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

• Sponsor: London School of Hygiene and Tropical Medicine (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01213576
• Collaborator: Emory University (Other)
• Enrollment: 70
• Location: 1
• Arms: 4
• Duration (Months): 37
• Patients Per Site Per Month: 1.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphatic Filariasis	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	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Efficacy of Higher Albendazole and Ivermectin Doses on Wuchereria Bancrofti Microfilarial Clearance in Malawi, Open Label Study
• Study Start Date: Jan 1, 2009
• Actual Primary Completion Date: Feb 1, 2012
• Actual Study Completion Date: Feb 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: albendazole 400mg and ivermectin 200mcg/kg Annual treatment	Drug: Albendazole 400mg and ivermectin 200mcg/kg; 400 mg orally given annually; Drug: Albendazole 400mg and ivermectin 200mcg/kg; Albendazole 400mg and ivermectin 200mcg/kg given twice a year
Active Comparator: Albendazole 800mg and ivermectin 400mcg/kg Annual treatment	Drug: Albendazole and ivermectin; albendazole 800 mg and ivermectin 400mg orally given annually
Active Comparator: Albendazole 400mg and ivermectin 200mcg/kg albendazole 400mg and ivermectin 200mcg/kg given twice a year	Drug: Albendazole 400mg and ivermectin 200mcg/kg; 400 mg orally given annually; Drug: Albendazole 400mg and ivermectin 200mcg/kg; Albendazole 400mg and ivermectin 200mcg/kg given twice a year
Active Comparator: Albendazole 800mg and ivermectin 400mcg /kg bi-annually Albendazole 800mg and ivermectin 400mcg/kg given twice a year	Drug: albendazole 800mg and ivermectin 400mcg/kg bi-annually; albendazole 800mg and ivermectin 400mcg/kg given twice a year

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Karonga Prevention Study	Karonga		Malawi

Sponsors and Collaborators

• London School of Hygiene and Tropical Medicine
• Emory University

Investigators

• Principal Investigator: Neil French, MB ChB PHD, London School of Hygiene and Tropical Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Neil French, Reader In Infectious Disease Epidemiology/Director KPS, London School of Hygiene and Tropical Medicine
• ClinicalTrials.gov Identifier: NCT01213576
• Other Study ID Numbers: FED-311207
• First Posted: Oct 4, 2010
• Last Update Posted: Feb 27, 2015
• Last Verified: Feb 1, 2015

• Keywords provided by Neil French, Reader In Infectious Disease Epidemiology/Director KPS, London School of Hygiene and Tropical Medicine: Lymphatic filariasis; microfilaria; Albendazole; ivermectin; human immunodeficiency
• Additional relevant MeSH terms: Filariasis; Elephantiasis, Filarial; Elephantiasis; Ivermectin; Albendazole

Study Results

Participant Flow

Arm/Group Title	Albendazole 400mg and Ivermectin 200mcg/kg Annually	Albendazole 800mg and Ivermectin 400mcg/kg Annually	Albendazole 400mg and Ivermectin 200mcg/kg Biannually	Albendazole 800mg and Ivermectin 400mcg /kg Bi-annually
Arm/Group Description	Once a year treatment Albendazole 400mg and ivermectin 200mcg/kg: 400 mg oral	Once a year treatment Albendazole and ivermectin: albendazole 800 mg and ivermectin 400mg oral	Twice a year albendazole 400mg and ivermectin 200mcg/kg given twice a year	Twice a year Albendazole 800mg and ivermectin 400mcg/kg given twice a year
Period Title: Overall Study
STARTED	18	17	18	17
COMPLETED	15	13	13	13
NOT COMPLETED	3	4	5	4

Baseline Characteristics

Arm/Group Title	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
Arm/Group Description	Albendazole 400mg and ivermectin 200mcg/kg: 400 mg orally given once a year	Albendazole and ivermectin: albendazole 800 mg and ivermectin 400mg orally given once a year	Albendazole 400mg and ivermectin 200mcg/kg given twice a year	Albendazole 800mg and ivermectin 400mcg/kg given twice a year	Total of all reporting groups
Overall Participants	18	17	18	17	70
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	32.5	31	27.5	35	33
Sex: Female, Male (Count of Participants)
Female	3 16.7%	6 35.3%	7 38.9%	7 41.2%	23 32.9%
Male	15 83.3%	11 64.7%	11 61.1%	10 58.8%	47 67.1%
Region of Enrollment (participants) [Number]
Malawi	18 100%	17 100%	18 100%	17 100%	70 100%
Microfilarial count /uL (microfilaria/uL) [Geometric Mean (Full Range) ]
Geometric Mean (Full Range) [microfilaria/uL]	464.7	338.7	204.5	264.7	298.6
HIV status (participants) [Number]
Number [participants]	0 0%	0 0%	0 0%	0 0%	0 0%
Eosinophil count (cells/uL) [Geometric Mean (Full Range) ]
Geometric Mean (Full Range) [cells/uL]	1300	1400	1600	1100	1300

Outcome Measures

1. Primary Outcome

Title	Number of Participants Achieving Microfilarial Clearance
Description	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

Outcome Measure Data

Analysis Population Description

Number of participants with non detectable microfilaria at follow up

Arm/Group Title	Albendazole 400mg and Ivermectin 200mcg/kg Annually	Albendazole 800mg and Ivermectin 400mcg/kg Annually	Albendazole 400mg and Ivermectin 200mcg/kg Biannually	Albendazole 800mg and Ivermectin 400mcg /kg Bi-annually
Arm/Group Description	Once a year treatment Albendazole 400mg and ivermectin 200mcg/kg: 400 mg oral	Once a year treatment Albendazole and ivermectin: albendazole 800 mg and ivermectin 400mg oral	Twice a year albendazole 400mg and ivermectin 200mcg/kg given twice a year	Twice a year Albendazole 800mg and ivermectin 400mcg/kg given twice a year
Measure Participants	18	17	18	17
Number [participants]	15 83.3%	14 82.4%	13 72.2%	17 100%

2. Secondary Outcome

Title	Number of Participants With Microfilarial Clearance at 24 Months of Follow up
Description	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

Outcome Measure Data

Analysis Population Description

Intention to treat, with last result carried forward in the case of missing visit

Arm/Group Title	Albendazole 400mg and Ivermectin 200mcg/kg Annually	Albendazole 800mg and Ivermectin 400mcg/kg Annually	Albendazole 400mg and Ivermectin 200mcg/kg Biannually	Albendazole 800mg and Ivermectin 400mcg /kg Bi-annually
Arm/Group Description	Once a year treatment Albendazole 400mg and ivermectin 200mcg/kg: 400 mg oral	Once a year treatment Albendazole and ivermectin: albendazole 800 mg and ivermectin 400mg oral	Twice a year albendazole 400mg and ivermectin 200mcg/kg given twice a year	Twice a year Albendazole 800mg and ivermectin 400mcg/kg given twice a year
Measure Participants	18	17	18	17
Number [participants]	17 94.4%	17 100%	14 77.8%	17 100%

Adverse Events

Arm/Group Title	Albendazole 400mg and Ivermectin 200mcg/kg Annually		Albendazole 800mg and Ivermectin 400mcg/kg Annually		Albendazole 400mg and Ivermectin 200mcg/kg Biannually		Albendazole 800mg and Ivermectin 400mcg /kg Bi-annually
Arm/Group Description	Once a year treatment Albendazole 400mg and ivermectin 200mcg/kg: 400 mg oral		Once a year treatment Albendazole and ivermectin: albendazole 800 mg and ivermectin 400mg oral		Twice a year albendazole 400mg and ivermectin 200mcg/kg given twice a year		Twice a year Albendazole 800mg and ivermectin 400mcg/kg given twice a year
All Cause Mortality
	Albendazole 400mg and Ivermectin 200mcg/kg Annually		Albendazole 800mg and Ivermectin 400mcg/kg Annually		Albendazole 400mg and Ivermectin 200mcg/kg Biannually		Albendazole 800mg and Ivermectin 400mcg /kg Bi-annually
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Albendazole 400mg and Ivermectin 200mcg/kg Annually		Albendazole 800mg and Ivermectin 400mcg/kg Annually		Albendazole 400mg and Ivermectin 200mcg/kg Biannually		Albendazole 800mg and Ivermectin 400mcg /kg Bi-annually
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/17 (0%)		0/18 (0%)		0/17 (0%)
Other (Not Including Serious) Adverse Events
	Albendazole 400mg and Ivermectin 200mcg/kg Annually		Albendazole 800mg and Ivermectin 400mcg/kg Annually		Albendazole 400mg and Ivermectin 200mcg/kg Biannually		Albendazole 800mg and Ivermectin 400mcg /kg Bi-annually
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/18 (27.8%)		7/17 (41.2%)		6/18 (33.3%)		4/17 (23.5%)
General disorders
Fever	2/18 (11.1%)		4/17 (23.5%)		3/18 (16.7%)		1/17 (5.9%)
headache	3/18 (16.7%)		4/17 (23.5%)		4/18 (22.2%)		2/17 (11.8%)
joint pains	2/18 (11.1%)		1/17 (5.9%)		3/18 (16.7%)		2/17 (11.8%)
abdominal pains	1/18 (5.6%)		2/17 (11.8%)		1/18 (5.6%)		1/17 (5.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.