Helminthiasis, Trichuris Infection
Conditions
Keywords
TRICHURIS, STH, IVERMECTIN, ALBENDAZOLE
Brief summary
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
Interventions
DRUGIvermectin
Ivermectin at 600mcg/kg in addition to albendazole will be provided for 1 or 3 days.
DRUGAlbendazole
Albendazole will be provided as an active control or in experimental arms for 1 or 3 days with ivermectin.
Sponsors
Alejandro Krolewiecki
Brock University
Universidad Nacional del Centro de la Provincia de Buenos Aires
Universidad Nacional Autonoma de Honduras
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Years to 14 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cure Rate | 21 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Egg Change Rate | 21 days | 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). |
| Beta Tubulin Resistance | 21days | 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. |
Countries
Argentina, Honduras
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Albendazole 400mg Albendazole 400mg in single dose | 38 |
| Albendazole/Ivermectin Combination of albendazole 400mg + ivermectin 600mcg/kg in single dose. | 57 |
| Albendazole 400mg x 3 Albendazole 400mg/day for 3 consecutive days | 23 |
| Albendazole/Ivermectin x 3 Combination of albendazole 400mg/day + ivermectin 600mcg/kg/day for 3 consecutive days | 58 |
| Total | 176 |
Baseline characteristics
| Characteristic | Albendazole 400mg | Albendazole/Ivermectin | Albendazole 400mg x 3 | Albendazole/Ivermectin x 3 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 8.5 years STANDARD_DEVIATION 2.6 | 8.0 years STANDARD_DEVIATION 2.2 | 8.5 years STANDARD_DEVIATION 2 | 8.0 years STANDARD_DEVIATION 2.2 | 8.2 years STANDARD_DEVIATION 2.3 |
| Race and Ethnicity Not Collected | — | — | — | — | 0 Participants |
| Sex: Female, Male Female | 19 Participants | 24 Participants | 13 Participants | 30 Participants | 86 Participants |
| Sex: Female, Male Male | 19 Participants | 33 Participants | 10 Participants | 28 Participants | 90 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 38 | 0 / 56 | 0 / 23 | 0 / 58 |
| other Total, other adverse events | 0 / 38 | 10 / 56 | 7 / 23 | 10 / 58 |
| serious Total, serious adverse events | 0 / 38 | 0 / 56 | 0 / 23 | 0 / 58 |
Outcome results
Primary
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.
Time frame: 21 days
Population: The follow-up visit for efficacy assessment on Day 21 post-drug administration was not conducted in 52 subjects due to the outbreak of COVID-19 pandemic in Honduras which precluded completion of study visits in March 2020.~Additional 7 subjects did not complete the study: 1 did not take the study medication, and 6 subjects were lost to follow up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Albendazole 400mg | Cure Rate | 1 Participants |
| Albendazole/Ivermectin | Cure Rate | 31 Participants |
| Albendazole 400mg x3 | Cure Rate | 6 Participants |
| Albendazole/Ivermectin x 3 | Cure Rate | 40 Participants |
Secondary
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.
Time frame: 21days
Secondary
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).
Time frame: 21 days
Population: The follow-up visit for efficacy assessment on Day 21 post-drug administration was not conducted in 52 subjects due to the outbreak of COVID-19 pandemic in Honduras which precluded completion of study visits in March 2020.~Additional 7 subjects did not complete the study: 1 did not take the study medication, and 6 subjects were lost to follow up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Albendazole 400mg | Egg Change Rate | 50 Percent change |
| Albendazole/Ivermectin | Egg Change Rate | 97 Percent change |
| Albendazole 400mg x3 | Egg Change Rate | 72 Percent change |
| Albendazole/Ivermectin x 3 | Egg Change Rate | 100 Percent change |