Randomized Trial of Metformin, Ivermectin, and Fluvoxamine for Covid-19.
Adult
Aged
Aged, 80 and over
COVID-19
/ complications
COVID-19 Vaccines
Double-Blind Method
Female
Fluvoxamine
/ therapeutic use
Humans
Hypoxia
/ etiology
Ivermectin
/ therapeutic use
Male
Metformin
/ therapeutic use
Middle Aged
Obesity
/ complications
Overweight
/ complications
Pregnancy
Pregnancy Complications, Infectious
/ drug therapy
SARS-CoV-2
COVID-19 Drug Treatment
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
18 08 2022
18 08 2022
Historique:
entrez:
7
9
2022
pubmed:
8
9
2022
medline:
11
9
2022
Statut:
ppublish
Résumé
Early treatment to prevent severe coronavirus disease 2019 (Covid-19) is an important component of the comprehensive response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. In this phase 3, double-blind, randomized, placebo-controlled trial, we used a 2-by-3 factorial design to test the effectiveness of three repurposed drugs - metformin, ivermectin, and fluvoxamine - in preventing serious SARS-CoV-2 infection in nonhospitalized adults who had been enrolled within 3 days after a confirmed diagnosis of infection and less than 7 days after the onset of symptoms. The patients were between the ages of 30 and 85 years, and all had either overweight or obesity. The primary composite end point was hypoxemia (≤93% oxygen saturation on home oximetry), emergency department visit, hospitalization, or death. All analyses used controls who had undergone concurrent randomization and were adjusted for SARS-CoV-2 vaccination and receipt of other trial medications. A total of 1431 patients underwent randomization; of these patients, 1323 were included in the primary analysis. The median age of the patients was 46 years; 56% were female (6% of whom were pregnant), and 52% had been vaccinated. The adjusted odds ratio for a primary event was 0.84 (95% confidence interval [CI], 0.66 to 1.09; P = 0.19) with metformin, 1.05 (95% CI, 0.76 to 1.45; P = 0.78) with ivermectin, and 0.94 (95% CI, 0.66 to 1.36; P = 0.75) with fluvoxamine. In prespecified secondary analyses, the adjusted odds ratio for emergency department visit, hospitalization, or death was 0.58 (95% CI, 0.35 to 0.94) with metformin, 1.39 (95% CI, 0.72 to 2.69) with ivermectin, and 1.17 (95% CI, 0.57 to 2.40) with fluvoxamine. The adjusted odds ratio for hospitalization or death was 0.47 (95% CI, 0.20 to 1.11) with metformin, 0.73 (95% CI, 0.19 to 2.77) with ivermectin, and 1.11 (95% CI, 0.33 to 3.76) with fluvoxamine. None of the three medications that were evaluated prevented the occurrence of hypoxemia, an emergency department visit, hospitalization, or death associated with Covid-19. (Funded by the Parsemus Foundation and others; COVID-OUT ClinicalTrials.gov number, NCT04510194.).
Sections du résumé
BACKGROUND
Early treatment to prevent severe coronavirus disease 2019 (Covid-19) is an important component of the comprehensive response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic.
METHODS
In this phase 3, double-blind, randomized, placebo-controlled trial, we used a 2-by-3 factorial design to test the effectiveness of three repurposed drugs - metformin, ivermectin, and fluvoxamine - in preventing serious SARS-CoV-2 infection in nonhospitalized adults who had been enrolled within 3 days after a confirmed diagnosis of infection and less than 7 days after the onset of symptoms. The patients were between the ages of 30 and 85 years, and all had either overweight or obesity. The primary composite end point was hypoxemia (≤93% oxygen saturation on home oximetry), emergency department visit, hospitalization, or death. All analyses used controls who had undergone concurrent randomization and were adjusted for SARS-CoV-2 vaccination and receipt of other trial medications.
RESULTS
A total of 1431 patients underwent randomization; of these patients, 1323 were included in the primary analysis. The median age of the patients was 46 years; 56% were female (6% of whom were pregnant), and 52% had been vaccinated. The adjusted odds ratio for a primary event was 0.84 (95% confidence interval [CI], 0.66 to 1.09; P = 0.19) with metformin, 1.05 (95% CI, 0.76 to 1.45; P = 0.78) with ivermectin, and 0.94 (95% CI, 0.66 to 1.36; P = 0.75) with fluvoxamine. In prespecified secondary analyses, the adjusted odds ratio for emergency department visit, hospitalization, or death was 0.58 (95% CI, 0.35 to 0.94) with metformin, 1.39 (95% CI, 0.72 to 2.69) with ivermectin, and 1.17 (95% CI, 0.57 to 2.40) with fluvoxamine. The adjusted odds ratio for hospitalization or death was 0.47 (95% CI, 0.20 to 1.11) with metformin, 0.73 (95% CI, 0.19 to 2.77) with ivermectin, and 1.11 (95% CI, 0.33 to 3.76) with fluvoxamine.
CONCLUSIONS
None of the three medications that were evaluated prevented the occurrence of hypoxemia, an emergency department visit, hospitalization, or death associated with Covid-19. (Funded by the Parsemus Foundation and others; COVID-OUT ClinicalTrials.gov number, NCT04510194.).
Identifiants
pubmed: 36070710
doi: 10.1056/NEJMoa2201662
pmc: PMC9945922
mid: NIHMS1853247
doi:
Substances chimiques
COVID-19 Vaccines
0
Ivermectin
70288-86-7
Metformin
9100L32L2N
Fluvoxamine
O4L1XPO44W
Banques de données
ClinicalTrials.gov
['NCT04510194']
Types de publication
Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
599-610Subventions
Organisme : NIDDK NIH HHS
ID : K23 DK124654
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK048520
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1TR002494
Pays : United States
Organisme : NIDDK NIH HHS
ID : F32 DK123878
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007741
Pays : United States
Organisme : NIDDK NIH HHS
ID : DK124654-01A1
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR002492
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2TR002492
Pays : United States
Investigateurs
Blake Anderson
(B)
Riannon C Atwater
(RC)
Nandini Avula
(N)
Kenny B Beckman
(KB)
Hrishikesh K Belani
(HK)
David R Boulware
(DR)
Carolyn T Bramante
(CT)
Jannis Brea
(J)
Courtney A Broedlow
(CA)
John B Buse
(JB)
Paula Campora
(P)
Jill Charles
(J)
Grace Christensen
(G)
Theresa Christiansen
(T)
Ken Cohen
(K)
Bo Connelly
(B)
Srijani Datta
(S)
Nikita Deng
(N)
Alex T Dunn
(AT)
Spencer M Erickson
(SM)
Faith M Fairbairn
(FM)
Sarah L Fenno
(SL)
Daniel J Fraser
(DJ)
Regina D Fricton
(RD)
Gwen Griffiths
(G)
Aubrey A Hagen
(AA)
Katrina M Hartman
(KM)
Audrey F Hendrickson
(AF)
Jared D Huling
(JD)
Nicholas E Ingraham
(NE)
Arthur C Jeng
(AC)
Darrell M Johnson
(DM)
Amy B Karger
(AB)
Nichole R Klatt
(NR)
Erik A Kuehl
(EA)
Derek D LaBar
(DD)
Samuel Lee
(S)
David M Liebovitz
(DM)
Sarah Lindberg
(S)
Darlette G Luke
(DG)
Rosario Machicado
(R)
Zeinab Mohamud
(Z)
Thomas A Murray
(TA)
Rumbidzai Ngonyama
(R)
Jacinda M Nicklas
(JM)
David J Odde
(DJ)
Elliott Parrens
(E)
Daniela Parra
(D)
Barkha Patel
(B)
Jennifer L Proper
(JL)
Matthew F Pullen
(MF)
Michael A Puskarich
(MA)
Via Rao
(V)
Neha V Reddy
(NV)
Naveen Reddy
(N)
Katelyn J Rypka
(KJ)
Hanna G Saveraid
(HG)
Paula Seloadji
(P)
Arman Shahriar
(A)
Nancy Sherwood
(N)
Jamie L Siegart
(JL)
Lianne K Siegel
(LK)
Lucas Simmons
(L)
Isabella Sinelli
(I)
Palak Singh
(P)
Andrew Snyder
(A)
Maxwell T Stauffer
(MT)
Jennifer Thompson
(J)
Christopher J Tignanelli
(CJ)
Tannon L Tople
(TL)
Walker J Tordsen
(WJ)
Ray H B Watson
(RHB)
Beiqing Wu
(B)
Adnin Zaman
(A)
Madeline R Zolik
(MR)
Lena Zinkl
(L)
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2022 Massachusetts Medical Society.
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