Safety of Co-administration of IDA and Azithromycin for NTDs ( ComboNTDs )

Lihir Medical Centre

Status and phase: Completed; Phase 3

Conditions: Lymphatic Filariases; Strongyloidiasis; Yaws; Scabies; Trachoma

Treatments: Drug: Diethylcarbamazine on day 1; Drug: Azithromycin on Day 8; Drug: Albendazole on Day 1; Drug: Ivermectin on Day 1; Drug: Azithromycin on Day 1

Study type: Interventional

Funder types: Other

Identifiers

NCT03676140

ComboNTDs - CRT

Details and patient eligibility

About

This is a cluster randomised trial evaluating the safety of co-administering Azithromycin alongside the new IDA (Ivermectin, Diethylcarbamazine, Albendazole) combination treatment for LF.

Treatment will be provided as a single dose Mass Drug Administration (MDA) to the whole community. Communities will be randomised to receive either treatment with IDA and Azithromycin on the same day or separately.

Active monitoring for adverse events will be conducted and the frequency of adverse events compared between individuals receiving combined MDA or separate MDA.

Full description

Recent studies have shown that single-dose combination therapy with three antifilarial drugs (Ivermectin [IVE] + DEC + ALB) called IDA is superior to current regimens used in LF elimination and may help accelerate LF elimination. WHO guidelines have changed to recommend IDA in countries endemic for LF outside sub-Saharan Africa like Papua New Guinea.

Additional benefits of IVE are its activity against scabies and Strongyloides. Treatment with IVE has shown to reduce the high prevalence of scabies in a village and in randomized control trials elsewhere in the Pacific. Of particular importance was the finding that IVE was highly effective against Strongyloides with a >95% reduction in prevalence sustained for nine months.

Increasingly, the desirability of linking LF programs with other public health initiatives also based on MDA is being appreciated. The existing programmatic infrastructure developed for LF campaign presents an attractive vehicle for a demonstration project of integration of MDAs against multiple Neglected Tropical Diseases (NTDs). The macrolide antibiotic azithromycin (AZI) has been demonstrated to be highly effective as MDA for yaws control and AZI is a highly effective and well-tolerated antibiotic treatment for trachoma that is able to clear ocular infection with a single oral dose and is well tolerated.

Currently LF/STH/Scabies/strongyloides and yaws/trachoma are treated separately. Integration of these existing MDA programs has the potential to be highly cost-effective as a population health intervention. Integration includes both the safe co-administration of medicines and operational planning, and it is currently advocated by WHO.

Enrollment: 20,000 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion criteria

• Able to give consent

Exclusion criteria

• Unable to give consent.
• Less than 5 years of age (not eligible for ivermectin)**
• Pregnant women (azithromycin only, not eligible for albendazole and ivermectin)
• Lactating women (Only administered azithromycin and albendazole, not eligible for ivermectin)**
• History of allergies to the drugs being studied
• Residents who cannot swallow tablets

Note that patients that are not eligible for a specific drug will receive all other treatments and will be followed up through the same procedure as the other participants drug therapy to try to track any AEs attributed to specific drug combinations

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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20,000 participants in 2 patient groups

Separate Administration

Active Comparator group

Description:

'Albendazole on day 1' 'Ivermectin on day 1' 'Diethylcarbamazine on day 1' 'Azithromycin on day 8'

Treatment:

Drug: Ivermectin on Day 1

Drug: Azithromycin on Day 8

Drug: Albendazole on Day 1

Drug: Diethylcarbamazine on day 1

Co-Administration

Experimental group

Description:

'Albendazole on day 1' 'Ivermectin on day 1' 'Diethylcarbamazine on day 1' 'Azithromycin on day 1'

Treatment:

Drug: Azithromycin on Day 1

Drug: Ivermectin on Day 1

Drug: Albendazole on Day 1

Drug: Diethylcarbamazine on day 1