

Enrollment discontinued on February 25, 2022, due to safety concerns

Read the original article ↗PubMed

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Authors' conclusion

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.

Study context

Population: Hospitalised adults with COVID-19 (critically ill and non-critically ill)679 critically ill analysed
Participants: 257 / 248 / 10 / 264

Comparison: Angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation vs no renin-angiotensin system (RAS) inhibitor
ACE inhibitorn = 257
ARBn = 248
ARB + DMX-200n = 10
Controln = 264reference
Primary endpoint: Organ support-free days (composite of hospital survival and days alive without cardiovascular or respiratory organ support); bayesian cumulative logistic model, OR >1 = improvement
Follow-up: 21 days

Methodological detailsadaptive platform, open-label, bayesian analysis, multicentre (69 sites, 7 countries)

Adaptive platform
Open-label
Bayesian analysis
Multicentre (69 sites, 7 countries)

Primary result

As reported in the abstract

Organ support-free days, critically ill

ACE inhibitor10median · IQR −1–16 · days

ARB8median · IQR −1–17 · days

Control12median · IQR 0–17 · days

Each group vs controlMedian adjusted odds ratio (95% CrI)

ACE inhibitorbayesian CrI; posterior probability of worsening 94.9%

0.77(0.58–1.06)

ARBbayesian CrI; posterior probability of worsening 95.4%

0.76(0.56–1.05)

Further findings

Outcome	ACE inhibitor	ARB	Control
Hospital survival, critically ill	71.9%	70.0%	78.8%

Hospital survival, critically ill — Posterior probability ACE inhibitor worsened hospital survival vs control: 95.3%
Hospital survival, critically ill — Posterior probability ARB worsened hospital survival vs control: 98.1%

Reference

Authors: Writing Committee for the REMAP-CAP Investigators, Lawler PR, Derde LPG, van de Veerdonk FL, McVerry BJ, Huang DT, et al.
All 81 authors
Writing Committee for the REMAP-CAP Investigators, Lawler PR, Derde LPG, van de Veerdonk FL, McVerry BJ, Huang DT, Berry LR, Lorenzi E, van Kimmenade R, Gommans F, Vaduganathan M, Leaf DE, Baron RM, Kim EY, Frankfurter C, Epelman S, Kwan Y, Grieve R, O'Neill S, Sadique Z, Puskarich M, Marshall JC, Higgins AM, Mouncey PR, Rowan KM, Al-Beidh F, Annane D, Arabi YM, Au C, Beane A, van Bentum-Puijk W, Bonten MJM, Bradbury CA, Brunkhorst FM, Burrell A, Buzgau A, Buxton M, Cecconi M, Cheng AC, Cove M, Detry MA, Estcourt LJ, Ezekowitz J, Fitzgerald M, Gattas D, Godoy LC, Goossens H, Haniffa R, Harrison DA, Hills T, Horvat CM, Ichihara N, Lamontagne F, Linstrum KM, McAuley DF, McGlothlin A, McGuinness SP, McQuilten Z, Murthy S, Nichol AD, Owen DRJ, Parke RL, Parker JC, Pollock KM, Reyes LF, Saito H, Santos MS, Saunders CT, Seymour CW, Shankar-Hari M, Singh V, Turgeon AF, Turner AM, Zarychanski R, Green C, Lewis RJ, Angus DC, Berry S, Gordon AC, McArthur CJ, Webb SA
Journal: JAMA
Published: 11 Apr 2023
DOI: 10.1001/jama.2023.4480
PubMed: 37039790
Registration: NCT02735707

Topic: Organ support & nutrition

Comparison

ACE inhibitor or ARB initiation vs no RAS inhibitor (control)

Intervention details

ACE inhibitor: open-label initiation of an ACE inhibitor for up to 10 days
ARB: open-label initiation of an ARB for up to 10 days
ARB + DMX-200: ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor)

Key notes

Enrollment discontinued due to safety concerns

Original publication

Effect of Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Initiation on Organ Support–Free Days in Patients Hospitalized With COVID-19: A Randomized Clinical Trial. JAMA. Published 11 April 2023. doi:10.1001/jama.2023.4480

Read the original article ↗

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