Use of Ivermectin Is Associated With Lower Mortality in Hospitalized Patients With Coronavirus Disease 2019: The Ivermectin in COVID Nineteen Study
Juliana Cepelowicz Rajter, Michael S Sherman, Naaz Fatteh, Fabio Vogel, Jamie Sacks, Jean-Jacques Rajter, Juliana Cepelowicz Rajter, Michael S Sherman, Naaz Fatteh, Fabio Vogel, Jamie Sacks, Jean-Jacques Rajter
Abstract
Background: Ivermectin was shown to inhibit severe acute respiratory syndrome coronavirus 2 replication in vitro, which has led to off-label use, but clinical efficacy has not been described previously.
Research question: Does ivermectin benefit hospitalized coronavirus disease 2019 (COVID-19) patients?
Study design and methods: Charts of consecutive patients hospitalized at four Broward Health hospitals in Florida with confirmed COVID-19 between March 15 and May 11, 2020, treated with or without ivermectin were reviewed. Hospital ivermectin dosing guidelines were provided, but treatment decisions were at the treating physician's discretion. The primary outcome was all-cause in-hospital mortality. Secondary outcomes included mortality in patients with severe pulmonary involvement, extubation rates for mechanically ventilated patients, and length of stay. Severe pulmonary involvement was defined as need for Fio2 ≥ 50%, noninvasive ventilation, or invasive ventilation at study entry. Logistic regression and propensity score matching were used to adjust for confounders.
Results: Two hundred eighty patients, 173 treated with ivermectin and 107 without ivermectin, were reviewed. Most patients in both groups also received hydroxychloroquine, azithromycin, or both. Univariate analysis showed lower mortality in the ivermectin group (15.0% vs 25.2%; OR, 0.52; 95% CI, 0.29-0.96; P = .03). Mortality also was lower among ivermectin-treated patients with severe pulmonary involvement (38.8% vs 80.7%; OR, 0.15; 95% CI, 0.05-0.47; P = .001). No significant differences were found in extubation rates (36.1% vs 15.4%; OR, 3.11; 95% CI, 0.88-11.00; P = .07) or length of stay. After multivariate adjustment for confounders and mortality risks, the mortality difference remained significant (OR, 0.27; 95% CI, 0.09-0.80; P = .03). One hundred ninety-six patients were included in the propensity-matched cohort. Mortality was significantly lower in the ivermectin group (13.3% vs 24.5%; OR, 0.47; 95% CI, 0.22-0.99; P < .05), an 11.2% (95% CI, 0.38%-22.1%) absolute risk reduction, with a number needed to treat of 8.9 (95% CI, 4.5-263).
Interpretation: Ivermectin treatment was associated with lower mortality during treatment of COVID-19, especially in patients with severe pulmonary involvement. Randomized controlled trials are needed to confirm these findings.
Keywords: hospitalized COVID-19; in-hospital mortality; ivermectin; mechanical ventilation; number needed to treat; severe pulmonary involvement; survival.
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
References
- Navarro M., Camprubí D., Requena-Méndez A. Safety of high-dose ivermectin: a systematic review and meta-analysis. J Antimicrobial Chemother. 2020;75:827–834.
- Boldescu V., Behnam M.A.M., Vasilakis N., Klein C.D. Broad-spectrum agents for flaviviral infections: dengue, Zika and beyond. Nat Rev Drug Discov. 2017;16:565–586.
- Wagstaff K.M., Sivakumaran H., Heaton S.M., Harrich D., Jans D.A. Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. Biochem J. 2012;443:851–856.
- Caly L., Druce J.D., Catton M.G., Jans D.A., Wagstaff K.M. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res. 2020;178:104787.
- Munoz J., Ballester M.R., Antonijoan R.M. Safety and pharmacokinetic profile of fixed dose ivermectin with an innovative 18 mg tablet in healthy adult volunteers. PLoS Negl Trop Dis. 2018;12(1)
- Richardson S., Hirsch J.S., Narasimha M. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA. 2020;323(20):2052–2059.
- Zhou F., Yu T., Du R. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054–1062.
- Magagnoli J., Narendran S., Pereira F. Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19. [published online ahead of print April 23, 2020]. medRxiv.
- Horby P, Lim WS, Emberson JR, et al. RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19-preliminary report [published online ahead of print July 7, 2020]. N Engl J Med. .
- Garg S., Kim L., Whitaker M. Hospitalization rates and characteristics of patients hospitalized with laboratory-confirmed coronavirus disease 2019—COVID-NET, 14 states, March 1-30, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(15):458–464.
- Price C.C., Altice F.L., Shyr Y. Tocilizumab treatment for cytokine release syndrome in hospitalized COVID-19 patients: survival and clinical outcomes. Chest. 2020;158(4):1397–1408.
Source: PubMed