Efficacy and safety of ivermectin and albendazole co-administration in school-aged children and adults infected with Trichuris trichiura: study protocol for a multi-country randomized controlled double-blind trial

Chandni Patel, Eveline Hürlimann, Ladina Keller, Jan Hattendorf, Somphou Sayasone, Said M Ali, Shaali M Ame, Jean T Coulibaly, Jennifer Keiser, Chandni Patel, Eveline Hürlimann, Ladina Keller, Jan Hattendorf, Somphou Sayasone, Said M Ali, Shaali M Ame, Jean T Coulibaly, Jennifer Keiser

Abstract

Background: Soil-transmitted helminthiasis affects almost 2 billion people worldwide in tropical climates. Preventive chemotherapy, using the benzimidazoles (albendazole and mebendazole) is the current main recommended control strategy. Nevertheless, there is limited efficacy of these drugs against hookworm infection and, to a greater extent, against trichuriasis. We describe a protocol for a trial investigating the efficacy and safety of the co-administration of ivermectin and albendazole against trichuriasis.

Methods: A double-blind, placebo-controlled randomized controlled trial will be conducted in three countries (Côte d'Ivoire, Tanzania and Lao PDR) with the aim to determine the efficacy, safety and extended effects of co-administered ivermectin and albendazole compared to standard albendazole monotherapy. We will enroll 600 participants aged 6-60 years in each setting. The primary outcome is cure rate (CR) against Trichuris trichiura infection as assessed by Kato-Katz 14-21 days after treatment. Secondary outcomes include CRs against concomitant soil-transmitted helminth (STH) infections (Ascaris lumbricoides, hookworm and Strongyloides stercoralis) and egg reduction rates (ERRs) against STH at 14-21 days, 180 days and 360 days. Tolerability of treatment, infection status assessed by polymerase chain reaction (PCR), and potential benefits of deworming on nutritional and morbidity indicators will be assessed. The primary analysis will include an available-case set and use logistic regression models adjusted for age, sex and weight.

Discussion: This trial will provide robust results on the efficacy and safety of co-administration of ivermectin and albendazole with the aim to better inform WHO recommendations on control of STHs. Furthermore, secondary and explanatory outcomes will provide direct evidence on the extended effects of combination therapy and insight on the relationship between nutrition and morbidity parameters and infection status and intensity.

Trial registration: NCT03527732 (date assigned: 17 May 2018).

Keywords: Albendazole; Côte d’Ivoire; Drug efficacy; Drug safety; Ivermectin; Lao PDR; Soil-transmitted helminthiasis; Tanzania; Trichuris trichiura.

Conflict of interest statement

Ethics approval and consent to participate

This study protocol has been approved by the institutional research commissions of the Centre Suisse des Recherches Scientifiques (CSRS) in Abidjan, Public Health Laboratory Ivo de Carneri (PHL-IdC) in Pemba, National Institute of Public Health (NIOPH) in Vientiane, and Swiss TPH in Basel. Ethical approval was obtained from the ethics committees in Switzerland: “Ethikkommission Nordwest- und Zentralschweiz” (BASEC Nr Req-2018-00494; date of approval 05 July 2018); in Côte d’Ivoire: Comité National d’Éthique et de la Recherche, Ministère de la Santé et de Lutte contre le SIDA (reference no. 088–18/MSHP/CNESVS-km; date of approval 24 January 2019) and Direction de la Pharmacie, du Médicament et des Laboratoires (reference no. ECCI00918; date of approval to be issued); in Pemba: Zanzibar Medical Research and Ethics Committee, Ministry of Health (protocol no. ZAMREC/0003/Feb/2018; date of approval 23 May 2018); and in Lao PDR: National Ethics Committee for Health Research, Ministry of Health (reference no. 093/NECHR; date of approval 23 October 2018). Written informed consent will be sought from adults and parents or legal guardians of children below the age of adulthood (21 years in Côte d’Ivoire and 18 years in Pemba and Lao PDR) prior to study enrollment. Children aged below the age of adulthood will sign an informed assent form. The informed consent is provided by trained field staff in the local language and the participant will receive a copy of the consent form in written format. Participation is voluntary and study participants have the right to withdraw from the study at any given point in time with no further obligations. Participants will be treated free of charge at the end of the trial with albendazole. A general liability insurance of the Swiss TPH is in place (Winterthur Police Nr. 4,746,321) and patient liability insurances will be issued in the respective trial countries to cover any potential study-related harm.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

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Figures

Fig. 1
Fig. 1
Design and timeline of the randomized controlled trial to be implemented in each of three settings. The study is designed as a two-armed trial including one arm with a single drug administration (arm A; albendazole) and one arm with combined treatment through co-administration of separate tablets (arm B; ivermectin and albendazole). The trial will be conducted as a multi-country study with two settings in Africa and one in Asia, namely Côte d’Ivoire, Pemba (Zanzibar, Tanzania) and Lao PDR

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