Simvastatin in Critically Ill Patients with Covid-19
Copyright © 2023 Massachusetts Medical Society..
BACKGROUND: The efficacy of simvastatin in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear.
METHODS: In an ongoing international, multifactorial, adaptive platform, randomized, controlled trial, we evaluated simvastatin (80 mg daily) as compared with no statin (control) in critically ill patients with Covid-19 who were not receiving statins at baseline. The primary outcome was respiratory and cardiovascular organ support-free days, assessed on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support through day 21 in survivors; the analyis used a Bayesian hierarchical ordinal model. The adaptive design included prespecified statistical stopping criteria for superiority (>99% posterior probability that the odds ratio was >1) and futility (>95% posterior probability that the odds ratio was <1.2).
RESULTS: Enrollment began on October 28, 2020. On January 8, 2023, enrollment was closed on the basis of a low anticipated likelihood that prespecified stopping criteria would be met as Covid-19 cases decreased. The final analysis included 2684 critically ill patients. The median number of organ support-free days was 11 (interquartile range, -1 to 17) in the simvastatin group and 7 (interquartile range, -1 to 16) in the control group; the posterior median adjusted odds ratio was 1.15 (95% credible interval, 0.98 to 1.34) for simvastatin as compared with control, yielding a 95.9% posterior probability of superiority. At 90 days, the hazard ratio for survival was 1.12 (95% credible interval, 0.95 to 1.32), yielding a 91.9% posterior probability of superiority of simvastatin. The results of secondary analyses were consistent with those of the primary analysis. Serious adverse events, such as elevated levels of liver enzymes and creatine kinase, were reported more frequently with simvastatin than with control.
CONCLUSIONS: Although recruitment was stopped because cases had decreased, among critically ill patients with Covid-19, simvastatin did not meet the prespecified criteria for superiority to control. (REMAP-CAP ClinicalTrials.gov number, NCT02735707.).
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:389 |
|---|---|
| Enthalten in: |
The New England journal of medicine - 389(2023), 25 vom: 21. Dez., Seite 2341-2354 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
REMAP-CAP Investigators [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
AGG2FN16EV |
|---|
| Anmerkungen: |
Date Completed 02.01.2024 Date Revised 19.04.2024 published: Print-Electronic ClinicalTrials.gov: NCT02735707 Citation Status MEDLINE |
|---|
| doi: |
10.1056/NEJMoa2309995 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM363809899 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM363809899 | ||
| 003 | DE-627 | ||
| 005 | 20240419232125.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1056/NEJMoa2309995 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1380.xml |
| 035 | |a (DE-627)NLM363809899 | ||
| 035 | |a (NLM)37888913 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 0 | |a REMAP-CAP Investigators |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Simvastatin in Critically Ill Patients with Covid-19 |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 02.01.2024 | ||
| 500 | |a Date Revised 19.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT02735707 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Massachusetts Medical Society. | ||
| 520 | |a BACKGROUND: The efficacy of simvastatin in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear | ||
| 520 | |a METHODS: In an ongoing international, multifactorial, adaptive platform, randomized, controlled trial, we evaluated simvastatin (80 mg daily) as compared with no statin (control) in critically ill patients with Covid-19 who were not receiving statins at baseline. The primary outcome was respiratory and cardiovascular organ support-free days, assessed on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support through day 21 in survivors; the analyis used a Bayesian hierarchical ordinal model. The adaptive design included prespecified statistical stopping criteria for superiority (>99% posterior probability that the odds ratio was >1) and futility (>95% posterior probability that the odds ratio was <1.2) | ||
| 520 | |a RESULTS: Enrollment began on October 28, 2020. On January 8, 2023, enrollment was closed on the basis of a low anticipated likelihood that prespecified stopping criteria would be met as Covid-19 cases decreased. The final analysis included 2684 critically ill patients. The median number of organ support-free days was 11 (interquartile range, -1 to 17) in the simvastatin group and 7 (interquartile range, -1 to 16) in the control group; the posterior median adjusted odds ratio was 1.15 (95% credible interval, 0.98 to 1.34) for simvastatin as compared with control, yielding a 95.9% posterior probability of superiority. At 90 days, the hazard ratio for survival was 1.12 (95% credible interval, 0.95 to 1.32), yielding a 91.9% posterior probability of superiority of simvastatin. The results of secondary analyses were consistent with those of the primary analysis. Serious adverse events, such as elevated levels of liver enzymes and creatine kinase, were reported more frequently with simvastatin than with control | ||
| 520 | |a CONCLUSIONS: Although recruitment was stopped because cases had decreased, among critically ill patients with Covid-19, simvastatin did not meet the prespecified criteria for superiority to control. (REMAP-CAP ClinicalTrials.gov number, NCT02735707.) | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 7 | |a Hydroxymethylglutaryl-CoA Reductase Inhibitors |2 NLM | |
| 650 | 7 | |a Simvastatin |2 NLM | |
| 650 | 7 | |a AGG2FN16EV |2 NLM | |
| 700 | 1 | |a Hills, Thomas E |e verfasserin |4 aut | |
| 700 | 1 | |a Lorenzi, Elizabeth |e verfasserin |4 aut | |
| 700 | 1 | |a Berry, Lindsay R |e verfasserin |4 aut | |
| 700 | 1 | |a Shyamsundar, Murali |e verfasserin |4 aut | |
| 700 | 1 | |a Al-Beidh, Farah |e verfasserin |4 aut | |
| 700 | 1 | |a Annane, Djillali |e verfasserin |4 aut | |
| 700 | 1 | |a Arabi, Yaseen |e verfasserin |4 aut | |
| 700 | 1 | |a Aryal, Diptesh |e verfasserin |4 aut | |
| 700 | 1 | |a Au, Carly |e verfasserin |4 aut | |
| 700 | 1 | |a Beane, Abigail |e verfasserin |4 aut | |
| 700 | 1 | |a Bhimani, Zahra |e verfasserin |4 aut | |
| 700 | 1 | |a Bonten, Marc |e verfasserin |4 aut | |
| 700 | 1 | |a Bradbury, Charlotte A |e verfasserin |4 aut | |
| 700 | 1 | |a Brunkhorst, Frank M |e verfasserin |4 aut | |
| 700 | 1 | |a Burrell, Aidan |e verfasserin |4 aut | |
| 700 | 1 | |a Buxton, Meredith |e verfasserin |4 aut | |
| 700 | 1 | |a Calfee, Carolyn S |e verfasserin |4 aut | |
| 700 | 1 | |a Cecconi, Maurizio |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Allen C |e verfasserin |4 aut | |
| 700 | 1 | |a Cove, Matthew E |e verfasserin |4 aut | |
| 700 | 1 | |a Detry, Michelle A |e verfasserin |4 aut | |
| 700 | 1 | |a Estcourt, Lise J |e verfasserin |4 aut | |
| 700 | 1 | |a Fitzgerald, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Goligher, Ewan C |e verfasserin |4 aut | |
| 700 | 1 | |a Goossens, Herman |e verfasserin |4 aut | |
| 700 | 1 | |a Green, Cameron |e verfasserin |4 aut | |
| 700 | 1 | |a Haniffa, Rashan |e verfasserin |4 aut | |
| 700 | 1 | |a Harrison, David A |e verfasserin |4 aut | |
| 700 | 1 | |a Hashmi, Madiha |e verfasserin |4 aut | |
| 700 | 1 | |a Higgins, Alisa M |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, David T |e verfasserin |4 aut | |
| 700 | 1 | |a Ichihara, Nao |e verfasserin |4 aut | |
| 700 | 1 | |a Jayakumar, Deva |e verfasserin |4 aut | |
| 700 | 1 | |a Kruger, Peter S |e verfasserin |4 aut | |
| 700 | 1 | |a Lamontagne, François |e verfasserin |4 aut | |
| 700 | 1 | |a Lampro, Lamprini |e verfasserin |4 aut | |
| 700 | 1 | |a Lawler, Patrick R |e verfasserin |4 aut | |
| 700 | 1 | |a Marshall, John C |e verfasserin |4 aut | |
| 700 | 1 | |a Mason, Alexina J |e verfasserin |4 aut | |
| 700 | 1 | |a McGlothlin, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a McGuinness, Shay |e verfasserin |4 aut | |
| 700 | 1 | |a McQuilten, Zoe K |e verfasserin |4 aut | |
| 700 | 1 | |a McVerry, Bryan J |e verfasserin |4 aut | |
| 700 | 1 | |a Mouncey, Paul R |e verfasserin |4 aut | |
| 700 | 1 | |a Murthy, Srinivas |e verfasserin |4 aut | |
| 700 | 1 | |a Neal, Matthew D |e verfasserin |4 aut | |
| 700 | 1 | |a Nichol, Alistair D |e verfasserin |4 aut | |
| 700 | 1 | |a O'Kane, Cecilia M |e verfasserin |4 aut | |
| 700 | 1 | |a Parke, Rachael L |e verfasserin |4 aut | |
| 700 | 1 | |a Parker, Jane C |e verfasserin |4 aut | |
| 700 | 1 | |a Rabindrarajan, Ebenezer |e verfasserin |4 aut | |
| 700 | 1 | |a Reyes, Luis F |e verfasserin |4 aut | |
| 700 | 1 | |a Rowan, Kathryn M |e verfasserin |4 aut | |
| 700 | 1 | |a Saito, Hiroki |e verfasserin |4 aut | |
| 700 | 1 | |a Santos, Marlene |e verfasserin |4 aut | |
| 700 | 1 | |a Saunders, Christina T |e verfasserin |4 aut | |
| 700 | 1 | |a Seymour, Christopher W |e verfasserin |4 aut | |
| 700 | 1 | |a Shankar-Hari, Manu |e verfasserin |4 aut | |
| 700 | 1 | |a Sinha, Pratik |e verfasserin |4 aut | |
| 700 | 1 | |a Thompson, B Taylor |e verfasserin |4 aut | |
| 700 | 1 | |a Turgeon, Alexis F |e verfasserin |4 aut | |
| 700 | 1 | |a Turner, Anne M |e verfasserin |4 aut | |
| 700 | 1 | |a van de Veerdonk, Frank |e verfasserin |4 aut | |
| 700 | 1 | |a Weis, Sebastian |e verfasserin |4 aut | |
| 700 | 1 | |a Young, Ian S |e verfasserin |4 aut | |
| 700 | 1 | |a Zarychanski, Ryan |e verfasserin |4 aut | |
| 700 | 1 | |a Lewis, Roger J |e verfasserin |4 aut | |
| 700 | 1 | |a McArthur, Colin J |e verfasserin |4 aut | |
| 700 | 1 | |a Angus, Derek C |e verfasserin |4 aut | |
| 700 | 1 | |a Berry, Scott M |e verfasserin |4 aut | |
| 700 | 1 | |a Derde, Lennie P G |e verfasserin |4 aut | |
| 700 | 1 | |a Webb, Steve A |e verfasserin |4 aut | |
| 700 | 1 | |a Gordon, Anthony C |e verfasserin |4 aut | |
| 700 | 1 | |a McAuley, Daniel F |e verfasserin |4 aut | |
| 700 | 1 | |a Al-Beidh, Farah |e investigator |4 oth | |
| 700 | 1 | |a Angus, Derek |e investigator |4 oth | |
| 700 | 1 | |a Annane, Djillali |e investigator |4 oth | |
| 700 | 1 | |a Arabi, Yaseen |e investigator |4 oth | |
| 700 | 1 | |a Beane, Abigail |e investigator |4 oth | |
| 700 | 1 | |a Berry, Scott |e investigator |4 oth | |
| 700 | 1 | |a Bhimani, Zahra |e investigator |4 oth | |
| 700 | 1 | |a Bonten, Marc |e investigator |4 oth | |
| 700 | 1 | |a Bradbury, Charlotte |e investigator |4 oth | |
| 700 | 1 | |a Brunkhorst, Frank |e investigator |4 oth | |
| 700 | 1 | |a Burrell, Aidan |e investigator |4 oth | |
| 700 | 1 | |a Buxton, Meredith |e investigator |4 oth | |
| 700 | 1 | |a Cecconi, Maurizio |e investigator |4 oth | |
| 700 | 1 | |a Cheng, Allen |e investigator |4 oth | |
| 700 | 1 | |a Cove, Matthew |e investigator |4 oth | |
| 700 | 1 | |a Derde, Lennie |e investigator |4 oth | |
| 700 | 1 | |a Estcourt, Lise |e investigator |4 oth | |
| 700 | 1 | |a Goossens, Herman |e investigator |4 oth | |
| 700 | 1 | |a Gordon, Anthony |e investigator |4 oth | |
| 700 | 1 | |a Green, Cameron |e investigator |4 oth | |
| 700 | 1 | |a Haniffa, Rashan |e investigator |4 oth | |
| 700 | 1 | |a Hills, Thomas |e investigator |4 oth | |
| 700 | 1 | |a Huang, David |e investigator |4 oth | |
| 700 | 1 | |a Ichihara, Nao |e investigator |4 oth | |
| 700 | 1 | |a Lamontagne, François |e investigator |4 oth | |
| 700 | 1 | |a Lawler, Patrick |e investigator |4 oth | |
| 700 | 1 | |a Marshall, John |e investigator |4 oth | |
| 700 | 1 | |a McArthur, Colin |e investigator |4 oth | |
| 700 | 1 | |a McAuley, Daniel |e investigator |4 oth | |
| 700 | 1 | |a McGuinness, Shay |e investigator |4 oth | |
| 700 | 1 | |a McQuilten, Zoe |e investigator |4 oth | |
| 700 | 1 | |a McVerry, Bryan |e investigator |4 oth | |
| 700 | 1 | |a Mouncey, Paul |e investigator |4 oth | |
| 700 | 1 | |a Murthy, Srinivas |e investigator |4 oth | |
| 700 | 1 | |a Nichol, Alistair |e investigator |4 oth | |
| 700 | 1 | |a Parke, Rachael |e investigator |4 oth | |
| 700 | 1 | |a Parker, Jane |e investigator |4 oth | |
| 700 | 1 | |a Reyes, Luis Felipe |e investigator |4 oth | |
| 700 | 1 | |a Rowan, Kathryn |e investigator |4 oth | |
| 700 | 1 | |a Saito, Hiroki |e investigator |4 oth | |
| 700 | 1 | |a Santos, Marlene |e investigator |4 oth | |
| 700 | 1 | |a Seymour, Christopher |e investigator |4 oth | |
| 700 | 1 | |a Shankar-Hari, Manu |e investigator |4 oth | |
| 700 | 1 | |a Turgeon, Alexis |e investigator |4 oth | |
| 700 | 1 | |a Turner, Anne |e investigator |4 oth | |
| 700 | 1 | |a van de Veerdonk, Frank |e investigator |4 oth | |
| 700 | 1 | |a Webb, Steve |e investigator |4 oth | |
| 700 | 1 | |a Zarychanski, Ryan |e investigator |4 oth | |
| 700 | 1 | |a Beqaj, Besa |e investigator |4 oth | |
| 700 | 1 | |a Campbell, Lewis |e investigator |4 oth | |
| 700 | 1 | |a Forbes, Andrew |e investigator |4 oth | |
| 700 | 1 | |a Gattas, David |e investigator |4 oth | |
| 700 | 1 | |a Heritier, Stephane |e investigator |4 oth | |
| 700 | 1 | |a Kruger, Peter |e investigator |4 oth | |
| 700 | 1 | |a McEldrew, Bec |e investigator |4 oth | |
| 700 | 1 | |a Morpeth, Susan |e investigator |4 oth | |
| 700 | 1 | |a Peake, Sandra |e investigator |4 oth | |
| 700 | 1 | |a Presneill, Jeffrey |e investigator |4 oth | |
| 700 | 1 | |a Reynolds, Claire |e investigator |4 oth | |
| 700 | 1 | |a Saxena, Manoj |e investigator |4 oth | |
| 700 | 1 | |a Seppelt, Ian |e investigator |4 oth | |
| 700 | 1 | |a Singh, Vanessa |e investigator |4 oth | |
| 700 | 1 | |a Trapani, Tony |e investigator |4 oth | |
| 700 | 1 | |a Young, Paul |e investigator |4 oth | |
| 700 | 1 | |a Cuthbertson, Brian |e investigator |4 oth | |
| 700 | 1 | |a Fowler, Rob |e investigator |4 oth | |
| 700 | 1 | |a Manoharan, Venika |e investigator |4 oth | |
| 700 | 1 | |a Aryal, Diptesh |e investigator |4 oth | |
| 700 | 1 | |a Dondrop, Arjen M |e investigator |4 oth | |
| 700 | 1 | |a Hasan, Mohd Shahnaz Bin |e investigator |4 oth | |
| 700 | 1 | |a Hashmi, Madiha |e investigator |4 oth | |
| 700 | 1 | |a Jayakumar, Devachandran |e investigator |4 oth | |
| 700 | 1 | |a Kalla, Ismail |e investigator |4 oth | |
| 700 | 1 | |a Kc, Shirish |e investigator |4 oth | |
| 700 | 1 | |a Murray, Lyle |e investigator |4 oth | |
| 700 | 1 | |a Rashan, Sumayyah |e investigator |4 oth | |
| 700 | 1 | |a Tolppa, Timo |e investigator |4 oth | |
| 700 | 1 | |a Siika, Wangari |e investigator |4 oth | |
| 700 | 1 | |a van Bentum-Puijk, Wilma |e investigator |4 oth | |
| 700 | 1 | |a Ehrmann, Stephan |e investigator |4 oth | |
| 700 | 1 | |a Francois, Bruno |e investigator |4 oth | |
| 700 | 1 | |a Pletz, Mathias |e investigator |4 oth | |
| 700 | 1 | |a Povoa, Pedro |e investigator |4 oth | |
| 700 | 1 | |a Rohde, Gernot |e investigator |4 oth | |
| 700 | 1 | |a Weis, Sebastian |e investigator |4 oth | |
| 700 | 1 | |a Alexander, Brian |e investigator |4 oth | |
| 700 | 1 | |a Basile, Kim |e investigator |4 oth | |
| 700 | 1 | |a Girard, Timothy |e investigator |4 oth | |
| 700 | 1 | |a Horvat, Christopher |e investigator |4 oth | |
| 700 | 1 | |a Linstrum, Kelsey |e investigator |4 oth | |
| 700 | 1 | |a Mayr, Florian |e investigator |4 oth | |
| 700 | 1 | |a Wunderley, Renee |e investigator |4 oth | |
| 700 | 1 | |a Roberts, Tracey |e investigator |4 oth | |
| 700 | 1 | |a Doi, Yohei |e investigator |4 oth | |
| 700 | 1 | |a Fujitani, Shigeki |e investigator |4 oth | |
| 700 | 1 | |a Honda, Hitoshi |e investigator |4 oth | |
| 700 | 1 | |a Jindai, Kazuaki |e investigator |4 oth | |
| 700 | 1 | |a Kamata, Kazuhiro |e investigator |4 oth | |
| 700 | 1 | |a Kato, Hideaki |e investigator |4 oth | |
| 700 | 1 | |a Kunishima, Hiroyuki |e investigator |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |t The New England journal of medicine |d 1945 |g 389(2023), 25 vom: 21. Dez., Seite 2341-2354 |w (DE-627)NLM000008184 |x 1533-4406 |7 nnns |
| 773 | 1 | 8 | |g volume:389 |g year:2023 |g number:25 |g day:21 |g month:12 |g pages:2341-2354 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1056/NEJMoa2309995 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 389 |j 2023 |e 25 |b 21 |c 12 |h 2341-2354 | ||