Ivermectin Accelerates Circulating Nonstructural Protein 1 (NS1) Clearance in Adult Dengue Patients: A Combined Phase 2/3 Randomized Double-blinded Placebo Controlled Trial

• Main Authors: Yupin Suputtamongkol, Panisadee Avirutnan, Dumrong Mairiang, Nasikarn Angkasekwinai, Kannika Niwattayakul, Eakkawit Yamasmith, Fadhil A.Hamad Saleh-Arong, Adisak Songjaeng, Tanapan Prommool, Nattaya Tangthawornchaikul, Chunya Puttikhunt, Saowalak Hunnangkul, Chulaluk Komoltri, Suwich Thammapalo, Prida Malasit
• Other Authors: Siriraj Hospital
• Format: Article
• Published: 2022
• Subjects: Medicine
• Online Access: https://repository.li.mahidol.ac.th/handle/123456789/78200
• Institution: Mahidol University

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.