Efficacy and Safety of IVM/ALB Co-administration

NCT03527732 | Completed Phase 2 Results

• 1 other identifier: 1
• Study Type: interventional
• Target: 1,673
• Locations: 3 countries
• Sites: 3

Brief Summary

This study is a double-blind randomized clinical trial conducted with two settings in Africa and one in Asia, namely Côte d'Ivoire, Pemba (Zanzibar, Tanzania) and Lao PDR. This study aims at providing evidence on the efficacy and safety of co-administered albendazole and ivermectin versus albendazole monotherapy (standard of care) against whipworm (T. trichiura) infections in children and adults (6-60 years). The efficacy of the treatment and potential extended effects on follow-up prevalence will be determined 14-21 days, 6 months and 12 months post-treatment by collecting another two stool samples. The cure rate will be calculated as the percentage of egg-positive subjects at baseline who become egg-negative after treatment.

Conditions

Trichuriasis

Outcome Measures

Primary Outcomes (1)

• Number of Participants T. Trichiura Egg Negative Post-Treatment (Cured)

  The conversion from being egg positive pre-treatment to egg negative post-treatment, or cure rate (CR).

  14-21 days after treatment

Secondary Outcomes (4)

• Number of Participants T. Trichiura Egg Negative Post-Treatment (Cured) After 6 and 12 Months Post Treatment

  6 and 12 months after treatment

• Egg-reduction Rate (ERR) Against T. Trichiura

  14-21 days, 6 months and 12 months after treatment

• Number of Participants With Concomitant Soil-transmitted Helminth Infections Egg Negative Post-Treatment (Cured)

  14-21 days, 6 months and 12 months after treatment

• Egg-reduction Rates (ERRs) Against Concomitant Soil-transmitted Helminth Infections.

  14-21 days, 6 months and 12 months after treatment

Study Arms (2)

Arm A: albendazole

PLACEBO COMPARATOR

400 mg albendazole single tablet (Zentel®) and 200µg/kg using 3mg tablets of placebo at day 0 administered orally

Drug: Albendazole

Arm B: albendazole and ivermectin

EXPERIMENTAL

400 mg albendazole single tablet (Zentel®) and 200µg/kg using 3mg tablets of ivermectin (Stromectol®) at day 0 administered orally

Drug: Albendazole and Ivermectin

Interventions

Albendazole DRUG

Monotherapy of albendazole (400 mg)

Also known as: Zentel®

Arm A: albendazole

Albendazole and Ivermectin DRUG

Combination therapy of albendazole (400 mg) and ivermectin (200 µg/kg)

Also known as: Zentel® and Stromectol®

Arm B: albendazole and ivermectin

Eligibility Criteria

• Age: 6 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Written informed consent signed by either the participant him/herself (≥21 years of age) or by parents and/or caregivers for children/adolescents; and written assent by child/adolescent (aged 6-20 years).
• Agree to comply with study procedures, including provision of two stool samples at the beginning (baseline) and on three follow-up assessments (approximately 3 weeks, 6 months, and 12 months later).
• Aged ≥6 to \<= 60 years for parallel group trial and ≥6 to \<=12 years for DF study.
• At least two slides of the quadruple Kato-Katz thick smears positive for T. trichiura and infection intensities of at least 100 EPG.

You may not qualify if:

• No written informed consent by individual/parents and/or caregiver.
• Presence of major systemic illnesses, e.g. severe anemia (below 80 g/l Hb according to WHO \[28\]), clinical malaria as assessed by a medical doctor (positive Plasmodium RDT and ≥38 °C ear temperature), upon initial clinical assessment.
• History of acute or severe chronic disease (e.g. cancer, diabetes, chronic heart, liver or renal disease).
• Recent use of anthelmintic drug (within past 4 weeks).
• Attending other clinical trials during the study.
• Negative or low egg count (less than 100 EPG or less than 2 out of 4 slides positive) diagnostic result for T. trichiura eggs in the stool.
• Known allergy to study medications (i.e. albendazole and ivermectin).
• Pregnancy or lactating in the 1st week after birth (according to WHO guidelines within LF control programs \[29\]).
• Currently taking medication with known interaction (e.g. for albendazole: cimetidine, praziquantel and dexamethasone; for ivermectin: warfarin).

Sponsors & Collaborators

• Jennifer Keiser: lead
• Centre Suisse de Recherches Scientifiques en Cote d'Ivoire: collaborator
• Lao Tropical and Public Health Institute: collaborator
• Public Health Laboratory of Pemba, Tanzania: collaborator

Study Sites (3)

Centre Suisse de Recherches Scientifiques en Côte d'Ivoire (CSRS)

Abidjan, Côte d’Ivoire

Location

Lao Tropical and Public Health Institute

Vientiane, Laos

Location

Public Health Laboratory Ivo de Carneri, P.O. Box 122

Chake Chake, Pemba, Tanzania

Location

Related Publications (5)

• Welsche S, Schneeberger PHH, Hattendorf J, Sayasone S, Hurlimann E, Keiser J. Egg excretion patterns of soil-transmitted helminth infections in humans following albendazole-ivermectin and albendazole treatment. PLoS Negl Trop Dis. 2024 Mar 22;18(3):e0012073. doi: 10.1371/journal.pntd.0012073. eCollection 2024 Mar.

  PMID: 38517907 DERIVED

• Schneeberger PHH, Gueuning M, Welsche S, Hurlimann E, Dommann J, Haberli C, Frey JE, Sayasone S, Keiser J. Different gut microbial communities correlate with efficacy of albendazole-ivermectin against soil-transmitted helminthiases. Nat Commun. 2022 Feb 25;13(1):1063. doi: 10.1038/s41467-022-28658-1.

  PMID: 35217670 DERIVED

• Hurlimann E, Keller L, Patel C, Welsche S, Hattendorf J, Ali SM, Ame SM, Sayasone S, Coulibaly JT, Keiser J. Efficacy and safety of co-administered ivermectin and albendazole in school-aged children and adults infected with Trichuris trichiura in Cote d'Ivoire, Laos, and Pemba Island, Tanzania: a double-blind, parallel-group, phase 3, randomised controlled trial. Lancet Infect Dis. 2022 Jan;22(1):123-135. doi: 10.1016/S1473-3099(21)00421-7. Epub 2021 Nov 29.

  PMID: 34856181 DERIVED

• Keller L, Welsche S, Patel C, Sayasone S, Ali SM, Ame SM, Hattendorf J, Hurlimann E, Keiser J. Long-term outcomes of ivermectin-albendazole versus albendazole alone against soil-transmitted helminths: Results from randomized controlled trials in Lao PDR and Pemba Island, Tanzania. PLoS Negl Trop Dis. 2021 Jun 30;15(6):e0009561. doi: 10.1371/journal.pntd.0009561. eCollection 2021 Jun.

  PMID: 34191812 DERIVED

• Patel C, Hurlimann E, Keller L, Hattendorf J, Sayasone S, Ali SM, Ame SM, Coulibaly JT, Keiser J. 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. BMC Infect Dis. 2019 Mar 18;19(1):262. doi: 10.1186/s12879-019-3882-x.

  PMID: 30885157 DERIVED

MeSH Terms

Conditions

Trichuriasis

Interventions

Albendazole; Ivermectin

Condition Hierarchy (Ancestors)

Enoplida Infections; Adenophorea Infections; Nematode Infections; Helminthiasis; Parasitic Diseases; Infections

Intervention Hierarchy (Ancestors)

Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Macrolides; Polyketides; Lactones

Results Point of Contact

• Title: Prof. Dr. Jennifer Keiser
• Organization: Swiss Tropical and Public Health Institute

jennifer.keiser@swisstph.ch

+41 (61) 284 8218

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The parallel group trial will be double blinded (i.e. study participants and the trial team/researchers conducting the treatment and assessing the outcomes will be blinded) using repacked tablets including appearance-matched placebos while the dose-finding study will be single blinded (i.e. all outcome assessors except the investigators who provide the treatment and the study participants who get either active or placebo tablets matching in appearance will be blinded) due to the nature of this study (i.e. including ascending doses).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Jennifer Keiser, PhD

Study Record Dates

• First Submitted: May 3, 2018
• First Posted: May 17, 2018
• Study Start: September 9, 2018
• Primary Completion: May 15, 2020
• Study Completion: July 15, 2020
• Last Updated: March 20, 2024
• Results First Posted: March 20, 2024

Record last verified: 2023-08

Locations

CÔ (1); TA (1); LA (1)