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Infectious Diseases

Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19A Randomized Clinical Trial

Educational Objective
To identify the key insights or developments described in this article

1 Credit CME

JAMA

Published Online: March 4, 2021

Original Investigation

Article Information and Disclosures

Author Affiliations

¹Centro de Estudios en Infectología Pediátrica, Cali, Colombia
²Department of Pediatrics, Universidad del Valle, Cali, Colombia
³Clínica Imbanaco, Cali, Colombia
⁴State Health Department, Valle del Cauca, Colombia
⁵Department of Public Health, Universidad Icesi, Cali, Colombia
⁶POHEMA (Pediatric Oncologist and Hematologist) Foundation, Cali, Colombia
⁷Cali’s Cancer Population-based Registry, Cali, Colombia
⁸Department of Internal Medicine, Universidad del Valle, Cali, Colombia
⁹Christus Sinergia Salud, Cali, Colombia
¹⁰Neurólogos de Occidente, Cali, Colombia
¹¹Clínica de Occidente, Cali, Colombia
¹²Municipal Health Department, Cali, Colombia
¹³Caucaseco Scientific Research Center, Malaria Vaccine and Drug Development Center, Cali, Colombia
¹⁴Department of Microbiology, Universidad del Valle, Cali, Colombia
¹⁵Hemato Oncólogos, Cali, Colombia
¹⁶Health Experts Committee, Valle del Cauca, Colombia
¹⁷Centro Médico Santuario, Cali, Colombia

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US Insurer Spending on Ivermectin Prescriptions for COVID-19

Kao-Ping Chua, MD, PhD; Rena M. Conti, PhD; Nora V. Becker, MD, PhD
Original Investigation

Effect of Ivermectin vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19

Susanna Naggie, MD, MHS; David R. Boulware, MD, MPH; Christopher J. Lindsell, PhD; Thomas G. Stewart, PhD; Nina Gentile, MD; Sean Collins, MD, MSci; Matthew William McCarthy, MD; Dushyantha Jayaweera, MD; Mario Castro, MD, MPH; Mark Sulkowski, MD; Kathleen McTigue, MD, MPH, MS; Florence Thicklin; G. Michael Felker, MD, MHS; Adit A. Ginde, MD, MPH; Carolyn T. Bramante, MD, MPH; Alex J. Slandzicki, MD; Ahab Gabriel, MD; Nirav S. Shah, MD, MPH; Leslie A. Lenert, MD, MS; Sarah E. Dunsmore, PhD; Stacey J. Adam, PhD; Allison DeLong, BS; George Hanna, MD; April Remaly, BA; Rhonda Wilder, MS; Sybil Wilson, RN; Elizabeth Shenkman, PhD; Adrian F. Hernandez, MD, MHS; Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-6) Study Group and Investigators; William (Kelly) Vincent; Raina Vincent; Ray Bianchi; Jen Premas; Diana Cordero-Loperena; Evelyn Rivera; Madhu Gupta ; Greg Karawan; Carey Ziomek; Joseph Arena; Sonaly DeAlmeida; Soroush Ramin; Jaya Nataraj; Michael Paasche-Orlow; Lori Henault; Katie Waite; David Miller; Ginger Brounce; Constance George-Adebayo; Adeolu Adebayo; Jessica Wallan; Alex Slandzicki; Claudia Vogel; Sebastian Munoz; David Kavtaradze; Cassandra Watson; David Singleton; Maria Rivon; Amanda Sevier; Arnold Del Pilar; Amber Spangler; Sohail Rao; Luis Cantu; Arvind Krishna; Kathy Evans; Tylene Falkner; Brandi Kerr; Robert Spees; Mailyn Marta; G. Michael Felker; Amanda Harrington; Rowena Dolor; Madison Frazier; Lorraine Vergara; Jessica Wilson; Valencia Burruss; Terri Hurst; Igho Ofotokun; Laurel Bristow; Rajesh Prabhu; Krystal Klicka; Amber Lightfeather; Vicki James; Marcella Rogers; Pradeep Parihar; De'Ambra Torress; Chukwuemeka Oragwu; Ngozi Oguego; Rajesh Pillai; Mustafa Juma; Ahab Gabriel; Emad Ghaly; Dafer Al-Haddadin; Courtney Ramirez; Gammal Hassanien; Samah Ismail; Andrew Meltzer; Seamus Moran; Scott Brehaut; Angelina Roche; Manisha Mehta; Nicole Koppinger; Jose Baez; Ivone Pagan; Dallal Abdelsayed; Mina Aziz; Philip Robinson; Julie Nguyen; Victoria Pardue; Llisa Hammons; Juan Ruiz-Unger; Susan Gonzalez; Lionel Reyes; John Cienki; Gisselle Jimenez; Jonathan Cohen; Matthew Wong; Ying Yuan; Jeremy Szeto; Mark Sulkowski; Lauren Stelmash; Arch Amon; Daniel Haight; Deryl Lamb; Amron Harper; Nancy Pyram-Bernard; Arlen Quintero; Eftim Adhami; Josette Maria; Diksha Paudel; Oksana Raymond; Jeffrey Summers; Tammy Turner; Leslie Lenert; Sam Gallegos; Elizabeth Ann Szwast; Ahsan Abdulghani; Pravin Vasoya; Conrad Miller; Hawa Wiley; Nirav Shah; Tovah Klein; Julie Castex; Phillip Feliciano; Jacqueline Olivo; Marian Ghaly; Zainub Javed; Alexandra Nawrocki; Anthony Vecchiarelli; Nikki Vigil; Vijaya Cherukuri; Erica Burden; Dawn Linn; Laura Fisher; Vijay Patel; Praksha Patel; Yuti Patel; Leonard Ellison; Jeffrey Harrison; Binod Shah; Sugata Shah; Upinder Singh; Julia Donahue; Yasmin Jazayeri; Anita Gupta ; N Chandrasekar; Beth Moritz; Tabitha Fortt; Anisa Fortt; Ingrid Jones-Ince; Alix McKee; Christy Schattinger; Jason Wilson; Brenda Farlow; Nina Gentile; Lillian Finlaw; Randall Richwine; Tearani Williams; Penny Paizer; Lisa Carson; Edward Michelson; Danielle Austin; Sangeeta Khetpal; Tiffany Cantrell; Drew Franklin; Karissa Marshall; Arvind Mahadevan; Madelyn Rosequist; Martin Gnoni; Crystal Daffner; Carla VandeWeerd; Mitchell Roberts; Mark D'Andrea; Stephen Lim; Wayne Swink; Margaret Powers-Fletcher; Sylvere Mukunzi; Elizabeth Shenkman; Jamie Hensley; Brittney Manning; Carmen Isache; Jennifer Bowman; Angelique Callaghan-Brown; Taylor Scott; Tiffany Schwasinger-Schmidt; Ashlie Cornejo; Dushyantha Jayaweera; Maria Almanzar; Letty Ginsburg; Americo Hajaz; Carolyn Bramante; Matthew Robinson; Michelle Seithel; Akira Sekikawa; Emily Klawson; Luis Ostrosky; Virginia Umana; Thomas Patterson; Robin Tragus; Patrick Jackson; Caroline Hallowell; Heather Haughey; Bhavna Vaidya-Tank; Cameron Gould; Parul Goyal; Carly Gatewood; John Williamson; Hannah Seagle; Matthew McCarthy; Elizabeth Salsgiver; Eddie Armas; Jhonsai Cheng; Priscilla Huerta; Julia Garcia-Diaz; David Aamodt; JaMario Ayers; Jess Collins; John Graves; James Grindstaff; Frank Harrell; Jessica Lai; Itzel Lopez; Jessica Marlin; Alyssa Merkel; Sam Nwosu; Savannah Obregon; Dirk Orozco; Yoli Perez-Torres; Nelson Prato; Colleen Ratcliff; Max Rhode; Russell Rothman; Jana Shirey-Rice; Krista Vermillion; Hsi-Nien Tan; Seibert Tregoning; Meghan Vance; Amber Vongsamphanh; Maria Weir; Nicole Zaleski
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Dispensing of Products for Treatment or Prevention of COVID-19 by US Pharmacies During the Pandemic

Andrew I. Geller, MD; Maribeth C. Lovegrove, MPH; Jennifer N. Lind, PharmD, MPH; S. Deblina Datta, MD; Daniel S. Budnitz, MD, MPH

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Key Points

Question What is the effect of ivermectin on duration of symptoms in adults with mild COVID-19?

Findings In this randomized clinical trial that included 476 patients, the duration of symptoms was not significantly different for patients who received a 5-day course of ivermectin compared with placebo (median time to resolution of symptoms, 10 vs 12 days; hazard ratio for resolution of symptoms, 1.07).

Meaning The findings do not support the use of ivermectin for treatment of mild COVID-19, although larger trials may be needed to understand effects on other clinically relevant outcomes.

Abstract

Importance Ivermectin is widely prescribed as a potential treatment for COVID-19 despite uncertainty about its clinical benefit.

Objective To determine whether ivermectin is an efficacious treatment for mild COVID-19.

Design, Setting, and Participants Double-blind, randomized trial conducted at a single site in Cali, Colombia. Potential study participants were identified by simple random sampling from the state’s health department electronic database of patients with symptomatic, laboratory-confirmed COVID-19 during the study period. A total of 476 adult patients with mild disease and symptoms for 7 days or fewer (at home or hospitalized) were enrolled between July 15 and November 30, 2020, and followed up through December 21, 2020.

Intervention Patients were randomized to receive ivermectin, 300 μg/kg of body weight per day for 5 days (n = 200) or placebo (n = 200).

Main Outcomes and Measures Primary outcome was time to resolution of symptoms within a 21-day follow-up period. Solicited adverse events and serious adverse events were also collected.

Results Among 400 patients who were randomized in the primary analysis population (median age, 37 years [interquartile range {IQR}, 29-48]; 231 women [58%]), 398 (99.5%) completed the trial. The median time to resolution of symptoms was 10 days (IQR, 9-13) in the ivermectin group compared with 12 days (IQR, 9-13) in the placebo group (hazard ratio for resolution of symptoms, 1.07 [95% CI, 0.87 to 1.32]; P = .53 by log-rank test). By day 21, 82% in the ivermectin group and 79% in the placebo group had resolved symptoms. The most common solicited adverse event was headache, reported by 104 patients (52%) given ivermectin and 111 (56%) who received placebo. The most common serious adverse event was multiorgan failure, occurring in 4 patients (2 in each group).

Conclusion and Relevance Among adults with mild COVID-19, a 5-day course of ivermectin, compared with placebo, did not significantly improve the time to resolution of symptoms. The findings do not support the use of ivermectin for treatment of mild COVID-19, although larger trials may be needed to understand the effects of ivermectin on other clinically relevant outcomes.

Trial Registration ClinicalTrials.gov Identifier: NCT04405843

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Article Information

Corresponding Author: Eduardo López-Medina, MD, MSc, Centro de Estudios en Infectología Pediátrica, Calle 5 B 5 No. 37 BIS-28, Cali, Colombia (eduardo.lopez@ceiponline.org).

Accepted for Publication: February 18, 2021.

Published Online: March 4, 2021. doi:10.1001/jama.2021.3071

Author Contributions: Drs López-Medina and Ramirez had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: López-Medina, López, Hurtado, Dávalos, Ramirez, Martínez, Díazgranados, Oñate, Chavarriaga.

Acquisition, analysis, or interpretation of data: López-Medina, Hurtado, Ramirez, Martínez, Oñate, Chavarriaga, Herrera, Parra, Libreros, Jaramillo, Avendaño, Toro, Torres, Lesmes, Rios, Caicedo.

Drafting of the manuscript: López-Medina, Hurtado, Dávalos, Chavarriaga, Caicedo.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: López-Medina, Ramirez.

Obtained funding: López-Medina, López.

Administrative, technical, or material support: Hurtado, Dávalos, Martínez, Díazgranados, Chavarriaga, Herrera, Parra, Libreros, Jaramillo, Avendaño, Toro, Torres, Lesmes, Rios, Caicedo.

Supervision: López-Medina, López, Oñate, Rios, Caicedo.

Conflict of Interest Disclosures: Dr López-Medina reported receiving grants from Sanofi Pasteur, GlaxoSmithKline, and Janssen and personal fees from Sanofi Pasteur during the conduct of the study. Dr López reported receiving grants from Sanofi Pasteur, GlaxoSmithKline, and Janssen and personal fees from Sanofi Pasteur during the conduct of the study. Dr Oñate reported receiving grants from Janssen and personal fees from Merck Sharp & Dohme and Gilead outside the submitted work. Dr Torres reported receiving nonfinancial support from Tecnoquímicas unrelated to this project during the conduct of the study. No other disclosures were reported.

Funding/Support: This study received an unrestricted grant from Centro de Estudios en Infectología Pediátrica (grant ScDi823).

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: In addition to the authors, the following collaborators from Centro de Estudios en Infectología Pediátrica participated in the Estudio Para Evaluar la Ivermectina en COVID-19 (EPIC) trial:

Catalina De La Cruz, MD; Camilo Andrade; Iñigo Prieto, MD, MSc; Viviana Márquez, MD; Mary Luz Hernandez; Carlos Gonzalez, MD; Victoria Aguirre, RN; Gloria Tamayo; Leidy Gomez; Aracelly Romero; Socorro Mutis; Nidia Guaza; Eliana Valencia; James Riascos; Ovidio Maldonado; Laura Victoria, RN; Hilda Giraldo; Lina Solano, RN; Maria F. Collazos, RN; Elizabeth Toro, MD; Carlos Cortés, MD; Alexandra Sierra, MD; Carolina Ospina, MD; Diana P. Mazo, PharmD; Jhon J. Calderón; Jenny Yela, RN; Diego Rivera, RN; and Diana Suárez, PharmD.

Additional Contributions: We are grateful to the patients who participated in this trial; Erika Cantor, MSc, from the Institute of Statistics, Universidad de Valparaíso, Valparaíso, Chile, for her contribution during data analysis; Keith Veitch for his writing assistance; and Neal Alexander, PhD, from CIDEIM in Cali, Colombia, and Rodrigo DeAntonio, DrPH, from Cevaxin in Panamá City, Panamá, for their contribution during study planning. Ms Cantor and Mr Veitch received compensation for their roles in the study. Drs Alexander and DeAntonio did not receive compensation for their roles in the study. We thank Tecnoquímicas for its donation of the investigational product and placebo from August 26, 2020, until the end of the trial.

AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
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