Albendazole Plus High Dose Ivermectin for Trichuriasis in Pediatric Patients (HI4T)

Prospective, Parallel-group, Open-label Randomized Controlled Trial of Four Treatment Regimes for Trichuriasis in Pediatric Patients

There are four species of intestinal worms collectively known as soil-transmitted helminthiasis (STH): Ancylostoma duodenale and Necator americanus (hookworms), Ascaris lumbricoides (roundworms), and Trichuris trichiura (whipworms). These parasites affect over two billion people and contribute to significant morbidity and disability, especially in high risk groups, for example children, agricultural workers and pregnant women. In children, STH are associated with impaired nutritional status evidenced by stunting, thinness and underweight.

As is the case in most Latin America, STH are a public health problem in Honduras. The World Health Organization (WHO) informs that more than 2.5 million children (under 15 years of age) in the country are at risk of infection. To control these infections Honduras has established a national deworming program that operates since 2001 but despite these efforts, the prevalence of STH infections remains unacceptably high. This is especially true in rural communities where prevalence can be as high as 70% of the children population.

Ivermectin (IVM) in combination with albendazole (ALB) has demonstrated the capacity to improve efficacy compared to any of these drugs in monotherapy; the efficacy is however, still inadequate in terms of cure rate, although egg reduction rates are significant.

The purpose of the current trial is to assess the safety and efficacy of 3 experimental regimens for the treatment of infections by Trichuris trichiura in children in comparison with the current standard of practice in Mass Drug Administration (MDA) campaigns. The experimental regimens will explore the effect of multiple day regimens and high dose ivermectin.

Treatment arms:

• Group 1: single dose of ALB 400 mg. (active control arm). N:39
• Group 2: single dose ALB 400mg + IVM 600µg/Kg. N: 57
• Group 3: daily dose ALB 400mg for 3 consecutive days. N:24
• Group 4: daily dose ALB 400mg + IVM 600µg for 3 consecutive days. N:57

Total Study Population: 177

Study Overview

• Status: Completed
• Conditions: Helminthiasis; Trichuris Infection
• Intervention / Treatment: Drug: Albendazole; Drug: Ivermectin

• Study Type: Interventional
• Enrollment (Actual): 176
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Salta
    • Oran, Salta, Argentina, 4530
      • IIET
• Honduras
  • Tegucigalpa, Honduras
    • Universidad Autónoma de Honduras

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 10 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Infection with T. trichiura by Kato Katz.
• Body weight >15kg.
• Accepts participation

Exclusion Criteria:

• Albendazole and/or mebendazol treatment in the previous 3 months.
• Allergy to the study drugs
• Acute medical conditions
• Clinical trial participation in the previous 3 months.
• Pregnancy.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Albendazole 400mg; Albendazole 400mg in single dose	Drug: Albendazole; Albendazole will be provided as an active control or in experimental arms for 1 or 3 days with ivermectin.
Experimental: Albendazole/Ivermectin; Combination of albendazole 400mg + ivermectin 600mcg/kg in single dose.	Drug: Albendazole; Albendazole will be provided as an active control or in experimental arms for 1 or 3 days with ivermectin.; Drug: Ivermectin; Ivermectin at 600mcg/kg in addition to albendazole will be provided for 1 or 3 days.
Experimental: Albendazole 400mg x 3; Albendazole 400mg/day for 3 consecutive days	Drug: Albendazole; Albendazole will be provided as an active control or in experimental arms for 1 or 3 days with ivermectin.
Experimental: Albendazole/Ivermectin x 3; Combination of albendazole 400mg/day + ivermectin 600mcg/kg/day for 3 consecutive days	Drug: Albendazole; Albendazole will be provided as an active control or in experimental arms for 1 or 3 days with ivermectin.; Drug: Ivermectin; Ivermectin at 600mcg/kg in addition to albendazole will be provided for 1 or 3 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cure Rate	Number of individuals cured from Trichuris trichiura infection using the duplicate Kato Katz laboratory method on a single sample of fresh stools as the measurement tool. Cure rate is defined as the absence of Trichuris trichiura eggs in post-treatment samples.	21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Egg Change Rate	Calculation details: 100 x (1 - arithmetic mean fecal egg count post-intervention / arithmetic mean fecal egg count pre-intervention) Egg change rate was calculated across all participants, as described in reference: Levecke B et al., PLoS Negl Trop Dis. 2014;8(10).	21 days
Beta Tubulin Resistance	Measurement of the incidence of mutations of tubulin in Trichuris trichiura eggs collected pre and post treatment using molecular biology techniques. This data is not available yet due to the COVID-19 pandemic, but the data will be available and reported in the future. Anticipated reporting date for this outcome measure is estimated by 2021 and will be confirmed once the pandemic is over.	21days

Collaborators and Investigators

• Sponsor: Alejandro Krolewiecki
• Collaborators: Brock University; Universidad Nacional del Centro de la Provincia de Buenos Aires; Universidad Nacional Autonoma de Honduras
• Investigators: Study Director: Alejandro J Krolewiecki, MD, PhD, IIET - Universidad Nacional de Salta

Publications and helpful links

General Publications

• Matamoros G, Sanchez A, Gabrie JA, Juarez M, Ceballos L, Escalada A, Rodriguez C, Marti-Soler H, Rueda MM, Canales M, Lanusse C, Cajal P, Alvarez L, Cimino RO, Krolewiecki A. Efficacy and Safety of Albendazole and High-Dose Ivermectin Coadministration in School-Aged Children Infected With Trichuris trichiura in Honduras: A Randomized Controlled Trial. Clin Infect Dis. 2021 Oct 5;73(7):1203-1210. doi: 10.1093/cid/ciab365.

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2019
• Primary Completion (Actual): March 7, 2020
• Study Completion (Actual): March 7, 2020

Study Registration Dates

• First Submitted: July 22, 2019
• First Submitted That Met QC Criteria: July 31, 2019
• First Posted (Actual): August 1, 2019

Study Record Updates

• Last Update Posted (Actual): July 29, 2020
• Last Update Submitted That Met QC Criteria: July 27, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: IVERMECTIN; TRICHURIS; STH; ALBENDAZOLE
• Additional Relevant MeSH Terms: Infections; Parasitic Diseases; Nematode Infections; Enoplida Infections; Adenophorea Infections; Helminthiasis; Trichuriasis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antiprotozoal Agents; Antiparasitic Agents; Anthelmintics; Antiplatyhelmintic Agents; Anticestodal Agents; Ivermectin; Albendazole
• Other Study ID Numbers: 01-2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: All IPD that underlie results in a publication.
• IPD Sharing Time Frame: After study data analysis completion, with submission for publication to a peer review journal..
• IPD Sharing Access Criteria: Database will be made available through a publication.
• IPD Sharing Supporting Information Type: Analytic Code

Drug and device information, study documents

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