An open label, block randomized, community study of the safety and efficacy of co-administered ivermectin, diethylcarbamazine plus albendazole vs. diethylcarbamazine plus albendazole for lymphatic filariasis in India

PLoS Negl Trop Dis. 2021 Feb 16;15(2):e0009069. doi: 10.1371/journal.pntd.0009069. eCollection 2021 Feb.

Abstract

Background: Better drug regimens for mass drug administration (MDA) could accelerate the Global Programme to Eliminate Lymphatic Filariasis (LF). This community study was designed to compare the safety and efficacy of MDA with IDA (ivermectin, diethylcarbamazine and albendazole) or DA (diethylcarbamazine and albendazole) in India.

Methodology/principal findings: This two-armed, open-labelled, block randomised, community study was conducted in LF endemic villages in Yadgir district, Karnataka, India. Consenting participants ≥5 years of age were tested for circulating filarial antigenemia (CFA) and microfilaremia (Mf) before treatment with a single oral dose of IDA or DA. Adverse events (AEs) were monitored actively for two days and passively for five more days. Persons with positive CFA or Mf tests at baseline were retested 12-months post-treatment to assess treatment efficacy. Baseline CFA and Mf-rates were 26.4% and 6.9% in IDA and 24.5% and 6.4% in DA villages respectively. 4758 and 4160 participants received IDA and DA. Most AEs were mild after both treatments; fewer than 0.1% of participants experienced AEs with severity > grade 1. No serious AEs were observed. Fever, headache and dizziness were the most common AEs. AE rates were slightly higher after IDA than DA (8.3% vs. 6.4%, P<0.01). AEs were more frequent in females and Mf-positives after either treatment, but significantly more frequent after IDA (40.5% vs 20.2%, P < 0.001). IDA was more effective for clearing Mf than DA (84% vs. 61.8%, P < 0.001). Geometric mean Mf counts per 60μl in retested Mf-positives decreased by 96.4% from 11.8 after IDA and by 90.0% from 9.5 after DA. Neither treatment was effective for clearing CFA.

Conclusions/significance: IDA had an acceptable safety profile and was more effective for clearing Mf than DA. With adequate compliance and medical support to manage AEs, IDA has the potential to accelerate LF elimination in India.

Trial registration: Clinical Trial Registry of India (CTRI No/2016/10/007399).

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Albendazole / administration & dosage*
  • Albendazole / adverse effects
  • Animals
  • Child
  • Diethylcarbamazine / administration & dosage*
  • Diethylcarbamazine / adverse effects
  • Drug-Related Side Effects and Adverse Reactions
  • Elephantiasis, Filarial / drug therapy*
  • Female
  • Filaricides / administration & dosage*
  • Filaricides / adverse effects
  • Humans
  • India
  • Ivermectin / administration & dosage*
  • Ivermectin / adverse effects
  • Male
  • Mass Drug Administration
  • Wuchereria bancrofti / immunology
  • Wuchereria bancrofti / isolation & purification

Substances

  • Filaricides
  • Ivermectin
  • Albendazole
  • Diethylcarbamazine

Associated data

  • CTRI/CTRI2016/10/007399

Grants and funding

This study was supported in part by grant OPPGH5342 from the Bill & Melinda Gates Foundation to Washington University. The study was also supported in part by the Coalition for Operational Research on Neglected Tropical Diseases Support Centre, which is funded at the Task Force for Global Health primarily by the Bill & Melinda Gates Foundation, by the United Kingdom Department for International Development, and by the United States Agency for International Development through its Neglected Tropical Diseases Program. Ivermectin was donated by Merck Sharp Dohme (MSD), also known as Merck & Co. (Kenilworth, NJ, USA). Albendazole (produced and donated by GlaxoSmithKline) and diethylcarbamazine (DEC, produced and donated by Eisai Co.) were obtained from the stocks of Ministry of Health and Family Welfare, Govt of India. The funders and drug donors had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.