Triple Combinations Against Hookworm Infections in Lao (Tricombi)

May 7, 2018 updated by: Jennifer Keiser, Swiss Tropical & Public Health Institute

Different Drug Combinations Against Hookworm Infection in School-aged Children in the Lao People's Democratic Republic, a Single Blind, Randomised Controlled Trial

More than one billion people are infected with soil-transmitted helminths (STH, A. lumbricoides, hookworm or Trichuris trichiura). Preventive chemotherapy - i.e. annual or biannual treatment of at-risk populations with albendazole or mebendazole is the current strategy against STH. However, the efficacy of both drugs is only moderate against hookworm and low against T. trichiura. For increasing the efficacy and to avoid drug resistance, new drugs or the combination of different drugs is the way forward.

In this randomised controlled trial, we assess the efficacy (based on cure rates) of different drug combinations in school-aged children in Lao. 420 hookworm positive children will be treated: 140 with albendazole-oxantel pamoate, 140 with albendazole-pyrantel pamoate-oxantel pamoate treatment arms, 70 with pyrantel pamoate-oxantel pamoate and 70 with mebendazole-pyrantel pamoate-oxantel pamoate. Two stool samples will be collected at baseline and follow-up (14-21 days after treatment) and analysed with Kato-Katz.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

More than one billion people are infected with A. lumbricoides, hookworm or Trichuris trichiura, the so-called soil-transmitted helminths (STH). Preventive chemotherapy - i.e. annual or biannual treatment of at-risk populations, is the current strategy against STH advocated by the World Health Organization. However, the currently used drugs albendazole and mebendazole have only moderate efficacy against hookworm and low against T. trichiura. The main challenge is their temporal decrease in efficacy, which might be associated with drug resistance, as it was shown in veterinary medicine. For increasing the efficacy and to avoid drug resistance, new drugs or the combination of different drugs is the way forward.

The primary objective of this study is to assess the efficacy (based on cure rates [CR]) of the three combinations, i.e. albendazole-oxantel pamoate, pyrantel pamoate-oxantel pamoate and albendazole-pyrantel pamoate-oxantel pamoate in school-aged children infected with hookworms in Laos. Secondary objectives include; i) a proof of concept, investigating the difference between the two triple combinations albendazole-pyrantel pamoate-oxantel pamoate versus mebendazole-pyrantel pamoate-oxantel pamoate (based on CRs), ii) egg reduction rates (ERR) against hookworm and ERRs/CRs against A. lumbricoides and T. trichiura and iii) tolerability of the 4 combinations.

Two stool samples will be collected from school-aged children (age 6-15) at baseline. 420 hookworm positive children will be treated: 140 with albendazole-oxantel pamoate, 140 with albendazole-pyrantel pamoate-oxantel pamoate, 70 with pyrantel pamoate-oxantel pamoate and 70 with mebendazole-pyrantel pamoate-oxantel pamoate treatment arms The medical history of the participating children will be assessed with a standardized questionnaire, in addition to a clinical examination carried out by the study physician on the treatment day. Children will be interviewed before treatment for clinical symptoms and 3 and 24 hours 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. All stool samples will be examined with duplicated Kato-Katz thick smears.

Study Type

Interventional

Enrollment (Actual)

420

Phase

  • Phase 4

Contacts and Locations

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

Study Locations

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

4 years to 13 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Written informed consent signed by parents and/or legal representative; and a verbal assent (children <12 years) or signed assent (children ≥12 years), according to Lao regulations.
  • Able and willing to be examined by a study physician at the beginning of the study.
  • Able and willing to provide two stool samples at the beginning (baseline) and two to three weeks after treatment (follow-up).
  • Positive for hookworm eggs in the stool.
  • Absence of major systemic illnesses, e.g. diabetes, severe anemia as assessed by a medical doctor, upon initial clinical assessment.
  • No known or reported history of chronical illness as cancer, diabetes, chronic heart, liver or renal disease.
  • No recent anthelminthic treatment (within past 4 weeks).
  • No known allergy to study medications (e.g. albendazole, mebendazole, pyrantel pamoate, oxantel pamoate).
  • Negative pregnancy test (girls ≥12 years)

Exclusion Criteria:

  • No written informed consent by parents and/or legal representative and no verbal assent (children <12 years) or signed assent (children ≥12 years).
  • Presence of major systemic illnesses, e.g. diabetes, severe anemia as assessed by a medical doctor, upon initial clinical assessment.
  • History of acute or severe chronic disease.
  • Recent use of anthelminthic drug (within past 4 weeks).
  • Attending other clinical trials during the study.
  • Negative diagnostic result for hookworm eggs in the stool.
  • Positive pregnancy test (girls ≥12 years)

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
Active Comparator: Albendazole triple combi
Albendazole (400 mg) + pyrantel pamoate (20 mg/kg) + oxantel pamoate (20 mg/kg)
Drug: Albendazole
Albendazole (400 mg) from Janssen, donated by the World Health Organization
Drug: Pyrantel Pamoate
Pyrantel pamoate (20 mg/kg), will be purchased by the World Health Organization
Drug: Oxantel Pamoate
Oxantel pamoate (20mg/kg) will be produced by the University of Basel
Experimental: Pyrantel pamoate double combi
Pyrantel pamoate (20 mg/kg) + oxantel pamoate (20 mg/kg)
Drug: Pyrantel Pamoate
Pyrantel pamoate (20 mg/kg), will be purchased by the World Health Organization
Drug: Oxantel Pamoate
Oxantel pamoate (20mg/kg) will be produced by the University of Basel
Experimental: Albendazole double combi
Albendazole (400 mg) + oxantel pamoate (20 mg/kg)
Drug: Albendazole
Albendazole (400 mg) from Janssen, donated by the World Health Organization
Drug: Oxantel Pamoate
Oxantel pamoate (20mg/kg) will be produced by the University of Basel
Experimental: Mebendazole triple combi
Mebendazole (500mg) + pyrantel pamoate (20 mg/kg) + oxantel pamoate (20 mg/kg)
Drug: Pyrantel Pamoate
Pyrantel pamoate (20 mg/kg), will be purchased by the World Health Organization
Drug: Oxantel Pamoate
Oxantel pamoate (20mg/kg) will be produced by the University of Basel
Drug: Mebendazole
Mebendazole (500 mg) from GlaxoSmithKline, donated by the World Health Organization

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cure rates of three drug combinations
Time Frame: 14-21 days after treatment
to comparatively assess the efficacy (based on cure rates, CR) i) albendazole-oxantel pamoate, ii) pyrantel pamoate-oxantel pamoate, iii) albendazole-pyrantel pamoate-oxantel pamoate in school-aged children infected with hookworms.
14-21 days after treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cure rates against hookworm of the two triple combinations
Time Frame: 14-21 days after treatment
To assess the CRs against hookworm of albendazole-pyrantel pamoate-oxantel pamoate versus mebendazole-pyrantel pamoate-oxantel pamoate (proof of concept)
14-21 days after treatment
Egg reduction rates (ERR) against hookworm and ERRs/CRs against A. lumbricoides and T. trichiura
Time Frame: 14-21 days after treatment
Assessing the egg reduction rates (ERR) against hookworm and ERRs and cure rates (CR) against A. lumbricoides and T. trichiura
14-21 days after treatment
Incidence of adverse events 3 and 24 hours after treatment
Time Frame: 3 and 24 hours after treatment
Participants will be interviewed using a standardized questionnaire, before treatment for clinical symptoms and 3 and 24 hours after treatment about the occurrence of adverse events.
3 and 24 hours after treatment

Collaborators and Investigators

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

Sponsor

Swiss Tropical & Public Health Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

September 27, 2017

Primary Completion (Actual)

November 17, 2017

Study Completion (Actual)

December 1, 2017

Study Registration Dates

First Submitted

September 6, 2017

First Submitted That Met QC Criteria

September 8, 2017

First Posted (Actual)

September 11, 2017

Study Record Updates

Last Update Posted (Actual)

May 8, 2018

Last Update Submitted That Met QC Criteria

May 7, 2018

Last Verified

May 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TRICOMBI01032017

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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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