Effect of Albendazole Dose on Treatment of Lymphatic Filariasis

• ClinicalTrials.gov Identifier: NCT00511004
• Recruitment Status: Completed
• First Posted: August 3, 2007
• Results First Posted: August 31, 2015
• Last Update Posted: August 31, 2015
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Lymphatic Filariasis
• Interventions: Drug: Albendazole; Drug: Diethylcarbamazine
• Enrollment: 40

Participant Flow

Recruitment Details	Adults living in Kerala, India with Brugia malayi microfilaremia were recruited from field sites around the city of Alleppey and the study performed in the outpatient department of the TD Medical College.
Pre-assignment Details

Arm/Group Title	Standard Therapy Annual DEC/ALB	High Dose Annual DEC/ALB	High Dose Semiannual DEC/ALB
Arm/Group Description	Group randomized to standard therapy that consists of Annual diethylcarbamazine (300 mg) and albendazole (400mg)	Group randomized to yearly high dose albendazole that consists of Annual diethylcarbamazine (300 mg) and albendazole (800mg)	Group randomized to twice-yearly high dose albendazole that consists of Annual diethylcarbamazine (300 mg) and albendazole (800mg)
Period Title: Overall Study
Started	13	13	14
Completed	13	13	10
Not Completed	0	0	4
Reason Not Completed
Lost to Follow-up	0	0	4

Baseline Characteristics

Arm/Group Title		Standard Therapy Annual DEC/ALB	High Dose Annual DEC/ALB	High Dose Semiannual DEC/ALB	Total
Arm/Group Description		Group randomized to standard therapy that consists of Annual diethylcarbamazine (300 mg) and albendazole (400mg)	Group randomized to yearly high dose albendazole that consists of Annual diethylcarbamazine (300 mg) and albendazole (800mg)	Group randomized to twice-yearly high dose albendazole that consists of Annual diethylcarbamazine (300 mg) and albendazole (800mg)	Total of all reporting groups
Overall Number of Baseline Participants		13	13	14	40
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	13 participants	13 participants	14 participants	40 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	13 100.0%	13 100.0%	14 100.0%	40 100.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	13 participants	13 participants	14 participants	40 participants
		36; (18 to 50)	39; (18 to 50)	37; (19 to 54)	37; (18 to 54)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	13 participants	13 participants	14 participants	40 participants
	Female	9 69.2%	10 76.9%	10 71.4%	29 72.5%
	Male	4 30.8%	3 23.1%	4 28.6%	11 27.5%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
India	Number Analyzed	13 participants	13 participants	14 participants	40 participants
		13	13	14	40
Blood microfilaremia (mf/ml); Median (Full Range); Unit of measure: MF/ML
	Number Analyzed	13 participants	13 participants	14 participants	40 participants
		412; (64 to 912)	264; (112 to 1244)	384; (108 to 748)	384; (64 to 1244)

Outcome Measures

1. Primary Outcome

Title	Microfilarial Counts at 1 Year
Description	Night time microfilarial counts at 1 year
Time Frame	1 year from time enrolled

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard Therapy Annual DEC/ALB	High Dose Annual DEC/ALB	High Dose Semiannual DEC/ALB
Arm/Group Description:	Group randomized to standard therapy that consists of Annual diethylcarbamazine (300 mg) and albendazole (400mg)	Group randomized to yearly high dose albendazole that consists of Annual diethylcarbamazine (300 mg) and albendazole (800mg)	Group randomized to twice-yearly high dose albendazole that consists of Annual diethylcarbamazine (300 mg) and albendazole (800mg)
Overall Number of Participants Analyzed	13	13	13
Median (Full Range); Unit of Measure: MF/ML
	0; (0 to 20)	0; (0 to 12)	0; (0 to 9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Therapy Annual DEC/ALB, High Dose Annual DEC/ALB, High Dose Semiannual DEC/ALB
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.2
	Comments	Adjusted for multiple comparisons
	Method	Fisher Exact
	Comments	[Not Specified]

2. Secondary Outcome

Title	Adult Worm Burdens at 2 Years
Description	Doppler detected worm nests at 2 years
Time Frame	2 years from the time enrolled.

Outcome Measure Data

Analysis Population Description

By 2 years, 4 subjects in High Dose Group lost to followup

Arm/Group Title	Standard Therapy Annual DEC/ALB	High Dose Annual DEC/ALB	High Dose Semiannual DEC/ALB
Arm/Group Description:	Group randomized to standard therapy that consists of Annual diethylcarbamazine (300 mg) and albendazole (400mg)	Group randomized to yearly high dose albendazole that consists of Annual diethylcarbamazine (300 mg) and albendazole (800mg)	Group randomized to twice-yearly high dose albendazole that consists of Annual diethylcarbamazine (300 mg) and albendazole (800mg)
Overall Number of Participants Analyzed	13	13	10
Median (Full Range); Unit of Measure: Number of nests
	0; (0 to 0)	0; (0 to 0)	0; (0 to 0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Therapy Annual DEC/ALB, High Dose Annual DEC/ALB, High Dose Semiannual DEC/ALB
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

3. Secondary Outcome

Title	Microfilarial Levels at 2 Years
Description	Night time microfilarial levels at 2 years
Time Frame	2 years from time enrolled

Outcome Measure Data

Analysis Population Description

By 2 years, 4 subjects in High Dose Group lost to followup

Arm/Group Title	Diethylcarbamazine/Albendazole -STD	Diethylcarbamazine/Albendazole- HD1	Diethylcarbamazine/Albendazole-HD2
Arm/Group Description:	Standard therapy of diethylcarbamazine (DEC) (300mg) and albendazole (400mg) yearly Albendazole: Comparing 400 mg to 800 mg dose Diethylcarbamazine: Providing diethylcarbamazine more frequently in combination with albendazole	High dose of DEC (300mg) and albendazole (800mg) yearly Albendazole: Comparing 400 mg to 800 mg dose Diethylcarbamazine: Providing diethylcarbamazine more frequently in combination with albendazole	High dose of DEC (300mg) and albendazole (800mg) twice yearly (every 6 months) Albendazole: Comparing 400 mg to 800 mg dose Diethylcarbamazine: Providing diethylcarbamazine more frequently in combination with albendazole
Overall Number of Participants Analyzed	13	13	10
Median (Full Range); Unit of Measure: MF/ML
	0; (0 to 0)	0; (0 to 0)	0; (0 to 0)

4. Secondary Outcome

Title	Brugia Specific Immunoglobulin G4 (IgG4) Antibodies
Description	IgG4 antibodies directed against Brugia malayi antigen
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

By 2 years, 4 subjects in High Dose Group lost to followup

Arm/Group Title	Standard Therapy Annual DEC/ALB	High Dose Annual DEC/ALB	High Dose Semiannual DEC/ALB
Arm/Group Description:	Group randomized to standard therapy that consists of Annual diethylcarbamazine (300 mg) and albendazole (400mg)	Group randomized to yearly high dose albendazole that consists of Annual diethylcarbamazine (300 mg) and albendazole (800mg)	Group randomized to twice-yearly high dose albendazole that consists of Annual diethylcarbamazine (300 mg) and albendazole (800mg)
Overall Number of Participants Analyzed	13	13	10
Median (Full Range); Unit of Measure: ng/ml
	150; (0 to 1000)	224; (0 to 2100)	128; (0 to 650)

Adverse Events

Time Frame	Every 6 months
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Standard Therapy Annual DEC/ALB		High Dose Annual DEC/ALB		High Dose Semiannual DEC/AC=LB
Arm/Group Description	Group randomized to standard therapy that consists of Annual diethylcarbamazine (300 mg) and albendazole (400mg)		Group randomized to yearly high dose albendazole that consists of Annual diethylcarbamazine (300 mg) and albendazole (800mg)		Group randomized to twice-yearly high dose albendazole that consists of Annual diethylcarbamazine (300 mg) and albendazole (800mg)
All-Cause Mortality
	Standard Therapy Annual DEC/ALB		High Dose Annual DEC/ALB		High Dose Semiannual DEC/AC=LB
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--
Serious Adverse Events
	Standard Therapy Annual DEC/ALB		High Dose Annual DEC/ALB		High Dose Semiannual DEC/AC=LB
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0.00%)		0/13 (0.00%)		0/14 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Standard Therapy Annual DEC/ALB		High Dose Annual DEC/ALB		High Dose Semiannual DEC/AC=LB
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/13 (69.23%)		8/13 (61.54%)		11/14 (78.57%)
Gastrointestinal disorders
Nausea/Vomiting * 1	1/13 (7.69%)	1	1/13 (7.69%)	1	0/14 (0.00%)	0
Investigations
Fever * 1	5/13 (38.46%)	5	4/13 (30.77%)	4	4/14 (28.57%)	4
Musculoskeletal and connective tissue disorders
Myalgia * 1	9/13 (69.23%)	9	8/13 (61.54%)	8	11/14 (78.57%)	11
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, Custom

Limitations and Caveats

Study never fully enrolled so sample size was smaller than hoped for.

More Information

Certain Agreements

Principal Investigators are NOT 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.

Results Point of Contact

• Name/Title: Thomas B. Nutman
• Organization: NIAID
• Phone: 301-496-5398
• EMail: tnutman@niaid.nih.gov

Publications:

Edwards G, Awadzi K, Breckenridge AM, Gilles HM, Orme ML, Ward SA. Diethylcarbamazine disposition in patients with onchocerciasis. Clin Pharmacol Ther. 1981 Oct;30(4):551-7.

Taylor HR, Greene BM. Ocular changes with oral and transepidermal diethylcarbamazine therapy of onchocerciasis. Br J Ophthalmol. 1981 Jul;65(7):494-502.

Partono F, Purnomo, Oemijati S, Soewarta A. The long term effects of repeated diethylcarbamazine administration with special reference to microfilaraemia and elephantiasis. Acta Trop. 1981 Sep;38(3):217-25.

• Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
• ClinicalTrials.gov Identifier: NCT00511004 History of Changes
• Other Study ID Numbers: 999907197; 07-I-N197 ( Other Identifier: NIAID IRB )
• First Submitted: August 2, 2007
• First Posted: August 3, 2007
• Results First Submitted: July 2, 2015
• Results First Posted: August 31, 2015
• Last Update Posted: August 31, 2015