Ivermectin Accelerates Circulating Nonstructural Protein 1 (NS1) Clearance in Adult Dengue Patients: A Combined Phase 2/3 Randomized Double-blinded Placebo Controlled Trial
- 19 January 2021
- journal article
- research article
- Published by Oxford University Press (OUP) in Clinical Infectious Diseases
- Vol. 72 (10), e586-e593
- https://doi.org/10.1093/cid/ciaa1332
Abstract
Background Dengue is the most significant mosquito-borne viral disease; there are no specific therapeutics. The antiparasitic drug ivermectin efficiently inhibits the replication of all 4 dengue virus serotypes in vitro. Methods We conducted 2 consecutive randomized, double-blind, placebo-controlled trials in adult dengue patients to evaluate safety and virological and clinical efficacies of ivermectin. After a phase 2 trial with 2 or 3 days of 1 daily dose of 400 µg/kg ivermectin, we continued with a phase 3, placebo-controlled trial with 3 days of 400 µg/kg ivermectin. Results The phase 2 trial showed a trend in reduction of plasma nonstructural protein 1 (NS1) clearance time in the 3-day ivermectin group compared with placebo. Combining phase 2 and 3 trials, 203 patients were included in the intention to treat analysis (100 and 103 patients receiving ivermectin and placebo, respectively). Dengue hemorrhagic fever occurred in 24 (24.0%) of ivermectin-treated patients and 32 (31.1%) patients receiving placebo (P = .260). The median (95% confidence interval [CI]) clearance time of NS1 antigenemia was shorter in the ivermectin group (71.5 [95% CI 59.9–84.0] hours vs 95.8 [95% CI 83.9–120.0] hours, P = .014). At discharge, 72.0% and 47.6% of patients in the ivermectin and placebo groups, respectively had undetectable plasma NS1 (P = .001). There were no differences in the viremia clearance time and incidence of adverse events between the 2 groups. Conclusions A 3-day 1 daily dose of 400 µg/kg oral ivermectin was safe and accelerated NS1 antigenemia clearance in dengue patients. However, clinical efficacy of ivermectin was not observed at this dosage regimen.Keywords
Funding Information
- Thailand Research Fund (RDG59D0011)
- Faculty of Medicine Siriraj Hospital (R015936007)
- Ministry of Public Health (R015745005 and R015845009)
- Mahidol University
This publication has 30 references indexed in Scilit:
- Determination of Viremia and Concentration of Circulating Nonstructural Protein 1 in Patients Infected with Dengue Virus in MexicoThe American Journal of Tropical Medicine and Hygiene, 2013
- Dengue Viral RNA Levels in Peripheral Blood Mononuclear Cells Are Associated with Disease Severity and Preexisting Dengue Immune StatusPLOS ONE, 2012
- Effects of Short-Course Oral Corticosteroid Therapy in Early Dengue Infection in Vietnamese Patients: A Randomized, Placebo-Controlled TrialClinical Infectious Diseases, 2012
- A Randomized, Double-Blind Placebo Controlled Trial of Balapiravir, a Polymerase Inhibitor, in Adult Dengue PatientsThe Journal of Infectious Diseases, 2012
- Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virusBiochemical Journal, 2012
- Use of High‐Dose, Twice‐Yearly Albendazole and Ivermectin to SuppressWuchereria bancroftiMicrofilarial LevelsClinical Infectious Diseases, 2010
- A Randomized Controlled Trial of Chloroquine for the Treatment of Dengue in Vietnamese AdultsPLoS Neglected Tropical Diseases, 2010
- High Circulating Levels of the Dengue Virus Nonstructural Protein NS1 Early in Dengue Illness Correlate with the Development of Dengue Hemorrhagic FeverThe Journal of Infectious Diseases, 2002
- Dengue Viremia Titer, Antibody Response Pattern, and Virus Serotype Correlate with Disease SeverityThe Journal of Infectious Diseases, 2000
- Ivermectin in human medicineJournal of Antimicrobial Chemotherapy, 1994