Efficacy of Higher Albendazole and Ivermectin Doses on Wuchereria Bancrofti Microfilarial Clearance in Malawi

Study Overview
=================
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.

Official Title
-----------------
Efficacy of Higher Albendazole and Ivermectin Doses on Wuchereria Bancrofti Microfilarial Clearance in Malawi, Open Label Study

Conditions
-----------------
Lymphatic Filariasis

Intervention / Treatment
-----------------
* Drug: Albendazole 400mg and ivermectin 200mcg/kg
* Drug: Albendazole and ivermectin
* Drug: Albendazole 400mg and ivermectin 200mcg/kg
* Drug: albendazole 800mg and ivermectin 400mcg/kg bi-annually


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: albendazole 400mg and ivermectin 200mcg/kg<br>Annual treatment | Drug: Albendazole 400mg and ivermectin 200mcg/kg<br>* 400 mg orally given annually<br>Drug: Albendazole 400mg and ivermectin 200mcg/kg<br>* Albendazole 400mg and ivermectin 200mcg/kg given twice a year<br>|
| Active Comparator: Albendazole 800mg and ivermectin 400mcg/kg<br>Annual treatment | Drug: Albendazole and ivermectin<br>* albendazole 800 mg and ivermectin 400mg orally given annually<br>|
| Active Comparator: Albendazole 400mg and ivermectin 200mcg/kg<br>albendazole 400mg and ivermectin 200mcg/kg given twice a year | Drug: Albendazole 400mg and ivermectin 200mcg/kg<br>* 400 mg orally given annually<br>Drug: Albendazole 400mg and ivermectin 200mcg/kg<br>* Albendazole 400mg and ivermectin 200mcg/kg given twice a year<br>|
| Active Comparator: Albendazole 800mg and ivermectin 400mcg /kg bi-annually<br>Albendazole 800mg and ivermectin 400mcg/kg given twice a year | Drug: albendazole 800mg and ivermectin 400mcg/kg bi-annually<br>* albendazole 800mg and ivermectin 400mcg/kg given twice a year<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Lymphatic filariasis, microfilaria, Albendazole, ivermectin, human immunodeficiency