Efficacy of Ivermectin-albendazole vs Albendazole Alone in School-aged Children Infected With Trichuris Trichiura (FACEITeffic)

April 9, 2024 updated by: Jennifer Keiser

Efficacy of the Combination Ivermectin and Albendazole vs Albendazole Alone in School-aged Children Infected With Trichuris Trichiura: a Randomized Controlled Trial

The goal of this parallel open-label randomized controlled superiority trial is to demonstrate that co-administered ivermectin (200 µg/kg) plus albendazole (400 mg) is superior to albendazole (400 mg) monotherapy in terms of cure rates against Trichuris trichiura infections assessed by Kato-Katz at 14-21 days post-treatment in individuals aged 6-12 years.

The main questions it aims to answer are:

  • Is single oral dose combined ivermectin-albendazole superior to albendazole alone in terms of cure rates and egg reduction rates against T. trichiura infections in children aged 6-12 years in Uganda?
  • Is single oral dose combined ivermectin-albendazole superior to albendazole alone in terms of cure rates and egg reduction rates against co-infecting soil-transmitted helminth infections such as Ascaris lumbricoides and hookworm in children aged 6-12 years in Uganda?
  • Is single oral dose combined ivermectin-albendazole as tolerable and safe as albendazole monotherapy in children aged 6-12 years in Uganda?

Participants will be asked to provide two stool samples at baseline that will be subjected to microscopic analysis using the Kato-Katz thick smear technique for detection of soil-transmitted helminth eggs. T. trichiura-infected participants will be:

  • clinically examined for general health, anthropometric parameters including height and weight as well as temperature
  • randomly assigned to either receive one single oral dose of combined ivermectin and albendazole or albendazole monotherapy
  • checked for any potential adverse events and will undergo a brief questionnaire on specific symptoms 3h after drug administration
  • asked to provide another two stool samples to be microscopically examined for helminth eggs 14-21 days post-treatment Researchers will compare individuals treated with ivermectin-albendazole and albendazole alone to see if the proportion of T. trichiura egg-negative individuals and/or reduction in egg counts differs between these two groups 14-21 days after treatment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In view that efficacy of co-administered ivermectin (IVM) and albendazole (ALB) has been found to vary between different settings the rationale of this parallel open-label randomized controlled superiority trial is to provide evidence on the efficacy of co-administered ivermectin and albendazole compared to albendazole monotherapy in school-aged children aged 6-12 years against infection with T. trichiura in Uganda.

Our primary objective is to demonstrate superiority of

  1. Arm A: single dose of ivermectin (200 µg/kg, 3 mg tablets according to weight) / single dose of albendazole (400 mg tablet) combination, compared to
  2. Arm B: single dose of albendazole (400 mg tablet)

in terms of cure rate (CR) against T. trichiura infections in school-aged children aged 6-12 years assessed at 14-21 days post-treatment by Kato-Katz microscopy.

The secondary objectives of the trial are:

  1. to determine the egg reduction rates (ERRs) of ivermectin/albendazole combination therapy compared to albendazole monotherapy against T. trichiura
  2. to determine the CRs and ERRs of the study drugs against Ascaris lumbricoides and hookworm in co-infected participants
  3. to evaluate the safety and tolerability of the treatment

The study will be implemented as a school-based study and children aged 6-12 years from two primary schools in Kabale district, southwestern Uganda will be invited for parasitological examination after obtaining informed consent from parents/caregivers and assent by the minor participants. Two stool samples will be collected, when possible, on two consecutive days. Children found to be infected with T. trichiura based on quadruplicate Kato-Katz thick smear readings will be enrolled into the actual trial. The medical history of the participants will be assessed with a standardized questionnaire, in addition to a clinical examination carried out by the study nurse/physician before treatment.

All participants will be interviewed before treatment and after 3 and 24 hours (active surveillance) for the occurrence of adverse events (AEs). Participants and their caregivers will be told that any potential AEs happening between 24 hours and the respective follow-up time point for stool collection should be reported to the local village health team (VHT) members, which will be trained to handle the situation by taking the participant to a health facility for timely treatment, or to local health workers directly.

The efficacy of the treatment will be determined at 14-21 days post-treatment by collecting another two stool samples.

At both, baseline and follow-up (14-21 days post treatment) a portion of stool (1.5-2 g) from all participants identified with T. trichiura infections will be preserved in 95% ethanol, shipped to a reference laboratory in Switzerland and subjected to amplicon deep sequencing for characterization of T. trichiura strains and investigation of potential resistance markers.

Study participants eligible for treatment will be randomly assigned to one of the two treatment arms stratified by 2 levels of baseline infection intensity (light: 1-999 EPG, and moderate plus heavy: ≥ 1000 EPG T. trichiura infections).

The primary analysis will include all participants with primary end point data (available case analysis). Supplementary, a per-protocol analysis will be conducted. CRs will be calculated as the percentage of egg-positive subjects at baseline who become egg-negative after treatment. Differences among CRs (between treatment arms) will be analyzed by using crude and adjusted logistic regression modeling.

Geometric and arithmetic mean egg counts will be calculated for the different treatment arms before and after treatment to assess the corresponding ERRs. Bootstrap resampling method with 5,000 replicates will be used to calculate 95% confidence intervals (CIs) for differences in ERRs.

Study Type

Interventional

Enrollment (Actual)

161

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Uganda
      • Kampala, Uganda, P.O.Box 1661
        • Vector Borne & Neglected Tropical Disease Control Division, Ministry of Health
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Written informed consent for participation signed from caregivers; and written assent by participants.
  • Agree to comply with study procedures, including provision of two stool samples at the beginning (baseline) and at follow-up assessment 14-21 days after treatment.
  • Willing to be examined by a study nurse/physician prior to treatment.
  • At least two slides of the quadruple Kato-Katz thick smears positive for T. trichiura.

Exclusion Criteria:

  • Presence or signs of major systemic illnesses, e.g. body temperature ≥ 38°C, clinical malaria (fever + positive RDT) upon initial clinical assessment.
  • Recent use of anthelmintic drug (within past 4 weeks).
  • Attending other experimental research studies.
  • Known allergy to study medications (i.e. benzimidazole or ivermectin).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: IVM (200 µg/kg) + ALB (400 mg)
A single tablet of albendazole (400mg) plus 200 µg/kg of ivermectin, provided as single oral dose.
Drug: IVM (200 µg/kg) + ALB (400 mg)
World Health Organization Pre-Qualification (WHO PQ) recommended ivermectin 3mg tablets will be used together with albendazole 400mg tablets as provided by WHO for Neglected Tropical Disease (NTD) programs.
Other Names:
  • Zentel® and Stromectol®, Ivermectin Tablet 3mg
Active Comparator: ALB (400mg)
A single tablet of albendazole (400mg), provided as single oral dose.
Drug: ALB (400mg)
Albendazole 400mg manufactured and donated by GlaxoSmithKline (GSK) to WHO
Other Names:
  • Zentel®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants T. Trichiura Egg Negative Post-Treatment (Cured)
Time Frame: 14-21 days after treatment
The conversion from being egg positive pre-treatment to egg negative post-treatment, or cure rate (CR).
14-21 days after treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Egg Reduction Rate (ERR) against T. Trichiura
Time Frame: 14-21 days after treatment
Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. Geometric and arithmetic mean egg counts will be calculated for the two treatment arms before and after treatment to assess the corresponding ERRs.
14-21 days after treatment
Number of Participants With Concomitant Soil-transmitted Helminth Infections Egg Negative Post-Treatment (Cured)
Time Frame: 14-21 days after treatment
Number of participants that converted from egg positive with Ascaris lumbricoides and/or hookworm infections to egg negative after 14-21 days.
14-21 days after treatment
Egg-reduction Rates (ERRs) Against Concomitant Soil-transmitted Helminth Infections
Time Frame: 14-21 days after treatment
Percent change in geometric mean eggs per gram of stool from before to after treatment. ERRs will be calculated for Ascaris lumbricoides and hookworm infections as described in outcome 2.
14-21 days after treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jennifer Keiser

Collaborators

Vector Borne & Neglected Tropical Disease Control Division, Ministry of Health, Uganda

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 9, 2023

Primary Completion (Actual)

November 9, 2023

Study Completion (Actual)

November 14, 2023

Study Registration Dates

First Submitted

September 7, 2023

First Submitted That Met QC Criteria

September 7, 2023

First Posted (Actual)

September 14, 2023

Study Record Updates

Last Update Posted (Actual)

April 10, 2024

Last Update Submitted That Met QC Criteria

April 9, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BRCCH PII 2021

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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