Efficacy, Safety and Acceptability of Ivermectin ODT in PSAC (Iverped)

April 19, 2024 updated by: Jennifer Keiser

Efficacy, Safety and Acceptability of Ascending Doses of Ivermectin in Combination With Albendazole for Trichuris Trichiura Infections in Preschool-aged Children: a Single-blind Randomised Controlled Dose-ranging Trial

This study is a single-blind randomized controlled dose-ranging trial aiming at providing evidence on the on the optimal dose of co-administered ivermectin and albendazole in terms of efficacy, safety and acceptability in preschool-aged children (PSAC; aged 2-5 years) infected with whipworm (Trichuris trichiura) on Pemba Island, Tanzania. Additionally, the pharmacokinetics of the newly developed ODTs and the standard ivermectin tablets (Stromectol®) will be compared in this age group.

As measure of efficacy of the treatment the cure rate (percentage of egg-positive participants at baseline who become egg-negative after treatment) will be determined 14-21 days post-treatment.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This study is a single-blind randomized controlled dose-ranging trial aiming at providing evidence on the optimal dose of co-administered ivermectin and albendazole in terms of efficacy, safety and acceptability in preschool-aged children (PSAC; aged 2-5 years) infected with whipworm (Trichuris trichiura) on Pemba Island, Tanzania. Additionally, the pharmacokinetics of the newly developed ODTs and the standard ivermectin tablets (Stromectol®) will be compared in this age group.

The primary objective of the trial is to comparatively assess the efficacy in terms of cure rate (CR) against T. trichiura infections among PSAC receiving different doses of ivermectin.

The secondary objectives of the trial are to compare the egg reduction rates (ERRs) of the treatment regimens against T. trichiura, to determine the CRs and ERRs of the drugs in study participants co-infected with A. lumbricoides and hookworm, and to evaluate the safety and tolerability of the treatment regimens.

In addition, this study aims to characterize population pharmacokinetics of the ivermectin ODTs compared to standard tablets in T. trichiura infected individuals, and to assess the acceptability of the treatments.

After obtaining informed consent from parents and/or caregivers, the medical history of the participants will be assessed with a standardized questionnaire, in addition to a clinical examination carried out by the study physician before treatment. Enrollment will be based on two stool samples, which will be collected, if possible, on two consecutive days or otherwise within a maximum of 5 days. All stool samples will be examined with duplicated Kato-Katz thick smears by experienced laboratory technicians.

Randomization of participants into the six treatment arms will be stratified according to intensity of infection and age. All participants will be interviewed before treatment, and at 3 and 24 hours and 14-21 days after treatment about the occurrence of adverse events. The efficacy of the treatment will be determined 14-21 days post-treatment by collecting another two stool samples.

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 participants at baseline who become egg-negative after treatment. Differences among CRs between treatment arms will be analysed using crude and adjusted logistic regression modeling (adjustment for age, sex and weight). 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.Using the DoseFinding package of the statistical software environment R, Emax models will be implemented to predict the dose-response curves based on CRs and ERRs.

Adverse events will be compiled into frequency tables and compared between treatment groups using descriptive summary statistics.

Study Type

Interventional

Enrollment (Estimated)

210

Phase

  • Phase 2

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

  • Tanzania
      • Chake Chake, Tanzania
        • Public Health Laboratory Ivo de Carneri
        • 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:

  • individuals aged 2-5 years (24-71 months; confirmed by birth certificate or similar document)
  • having given written informed consent signed by parents/caregivers
  • being able and willing to provide two stool samples at baseline and at follow-up assessment (14-21 days)
  • having at least two out of four Kato-Katz slides positive for T. trichiura at baseline
  • being able and willing to be examined by a study physician before and after treatment

Exclusion Criteria:

  • presence or signs of major systemic illness, e.g. fever (temporal body temperature of >38.0°C), severe anaemia (haemoglobin level of <70 g/l)
  • history of severe acute disease or unmanaged, severe chronic disease (i.e., condition is not as therapeutically controlled as necessary)
  • use of anthelminthic drugs during study period
  • known allergy to study medication (i.e., ivermectin or albendazole)
  • being prescribed or taking concomitantly medication with known contraindications or drug interactions with the study medication
  • concurrent participation in other clinical trials

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
Placebo Comparator: Arm A: IVM ODT Placebo
Placebo for ivermectin (oro-dispersible tablets) and albendazole (Zentel®, 1 tablet of 400 mg) administered orally at day 0
Drug: Albendazole 400 mg Oral Tablet
Tablets of 400 mg albendazole
Other Names:
  • Zentel®
Drug: Placebo IVM ODT
Placebo for ivermectin ODT
Experimental: Arm B: IVM ODT 100 µg/kg
Combination therapy of ivermectin (100 µg/kg using oro-dispersible tablets of 1.5 mg) and albendazole (Zentel®, 1 tablet of 400 mg) administered orally at day 0
Drug: Albendazole 400 mg Oral Tablet
Tablets of 400 mg albendazole
Other Names:
  • Zentel®
Drug: Ivermectin 1.5 mg ODT
Oro-dispersible tablets of 1.5 mg ivermectin
Experimental: Arm C: IVM ODT 200 µg/kg
Combination therapy of ivermectin (200 µg/kg using oro-dispersible tablets of 1.5 mg) and albendazole (Zentel®, 1 tablet of 400 mg) administered orally at day 0
Drug: Albendazole 400 mg Oral Tablet
Tablets of 400 mg albendazole
Other Names:
  • Zentel®
Drug: Ivermectin 1.5 mg ODT
Oro-dispersible tablets of 1.5 mg ivermectin
Experimental: Arm D: IVM ODT 300 µg/kg
Combination therapy of ivermectin (300 µg/kg using oro-dispersible tablets of 1.5 mg) and albendazole (Zentel®, 1 tablet of 400 mg) administered orally at day 0
Drug: Albendazole 400 mg Oral Tablet
Tablets of 400 mg albendazole
Other Names:
  • Zentel®
Drug: Ivermectin 1.5 mg ODT
Oro-dispersible tablets of 1.5 mg ivermectin
Experimental: Arm E: IVM ODT 400 µg/kg
Combination therapy of ivermectin (400 µg/kg using oro-dispersible tablets of 1.5 mg) and albendazole (Zentel®, 1 tablet of 400 mg) administered orally at day 0
Drug: Albendazole 400 mg Oral Tablet
Tablets of 400 mg albendazole
Other Names:
  • Zentel®
Drug: Ivermectin 1.5 mg ODT
Oro-dispersible tablets of 1.5 mg ivermectin
Active Comparator: Arm F: IVM standard tablets
Combination therapy of ivermectin (Stromectol®, 200 µg/kg using tablets of 3 mg) and albendazole (Zentel®, 1 tablet of 400 mg) administered orally at day 0
Drug: Albendazole 400 mg Oral Tablet
Tablets of 400 mg albendazole
Other Names:
  • Zentel®
Drug: Ivermectin 3 mg Oral Tablet
Tablets of 3 mg ivermectin
Other Names:
  • Stromectol®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cure rate (CR) against T. trichiura
Time Frame: 14-21 days post-treatment
The CR will be calculated as the proportion of participants converting from being egg-positive pre-treatment to egg-negative post-treatment.
14-21 days post-treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Egg reduction rate (ERR) against T. trichiura
Time Frame: 14-21 days post-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 post-treatment
Cure rate (CR) against A. lumbricoides
Time Frame: 14-21 days post-treatment
The CR will be calculated as the proportion of participants converting from being egg-positive pre-treatment to egg-negative post-treatment.
14-21 days post-treatment
Egg reduction rate (ERR) against A. lumbricoides
Time Frame: 14-21 days post-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 post-treatment
Cure rate (CR) against Hookworm
Time Frame: 14-21 days post-treatment
The CR will be calculated as the proportion of participants converting from being egg-positive pre-treatment to egg-negative post-treatment.
14-21 days post-treatment
Egg reduction rate (ERR) against Hookworm
Time Frame: 14-21 days post-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 post-treatment
Number of participants reporting adverse events (AEs)
Time Frame: 3 hours, 24 hours and 14-21 days post-treatment
Participants will be monitored at the site for 3 hours following treatment for any acute AEs and reassessment will be done at 24h post-treatment. In addition, participants will be interviewed 3 and 24 hours after treatment and retrospectively at days 14-21 about the occurrence of AEs.
3 hours, 24 hours and 14-21 days post-treatment

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Blood concentration of ivermectin
Time Frame: 0 to 24 hours post-treatment
For characterization of population pharmacokinetics (PK), ivermectin concentration will be quantified using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Drug concentrations will be calculated by interpolation from a calibration curve with a lower limit of quantification of 1-5 ng/ml.
0 to 24 hours post-treatment
Acceptability of ODT assessed by visual analogue scale (0-100 mm)
Time Frame: 15 min post-treatment
To determine the acceptability of ivermectin ODTs compared to standard tablets, the palatability of each formulation will be rated by children aged 4-5 years using a visual analogue scale with continuous scores from 0 mm (worst taste) to 100 mm (best taste).
15 min post-treatment

Collaborators and Investigators

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

Sponsor

Jennifer Keiser

Collaborators

Public Health Laboratory Ivo de Carneri

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 (Estimated)

June 1, 2024

Primary Completion (Estimated)

August 1, 2024

Study Completion (Estimated)

August 1, 2024

Study Registration Dates

First Submitted

December 14, 2023

First Submitted That Met QC Criteria

December 14, 2023

First Posted (Actual)

December 28, 2023

Study Record Updates

Last Update Posted (Actual)

April 22, 2024

Last Update Submitted That Met QC Criteria

April 19, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Iverped_1

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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