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CompletedNCT03278431TricombiUpdated May 8, 2018

Triple Combinations Against Hookworm Infections in Lao

A Phase 4 interventional study of Albendazole and Pyrantel Pamoate in Hookworm Infection, sponsored by Swiss Tropical & Public Health Institute. Completed at 1 site in Lao People's Democratic Republic. Open to participants aged 6 Years to 15 Years. Per ClinicalTrials.gov, last updated 2018-05-08.

Sponsored by Swiss Tropical & Public Health Institute · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
420
Allocation
Randomized
Ages
6 Years to 15 Years
Sex
All
01

Study summary

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.

Read the 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.

02

Conditions studied

03

Who can participate

Ages eligible
6 Years to 15 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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)
04

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Participant)
Enrollment
420 participants (actual)

Study arms

  • Active comparator
    Albendazole triple combi

    Albendazole (400 mg) + pyrantel pamoate (20 mg/kg) + oxantel pamoate (20 mg/kg)

    Drug: Albendazole · Drug: Pyrantel Pamoate · Drug: Oxantel Pamoate

  • Experimental
    Pyrantel pamoate double combi

    Pyrantel pamoate (20 mg/kg) + oxantel pamoate (20 mg/kg)

    Drug: Pyrantel Pamoate · Drug: Oxantel Pamoate

  • Experimental
    Albendazole double combi

    Albendazole (400 mg) + oxantel pamoate (20 mg/kg)

    Drug: Albendazole · Drug: Oxantel Pamoate

  • Experimental
    Mebendazole triple combi

    Mebendazole (500mg) + pyrantel pamoate (20 mg/kg) + oxantel pamoate (20 mg/kg)

    Drug: Pyrantel Pamoate · Drug: Oxantel Pamoate · Drug: Mebendazole

Interventions

  • DrugAlbendazole

    Albendazole (400 mg) from Janssen, donated by the World Health Organization

  • DrugPyrantel Pamoate

    Pyrantel pamoate (20 mg/kg), will be purchased by the World Health Organization

  • DrugOxantel Pamoate

    Oxantel pamoate (20mg/kg) will be produced by the University of Basel

  • DrugMebendazole

    Mebendazole (500 mg) from GlaxoSmithKline, donated by the World Health Organization

05

What researchers measure

Primary outcomes

  1. Cure rates of three drug combinations

    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.

    Time frame: 14-21 days after treatment

Secondary outcomes

  1. Cure rates against hookworm of the two triple combinations

    To assess the CRs against hookworm of albendazole-pyrantel pamoate-oxantel pamoate versus mebendazole-pyrantel pamoate-oxantel pamoate (proof of concept)

    Time frame: 14-21 days after treatment

  2. Egg reduction rates (ERR) against hookworm and ERRs/CRs against A. lumbricoides and T. trichiura

    Assessing the egg reduction rates (ERR) against hookworm and ERRs and cure rates (CR) against A. lumbricoides and T. trichiura

    Time frame: 14-21 days after treatment

  3. Incidence of adverse events 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.

    Time frame: 3 and 24 hours after treatment

06

Study locations

1 site
  • Nambak District Hospital
    Luang Prabang, 0604, Lao People's Democratic Republic
07

References and documents

Publications

  • Moser W, Sayasone S, Xayavong S, Bounheuang B, Puchkov M, Huwyler J, Hattendorf J, Keiser J. Efficacy and tolerability of triple drug therapy with albendazole, pyrantel pamoate, and oxantel pamoate compared with albendazole plus oxantel pamoate, pyrantel pamoate plus oxantel pamoate, and mebendazole plus pyrantel pamoate and oxantel pamoate against hookworm infections in school-aged children in Laos: a randomised, single-blind trial. Lancet Infect Dis. 2018 Jul;18(7):729-737. doi: 10.1016/S1473-3099(18)30220-2. Epub 2018 Apr 16. PubMed 29673735 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03278431
Lead sponsor
Swiss Tropical & Public Health Institute
Responsible party
Jennifer Keiser (Prof, Swiss Tropical & Public Health Institute) — Principal investigator
First posted
Sep 11, 2017
Start date
Sep 27, 2017
Primary completion
Nov 17, 2017
Completion
Dec 1, 2017
Last update
May 8, 2018

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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