HI4T: Albendazole Plus High Dose Ivermectin for Trichuriasis in Pediatric Patients

• Sponsor: Alejandro Krolewiecki (Other)
• Overall Status: Completed
• CT.gov ID: NCT04041453
• Collaborator: Brock University (Other), Universidad Nacional del Centro de la Provincia de Buenos Aires (Other), Universidad Nacional Autonoma de Honduras (Other)
• Enrollment: 176
• Locations: 2
• Arms: 4
• Actual Duration (Months): 4.9
• Patients Per Site: 88
• Patients Per Site Per Month: 17.9

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Trichuris Infection; Helminthiasis	Drug: Ivermectin; Drug: Albendazole	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 176 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Prospective, Parallel-group, Open-label Randomized Controlled Trial of Four Treatment Regimes for Trichuriasis in Pediatric Patients
• Actual Study Start Date: Oct 9, 2019
• Actual Primary Completion Date: Mar 7, 2020
• Actual Study Completion Date: Mar 7, 2020

Arms and Interventions

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: Ivermectin; Ivermectin at 600mcg/kg in addition to albendazole will be provided for 1 or 3 days.; Drug: Albendazole; Albendazole will be provided as an active control or in experimental arms for 1 or 3 days with ivermectin.
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: Ivermectin; Ivermectin at 600mcg/kg in addition to albendazole will be provided for 1 or 3 days.; Drug: Albendazole; Albendazole will be provided as an active control or in experimental arms for 1 or 3 days with ivermectin.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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).

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 14 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	IIET	Oran	Salta	Argentina	4530
2	Universidad Autónoma de Honduras	Tegucigalpa		Honduras

Sponsors and Collaborators

• Alejandro Krolewiecki
• 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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 29, 2018

More Information

Publications

None provided.

• Responsible Party: Alejandro Krolewiecki, Investigador CIC CONICET, Universidad Nacional de Salta
• ClinicalTrials.gov Identifier: NCT04041453
• Other Study ID Numbers: 01-2019
• First Posted: Aug 1, 2019
• Last Update Posted: Jul 29, 2020
• Last Verified: Jul 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Alejandro Krolewiecki, Investigador CIC CONICET, Universidad Nacional de Salta: TRICHURIS; STH; IVERMECTIN; ALBENDAZOLE
• Additional relevant MeSH terms: Helminthiasis; Trichuriasis; Ivermectin; Albendazole

Study Results

Participant Flow

Arm/Group Title	Albendazole 400mg	Albendazole/Ivermectin	Albendazole 400mg x 3	Albendazole/Ivermectin x 3
Arm/Group Description	Albendazole 400mg in single dose	Combination of albendazole 400mg + ivermectin 600mcg/kg in single dose.	Albendazole 400mg/day for 3 consecutive days.	Combination of albendazole 400mg/day + ivermectin 600mcg/kg/day for 3 consecutive days
Period Title: Overall Study
STARTED	38	57	23	58
Safety Population	38	56	23	58
COMPLETED	24	35	18	40
NOT COMPLETED	14	22	5	18

Baseline Characteristics

Arm/Group Title	Albendazole 400mg	Albendazole/Ivermectin	Albendazole 400mg x 3	Albendazole/Ivermectin x 3	Total
Arm/Group Description	Albendazole 400mg in single dose	Combination of albendazole 400mg + ivermectin 600mcg/kg in single dose.	Albendazole 400mg/day for 3 consecutive days	Combination of albendazole 400mg/day + ivermectin 600mcg/kg/day for 3 consecutive days	Total of all reporting groups
Overall Participants	38	57	23	58	176
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.5 (2.6)	8.0 (2.2)	8.5 (2.0)	8.0 (2.2)	8.2 (2.3)
Sex: Female, Male (Count of Participants)
Female	19 50%	24 42.1%	13 56.5%	30 51.7%	86 48.9%
Male	19 50%	33 57.9%	10 43.5%	28 48.3%	90 51.1%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%

Outcome Measures

1. Primary Outcome

Title	Cure Rate
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Albendazole 400mg	Albendazole/Ivermectin	Albendazole 400mg x3	Albendazole/Ivermectin x 3
Arm/Group Description	Albendazole 400mg in single dose	Combination of albendazole 400mg + ivermectin 600mcg/kg in single dose.	Albendazole 400mg/day for 3 consecutive days.	Combination of albendazole 400mg/day + ivermectin 600mcg/kg/day for 3 consecutive days
Measure Participants	24	35	18	40
Count of Participants [Participants]	1 2.6%	31 54.4%	6 26.1%	40 69%

2. Secondary Outcome

Title	Egg Change Rate
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Albendazole 400mg	Albendazole/Ivermectin	Albendazole x 3	Albendazole/Ivermectin x 3
Arm/Group Description	Albendazole 400mg in single dose	Albendazole 400mg + ivermectin 600mcg/kg in single dose.	Albendazole 400mg/day for 3 consecutive days.	Combination of albendazole 400mg/day + ivermectin 600mcg/kg/day for 3 consecutive days
Measure Participants	24	35	18	40
Number [Percent change]	50	97	72	100

3. Secondary Outcome

Title	Beta Tubulin Resistance
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Adverse events were collected since the subject's enrollment until end of study participation (Day 21).
Arm/Group Title	Albendazole 400mg		Albendazole/Ivermectin		Albendazole 400mg x3		Albendazole/Ivermectin x 3
Arm/Group Description	Albendazole 400mg in single dose		Combination of albendazole 400mg + ivermectin 600mcg/kg in single dose		Albendazole 400mg/day in 3 consecutive days		Combination of albendazole 400mg/day + ivermectin 600mcg/kg/day in 3 consecutive days
All Cause Mortality
	Albendazole 400mg		Albendazole/Ivermectin		Albendazole 400mg x3		Albendazole/Ivermectin x 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/56 (0%)		0/23 (0%)		0/58 (0%)
Serious Adverse Events
	Albendazole 400mg		Albendazole/Ivermectin		Albendazole 400mg x3		Albendazole/Ivermectin x 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/56 (0%)		0/23 (0%)		0/58 (0%)
Other (Not Including Serious) Adverse Events
	Albendazole 400mg		Albendazole/Ivermectin		Albendazole 400mg x3		Albendazole/Ivermectin x 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		10/56 (17.9%)		7/23 (30.4%)		10/58 (17.2%)
Eye disorders
Photophobia	0/38 (0%)	0	0/56 (0%)	0	2/23 (8.7%)	2	0/58 (0%)	0
Gastrointestinal disorders
Abdominal pain	0/38 (0%)	0	4/56 (7.1%)	4	2/23 (8.7%)	2	4/58 (6.9%)	4
Vomiting	0/38 (0%)	0	0/56 (0%)	0	0/23 (0%)	0	1/58 (1.7%)	1
Diarrhea	0/38 (0%)	0	1/56 (1.8%)	1	0/23 (0%)	0	0/58 (0%)	0
General disorders
Headache	0/38 (0%)	0	5/56 (8.9%)	5	2/23 (8.7%)	2	4/58 (6.9%)	4
Skin and subcutaneous tissue disorders
Pruritus	0/38 (0%)	0	0/56 (0%)	0	1/23 (4.3%)	1	1/58 (1.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.