Lymphatic Filariasis
Conditions
Keywords
Lymphatic filariasis, microfilaria, Albendazole, ivermectin, human immunodeficiency
Brief summary
Albendazole and ivermectin are currently used in combination for annual mass treatment of lymphatic filariasis in Africa. Although the drugs have been donated, the cost of such programmes is very high and has proven to be a major impediment to the success of programmes in many countries with limited financial resources. Data from albendazole treatment of other filarial infections and one study comparing single to multi-dose Diethycarbamazine/albendazole in lymphatic filariasis suggest that increased dose and/or frequency of albendazole dosing may be more effective in clearing microfilariae. It is essential to determine whether such higher doses are indeed beneficial since this could have far-reaching effects on the conduct and management of the main mass treatment programmes and also in the management of programmes as they near elimination.
Detailed description
The proposed study will enrol up to 120 volunteers with microfilaremic Wuchereria bancrofti infection who would be randomized to receive standard annual treatment (albendazole 400 mg + ivermectin 200 mcg/kg), annual treatment with an increased dose of albendazole (albendazole 800 mg + ivermectin 200400 mcg/kg) or semi-annual treatment with a standard (albendazole 400 mg + ivermectin 200 mcg/kg), or an increased albendazole dose (albendazole 800 mg + ivermectin 200 400 mcg/kg). Microfilarial levels, as well as measures of adult worm burden (circulating antigen) will be followed every six months for two years to determine whether the higher doses, or more frequent regimens are more effective. The data obtained would be used, in combination with the data from other similar studies being conducted in Mali and in India to advise the Global Programme for the Elimination of Lymphatic Filariasis (GPELF) on improved methods of treatment both for mass treatment and for the management of problem areas within the global programme.
Interventions
DRUGAlbendazole 400mg and ivermectin 200mcg/kg
400 mg orally given annually
albendazole 800 mg and ivermectin 400mg orally given annually
DRUGalbendazole 800mg and ivermectin 400mcg/kg bi-annually
albendazole 800mg and ivermectin 400mcg/kg given twice a year
Sponsors
Emory University
London School of Hygiene and Tropical Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* understand and sign informed consent * willing to undergo night blood sampling every 6 months for 2 years * Age 18 to 55 years * Haemoglobin of equal or above 9g/dl * Microfilarial level of equal or above 80mg/dl
Exclusion criteria
* Non- consenting * Pregnancy or lactation * Treatment with albendazole or ivermectin within the previous 6 months * Known allergy to the study drugs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving Microfilarial Clearance | 12 months | Microfilaria clearance will be assessed in regard to dosage as well as frequency of treatment. Microfilarial clearance is defined by non-detection of microfilaria in the night blood sample. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Microfilarial Clearance at 24 Months of Follow up | 24 months | Microfilaria will be detected using the nucleopore filtration technique and analysed according to the respective treatment arms at the 24 month time point. Microfilarial clearance will be defined by non-detection of microfilaria in the night blood sample |
Countries
Malawi
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Albendazole 400mg and Ivermectin 200mcg/kg Annual Albendazole 400mg and ivermectin 200mcg/kg: 400 mg orally given once a year | 18 |
| Albendazole 800mg and Ivermectin 400mcg/kg Annual Albendazole and ivermectin: albendazole 800 mg and ivermectin 400mg orally given once a year | 17 |
| Albendazole 400mg and Ivermectin 200mcg/kg Biannual Albendazole 400mg and ivermectin 200mcg/kg given twice a year | 18 |
| Albendazole 800mg and Ivermectin 400mcg/kg Bi-annual Albendazole 800mg and ivermectin 400mcg/kg given twice a year | 17 |
| Total | 70 |
Baseline characteristics
| Characteristic | Albendazole 400mg and Ivermectin 200mcg/kg Annual | Albendazole 800mg and Ivermectin 400mcg/kg Annual | Albendazole 400mg and Ivermectin 200mcg/kg Biannual | Albendazole 800mg and Ivermectin 400mcg/kg Bi-annual | Total |
|---|---|---|---|---|---|
| Age, Continuous | 32.5 years | 31 years | 27.5 years | 35 years | 33 years |
| Eosinophil count | 1300 cells/uL | 1400 cells/uL | 1600 cells/uL | 1100 cells/uL | 1300 cells/uL |
| HIV status | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Microfilarial count /uL | 464.7 microfilaria/uL | 338.7 microfilaria/uL | 204.5 microfilaria/uL | 264.7 microfilaria/uL | 298.6 microfilaria/uL |
| Region of Enrollment Malawi | 18 participants | 17 participants | 18 participants | 17 participants | 70 participants |
| Sex: Female, Male Female | 3 Participants | 6 Participants | 7 Participants | 7 Participants | 23 Participants |
| Sex: Female, Male Male | 15 Participants | 11 Participants | 11 Participants | 10 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 18 | 7 / 17 | 6 / 18 | 4 / 17 |
| serious Total, serious adverse events | 0 / 18 | 0 / 17 | 0 / 18 | 0 / 17 |
Outcome results
Primary
Number of Participants Achieving Microfilarial Clearance
Microfilaria clearance will be assessed in regard to dosage as well as frequency of treatment. Microfilarial clearance is defined by non-detection of microfilaria in the night blood sample.
Time frame: 12 months
Population: Number of participants with non detectable microfilaria at follow up
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Albendazole 400mg and Ivermectin 200mcg/kg Annually | Number of Participants Achieving Microfilarial Clearance | 15 participants |
| Albendazole 800mg and Ivermectin 400mcg/kg Annually | Number of Participants Achieving Microfilarial Clearance | 14 participants |
| Albendazole 400mg and Ivermectin 200mcg/kg Biannually | Number of Participants Achieving Microfilarial Clearance | 13 participants |
| Albendazole 800mg and Ivermectin 400mcg /kg Bi-annually | Number of Participants Achieving Microfilarial Clearance | 17 participants |
Secondary
Number of Participants With Microfilarial Clearance at 24 Months of Follow up
Microfilaria will be detected using the nucleopore filtration technique and analysed according to the respective treatment arms at the 24 month time point. Microfilarial clearance will be defined by non-detection of microfilaria in the night blood sample
Time frame: 24 months
Population: Intention to treat, with last result carried forward in the case of missing visit
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Albendazole 400mg and Ivermectin 200mcg/kg Annually | Number of Participants With Microfilarial Clearance at 24 Months of Follow up | 17 participants |
| Albendazole 800mg and Ivermectin 400mcg/kg Annually | Number of Participants With Microfilarial Clearance at 24 Months of Follow up | 17 participants |
| Albendazole 400mg and Ivermectin 200mcg/kg Biannually | Number of Participants With Microfilarial Clearance at 24 Months of Follow up | 14 participants |
| Albendazole 800mg and Ivermectin 400mcg /kg Bi-annually | Number of Participants With Microfilarial Clearance at 24 Months of Follow up | 17 participants |