Critical Care Explorations (Nov 2021)

Variation in Use of Repurposed Medications Among Patients With Coronavirus Disease 2019. From The Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study: Coronavirus Disease 2019 Registry Investigator Group

  • Michael A. Garcia, MD,
  • Shelsey W. Johnson, MD,
  • Nicholas A. Bosch, MD, MSc,
  • Emily K. Sisson, MA,
  • Christopher R. Sheldrick, PhD,
  • Vishakha K. Kumar, MD, MBA,
  • Karen Boman, BS,
  • Scott Bolesta, PharmD,
  • Vikas Bansal, MBBS, MPH,
  • Neha Deo, BS,
  • J. P. Domecq, MD,
  • Amos Lal, MD,
  • Amy B. Christie, MD,
  • Valerie M. Banner-Goodspeed, MPH,
  • Devang Sanghavi, MD, MHA,
  • Girish Vadgaonkar, MBBS,
  • Ognjen Gajic, MD, MSc,
  • Rahul Kashyap, MBBS, MBA,
  • Allan J. Walkey, MD, MSc,
  • for the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study Investigators,
  • Jean-Baptiste Mesland,
  • Pierre Henin,
  • Hélène Petre,
  • Isabelle Buelens,
  • Anne-Catherine Gerard,
  • Philippe Clevenbergh,
  • Dragana Markotić,
  • Ivana Bošnjak,
  • Ruben Garza,
  • Eric Chu,
  • Victoria Chan,
  • Oscar Y Gavidia,
  • Felipe Pachon,
  • Yeimy A Sanchez,
  • Mohamed El Kassas,
  • Mohamed Badr,
  • Ahmed Tawheed,
  • Ahmed Tawheed,
  • Hend Yahia,
  • Jose Luis Ramos Coello,
  • Guillermo Perez,
  • Ana Karen Vallecillo Lizardo,
  • Gabina María Reyes Guillen,
  • Helin Archaga Soto,
  • Smitha S. Segu,
  • Tuhin Chakraborty,
  • Epcebha Joyce,
  • Girish Vadgaonkar,
  • Rekha Ediga,
  • Shilpa Basety,
  • Shwetha Dammareddy,
  • Phani Sreeharsha Kasumalla,
  • Umamaheswara Raju,
  • Janaki Manduva,
  • Naresh Kolakani,
  • Shreeja Sripathi,
  • Sheetal Chaitanya,
  • Mradul Kumar Daga,
  • Munisha Agarwal,
  • Ishan Rohtagi,
  • Sridhar Papani,
  • Mahesh Kamuram,
  • Kamlesh Kumar Agrawal,
  • Vijendra Baghel,
  • Kirti Kumar Patel,
  • Surapaneni Krishna Mohan,
  • Ekambaram Jyothisree,
  • Wataru Matsuda,
  • Reina Suzuki,
  • Michihito Kyo,
  • Yuki Itagaki,
  • Akira Kodate,
  • Reina Suzuki,
  • Akira Kodate,
  • Yuki Takahashi,
  • Koyo Moriki,
  • Fatimah Hassan-Hanga,
  • Hadiza Galadanci,
  • Abubakar Shehu Gezawa,
  • Halima M. S. Kabara,
  • Taiwo Gboluwaga Amole,
  • Halima Kabir,
  • Dalha Gwarzo Haliru,
  • Abdullahi S Ibrahim,
  • Muhammad Sohaib Asghar,
  • Mashaal Syed,
  • Syed Anosh Ali Naqvi,
  • Igor Borisovich Zabolotskikh,
  • Konstantin Dmitrievich Zybin,
  • Sergey Vasilevich Sinkov,
  • Tatiana Sergeevna Musaeva,
  • Mohammed A Almazyad,
  • Mohammed I Alarifi,
  • Jara M Macarambon,
  • Ahmad Abdullah Bukhari,
  • Hussain A. Albahrani,
  • Kazi N Asfina,
  • Kaltham M Aldossary,
  • Marija Zdravkovic,
  • Zoran Todorovic,
  • Viseslav Popadic,
  • Slobodan Klasnja,
  • Bojan Kovacevic,
  • Jovana Bojicic,
  • Predrag D Stevanovic,
  • Dejan S Stojakov,
  • Duska K Ignjatovic,
  • Suzana C Bojic,
  • Marina M Bobos,
  • Irina B Nenadic,
  • Milica S Zaric,
  • Marko D Djuric,
  • Vladimir R Djukic,
  • Santiago Y. Teruel,
  • Belen C. Martin,
  • Santiago Y. Teruel,
  • Uluhan Sili,
  • Huseyin Bilgin,
  • Pinar Ay,
  • Abhijit A Raval,
  • Andrea Franks,
  • Anmol Kharbanda,
  • Sunil Jhajhria,
  • Zachary Fyffe,
  • Stephen Capizzi,
  • Bethany Alicie,
  • Martha Green,
  • Lori Crockarell,
  • Amelia Drennan,
  • Kathleen Dubuque,
  • Tonya Fambrough,
  • Nikole Gasaway,
  • Briana Krantz,
  • Peiman Nebi,
  • Jan Orga,
  • Margaret Serfass,
  • Alina Simion,
  • Kimberly Warren,
  • Cassie Wheeler,
  • CJ Woolman,
  • Amy B. Christie,
  • Dennis W. Ashley,
  • Rajani Adiga,
  • Andrew S. Moyer,
  • George M. Verghese,
  • Andrea Sikora Newsome,
  • Christy C. Forehand,
  • Rebecca Bruning,
  • Timothy W. Jones,
  • Moldovan Sabov,
  • Fatema Zaidi,
  • Fiona Tissavirasingham,
  • Dhatri Malipeddi,
  • Donna Lee Armaignac,
  • Don Parris,
  • Maria Pilar Zuniga,
  • Ilea Vargas,
  • Viviana Boronat,
  • Anneka Hutton,
  • Navneet Kaur,
  • Prashank Neupane,
  • Nohemi Sadule-Rios,
  • Lourdes M. Rojas,
  • Aashish Neupane,
  • Priscilla Rivera,
  • Carlos Valle Carlos,
  • Gregory Vincent,
  • Valerie M. Banner-Goodspeed,
  • Somnath Bose,
  • Lauren E. Kelly,
  • Melisa Joseph,
  • Marie McGourty,
  • Krystal Capers,
  • Benjamin Hoenig,
  • Maria C. Karamourtopoulos,
  • Anica C. Law,
  • Elias N. Baedorf Kassis,
  • Allan J. Walkey,
  • Sushrut S. Waikar,
  • Michael A. Garcia,
  • Mia Colona,
  • Zoe Kibbelaar,
  • Michael Leong,
  • Daniel Wallman,
  • Kanupriya Soni,
  • Jennifer Maccarone,
  • Joshua Gilman,
  • Ycar Devis,
  • Joseph Chung,
  • Munizay Paracha,
  • David N. Lumelsky,
  • Madeline DiLorenzo,
  • Najla Abdurrahman,
  • Shelsey Johnson,
  • Kimberly Zammit,
  • Patrick, J McGrath,
  • William Loeffler,
  • Maya, R Chilbert,
  • Raghavendra Tirupathi,
  • Alymer Tang,
  • Arshad Safi,
  • Cindy Green,
  • Jackie Newell,
  • Katja M. Gist,
  • Imran A Sayed,
  • John Brinton,
  • Larisa Strom,
  • Steven K. Daugherty,
  • Sam Atkinson,
  • Kelly Shrimpton,
  • David P. Yamane,
  • Ivy Benjenk,
  • Nivedita Prasanna,
  • Norma Smalls,
  • Michael Smith,
  • William Snow,
  • Riley Liptak,
  • Hannah Durant,
  • Valerie Pendleton,
  • Alay Nanavati,
  • Risa Mrozowsk,
  • Yuk Ming Liu,
  • Sarah Zavala,
  • Sarah Zavala,
  • Esther Shim,
  • Ronald A. Reilkoff,
  • Julia A. Heneghan,
  • Sarah Eichen,
  • Lexie Goertzen,
  • Scott Rajala,
  • Ghislaine Feussom,
  • Ben Tang,
  • Christine C. Junia,
  • Robert Lichtenberg,
  • Hasrat Sidhu,
  • Diana Espinoza,
  • Shelden Rodrigues,
  • Maria Jose Zabala,
  • Daniela Goyes,
  • Ammu Susheela,
  • Buddhi Hatharaliyadda,
  • Naveen Rameshkumar,
  • Amulya Kasireddy,
  • Genessis Maldonado,
  • Lisseth Beltran,
  • Akshata Chaugule,
  • Hassan Khan,
  • Rodrigo Cartin-Ceba,
  • Ayan Sen,
  • Amanda Palacios,
  • Giyth M. Mahdi,
  • Rahul Kashyap,
  • Ognjen Gajic,
  • Vikas Bansal,
  • Aysun Tekin,
  • Amos Lal,
  • John C. O’Horo,
  • Neha N. Deo,
  • Mayank Sharma,
  • Shahraz Qamar,
  • Juan Pablo Domecq,
  • Romil Singh,
  • Alex Niven,
  • Abigail La Nou,
  • Marija Bogojevic,
  • Barbara Mullen,
  • Devang Sanghavi,
  • Pablo Moreno Franco,
  • Pramod Guru,
  • Karthik Gnanapandithan,
  • Hollie Saunders,
  • Zachary Fleissner,
  • Juan Garcia,
  • Alejandra Yu,
  • Lee Mateus,
  • Siva Naga Yarrarapu,
  • Nirmaljot Kaur,
  • Abhisekh Giri,
  • Syed Anjum Khan,
  • Juan Pablo Domecq,
  • Nitesh Kumar Jain,
  • Thoyaja Koritala,
  • Jessica Timmer,
  • Kimberly Welker,
  • Chakradhar Venkata,
  • Miriam Engemann,
  • Annamarie Mantese,
  • Anna Eschler,
  • Mary Hejna,
  • Emily Lewandowski,
  • Kristen Kusmierski,
  • Clare Martin,
  • Bhagat S. Aulakh,
  • Sandeep Tripathi,
  • Jennifer A. Bandy,
  • Lisa M. Kreps,
  • Dawn R. Bollinger,
  • Roger Scott Stienecker,
  • Andre G. Melendez,
  • Tressa A. Brunner,
  • Sue M Budzon,
  • Jessica L. Heffernan,
  • Janelle M. Souder,
  • Tracy L. Miller,
  • Andrea G. Maisonneuve,
  • Brian L. Delmonaco,
  • Anthony Franklin,
  • Mitchell Heath,
  • Antonia L. Vilella,
  • Sara B. Kutner,
  • Kacie Clark,
  • Danielle Moore,
  • Harry L. Anderson, III,
  • Dixy Rajkumar,
  • Ali Abunayla,
  • Jerrilyn Heiter,
  • Howard A. Zaren,
  • Stephanie J. Smith,
  • Grant C. Lewis,
  • Lauren Seames,
  • Cheryl Farlow,
  • Judy Miller,
  • Gloria Broadstreet,
  • Anthony Martinez,
  • Micheal Allison,
  • Aniket Mittal,
  • Rafael Ruiz,
  • Aleta Skaanland,
  • Robert Ross,
  • Paul K Mohabir,
  • Connor G O’Brien,
  • Komal Dasani,
  • Neha Gupta,
  • Tracy L Jones,
  • Shonda C Ayers,
  • Amy B Harrell,
  • Brent R Brown,
  • Megan Edwards,
  • Caleb Darby,
  • Kristy Page,
  • Amanda Brown,
  • Jessie McAbee,
  • Katherine A. Belden,
  • Michael Baram,
  • Devin M. Weber,
  • Rosalie DePaola,
  • Yuwei Xia,
  • Hudson Carter,
  • Aaron Tolley,
  • Mary Barletta,
  • Mary Ferranti,
  • Benjamin J Sines,
  • Thomas J Bice,
  • Patrick W. McGonagill,
  • Colette Galet,
  • Janice Hubbard,
  • David Wang,
  • Lauren Allan,
  • Aditya Badheka,
  • Madhuradhar Chegondi,
  • Usman Nazir,
  • Garrett Rampon,
  • Jake Riggle,
  • Nathan Dismang,
  • Roger A. Alvarez,
  • Amarilys Alarcon-Calderon,
  • Marie Anne Sosa,
  • Sunita K. Mahabir,
  • Mausam J. Patel,
  • Dima Dandachi,
  • Hariharan Regunath,
  • Maraya N. Camazine,
  • Grant. E. Geiger,
  • Abdoulie O. Njai,
  • Baraa M. Saad,
  • Renee D. Stapleton,
  • Anne E. Dixon,
  • Olivia Johnson,
  • Sara S. Ardren,
  • Stephanie Burns,
  • Anna Raymond,
  • Erika Gonyaw,
  • Kevin Hodgdon,
  • Chloe Housenger,
  • Benjamin Lin,
  • Karen McQuesten,
  • Heidi Pecott-Grimm,
  • Julie Sweet,
  • Sebastian Ventrone,
  • Ashish K. Khanna,
  • Lynne Harris,
  • Bruce Cusson,
  • Jacob Fowler,
  • David Vaneenenaam,
  • Glen McKinney,
  • Imoh Udoh,
  • Kathleen Johnson,
  • Vishwanath Pattan,
  • Jessica Papke,
  • Ismail Jimada,
  • Nida Mhid,
  • Samuel Chakola,
  • Kevin Sheth,
  • Abdalla Ammar,
  • Mahmoud Ammar,
  • Victor Torres Lopez,
  • Charles Dela Cruz,
  • Akhil Khosla,
  • Samir Gautam

DOI
https://doi.org/10.1097/CCE.0000000000000566
Journal volume & issue
Vol. 3, no. 11
p. e0566

Abstract

Read online

IMPORTANCE:. At the start of the coronavirus disease 2019 pandemic, medications repurposed for management of coronavirus disease 2019 were used in the absence of clinical trial evidence. OBJECTIVES:. To describe the variation and evolution in use of repurposed medications for coronavirus disease 2019. DESIGN, SETTING, AND PARTICIPANTS:. Observational cohort study of adults hospitalized with coronavirus disease 2019 between February 15, 2020, and April 12, 2021, across 76 United States and international hospitals within the Society of Critical Care Medicine’s Discovery Viral Infection and Respiratory Illness Universal Study coronavirus disease 2019 registry. MAIN OUTCOMES AND MEASURES:. Hospital variation was quantified using multivariable adjusted random effects logistic regression models and unsupervised clustering. Repurposed medications included antivirals, corticosteroids, hydroxychloroquine, immunomodulators, and therapeutic dose anticoagulants. RESULTS:. Among 7,069 adults hospitalized with coronavirus disease 2019, 1,979 (28%) received antivirals, 2,876 (41%) received corticosteroids, 1,779 (25%) received hydroxychloroquine, 620 (9%) received immunomodulators, and 2,154 (31%) received therapeutic dose anticoagulants. Contribution of hospital site to risk-adjusted variation was 46% for antivirals, 30% for corticosteroids, 48% for hydroxychloroquine, 46% for immunomodulators, and 52% for therapeutic dose anticoagulants. Compared with the early pandemic, the later pandemic practice phenotypes converged with increased use of antivirals (odds ratio, 3.14; 95% CI, 2.40–4.10) and corticosteroids (odds ratio, 5.43; 95% CI, 4.23–6.97), with decreased use of hydroxychloroquine (odds ratio, 0.02; 95% CI, 0.01–0.04) and immunomodulators (odds ratio, 0.49; 95% CI, 0.34–0.70). There was no clinically significant change in the use of therapeutic dose anticoagulants (odds ratio, 1.01; 95% CI, 1.01–1.02). There were no differences in risk-adjusted mortality between hospitals with high rates of repurposed medication use compared with hospitals with low rates of use. CONCLUSIONS AND RELEVANCE:. Hospital variation in the use of repurposed medications varied widely across hospitals early in the pandemic and later converged with the emergence of randomized clinical trials. Platforms developed for rapid activation and enrollment in clinical trials of repurposed medications are needed prior to the next pandemic to expedite effective, evidence-based practice.