Cluster RCT of Co-administration Azithromycin, Albendazole & Ivermectin

Safety of the Co-administration of Azithromycin, Albendazole and Ivermectin Versus Standard Treatment Regimens During Mass Drug Administration (MDA) in Ethiopia: a Cluster-randomized Trial

Cluster-randomised trial comparing co-administration of Azithromycin/Ivermectin/Albendazole with separate administration of Azithromycin and Ivermectin/Albendazole.

The study will be conducted in Beneshangul-Gumuz region, Ethiopia. Within this district, a study group of 8,000 people (in approximately 40 clusters) will receive the azithromycin, ivermectin & albendazole at a single time. A control group of 8,000 people (in approximately 40 clusters) within the same district will receive the current MDA treatment schedule beginning with Ivermectin/Albendazole followed two weeks later with azithromycin. All drug dosing will be in line with standard FMOH and WHO Guidelines for MDA for trachoma and lymphatic filariasis.

The study will randomly sort subdistrict communities (Gotes) into the trial arm and the control arm. The study will compare the number of adverse events (AEs) and severe adverse events (SAEs) between the two arms to determine if co-administration is not inferior to the standard treatment. The primary outcome will be to demonstrate the safety of the triple-drug administration as measured by incidence of AEs/SAEs following the MDA.

Study Overview

• Status: Completed
• Conditions: Lymphatic Filariases; Trachoma
• Intervention / Treatment: Drug: Administration of Albendazole on Day 1; Drug: Administration of Ivermectin on Day 1; Drug: Administration of Azithromycin on Day 15; Drug: Administration of Azithromycin on Day 1

• Study Type: Interventional
• Enrollment (Actual): 13511
• Phase: Phase 4

Contacts and Locations

Study Locations

• Ethiopia
  • Community Recruitment Across Whole District, Ethiopia
    • Community Recruitment across whole district

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Residing in the community for at least three months;
2. Eligible to receive all three agents according to standard MDA criteria

Exclusion Criteria:

1. Not eligible to receive one or more drugs according to standard MDA criteria;
2. Less than 5 years of age (not eligible for ivermectin)**
3. Pregnant women (azithromycin only, not eligible for albendazole and ivermectin)
4. Lactating women (Only administered azithromycin and albendazole, not eligible for ivermectin)**
5. History of allergies to the drugs being studied (azithromycin, ivermectin, albendazole)

6. Residents who cannot swallow tablets

   • Note that patients that are not eligible for IVM, will receive azithromycin and albendazole. Patients that receive azithromycin and albendazole will be followed up through the same procedure as the triple drug therapy to try to track any AEs attributed to the two drug combination.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Separate Administration; Standard administration of Albendazole/Ivermectin separated from administration of azithromycin	Drug: Administration of Albendazole on Day 1; Participants will receive Albendazole 400mg on study day 1.; Drug: Administration of Ivermectin on Day 1; Participants will receive Ivermectin 150mcg/kg (max 12mg) on study day 1. Doses of Ivermectin will be determined using a standard dosing pole.; Drug: Administration of Azithromycin on Day 15; Participants will receive Azithromycin 20mg/kg (max 1gm) on study day 15. Doses of Azithromycin will be determined using a standard dosing pole.
Experimental: Co-administration; Combined administration of Albendazole/Ivermectin/Azithromycin at a single time point	Drug: Administration of Albendazole on Day 1; Participants will receive Albendazole 400mg on study day 1.; Drug: Administration of Ivermectin on Day 1; Participants will receive Ivermectin 150mcg/kg (max 12mg) on study day 1. Doses of Ivermectin will be determined using a standard dosing pole.; Drug: Administration of Azithromycin on Day 1; Participants will receive Azithromycin 20mg/kg (max 1gm) on study day 1. Doses of Azithromycin will be determined using a standard dosing pole.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Self Reported Adverse Event	The incidence of self-reported adverse events following MDA. We will collect data on the presence of common symptoms/signs prior to drug administration. All patients will be reviewed 24-48 hours after treatment and asked to report adverse events. We will calculate the proportion of newly occurring adverse events following treatment and calculate the whether the proportion of patients experiencing an adverse event differs between study arms,	1 Month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cost of Administration Drug Separately compared to Cost of Co-Administration of Drugs	Analysis of the cost effectiveness of co-administration compared to separate administration of drugs	1 month
Community perceptions	An analysis of community perceptions of benefits of co-administration at a single time point vs standard separated MDA will be conducted by conducting focus groups and in-depth interviews with study participants.	1 month

Collaborators and Investigators

• Sponsor: London School of Hygiene and Tropical Medicine
• Collaborators: Federal Minstry of Health of Ethiopia; Armauer Hansen Research Institute, Ethiopia

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2021
• Primary Completion (Actual): February 1, 2022
• Study Completion (Actual): February 1, 2022

Study Registration Dates

• First Submitted: June 4, 2018
• First Submitted That Met QC Criteria: June 25, 2018
• First Posted (Actual): June 27, 2018

Study Record Updates

• Last Update Posted (Actual): August 19, 2022
• Last Update Submitted That Met QC Criteria: August 18, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Lymphatic Diseases; Eye Diseases; Vector Borne Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Parasitic Diseases; Conjunctivitis; Conjunctival Diseases; Corneal Diseases; Spirurida Infections; Secernentea Infections; Nematode Infections; Helminthiasis; Lymphedema; Chlamydiaceae Infections; Eye Infections, Bacterial; Eye Infections; Chlamydia Infections; Conjunctivitis, Bacterial; Filariasis; Elephantiasis, Filarial; Elephantiasis; Trachoma; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Anthelmintics; Antiplatyhelmintic Agents; Anticestodal Agents; Azithromycin; Ivermectin; Albendazole
• Other Study ID Numbers: 11985

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No