Lymphatic Filariasis (LF) in Ivory Coast

NCT02974049 | Completed DMC

• 1 other identifier: 08-14-13
• Study Type: interventional
• Target: 189
• Locations: 1 country
• Sites: 1

Brief Summary

The recommended treatment for elimination of LF in sub-Saharan Africa is annual mass drug administration (MDA) with single dose Albendazole (ALB) plus Ivermectin (IVM) given for at least 5-7 years. However, in areas where LF is co-endemic with a related filarial parasite, Loa loa, co-infection with L. loa represents a serious barrier to LF elimination because IVM used in LF MDA can result in severe reactions and even death in individuals with high microfilaria (mf) levels of L. loa. Screening for heavy L. loa infection is problematic. To overcome this problem, monotherapy with ALB is possible, since this drug has little or no effect on circulating mf and thus would not cause adverse effects in people with heavy L. loa infections. Moreover ALB has been shown to have embryostatic or embryocidal effects in female adult worms resulting in decreased mf levels with time as natural attrition of circulating mf occurs. Thus this open-label, randomized clinical trial will examine treatment with ALB monotherapy administered twice per year over a period of 3 years with the primary endpoint being the proportion of individuals with total clearance of mf at 36 months and Alere antigen test negativity (a more sensitive circulating antigen test of filarial infection). Two of the treatment arms will include ALB at two different doses, 400mg or 800mg (fixed dose twice yearly) as compared to standard treatment of ALB (400 mg) plus IVM (150-200 µg/kg) administered annually. Observations from an ongoing clinical trial in Papua New Guinea suggest that a single dose of triple therapy with ALB + IVM + DEC may be highly effective in sterilizing adult female worms. Therefore to confirm and expand these important preliminary observations in a different population, a fourth arm will be included in the current clinical trial in which subjects will receive all three drugs. The clinical trial will be performed in a region of Cote d'Ivoire where onchocerciasis and loiasis are not endemic.

Conditions

Lymphatic Filariasis

Keywords

Ivermectin; Albendazole; Diethylcarbamazine

Outcome Measures

Primary Outcomes (1)

• Total clearance of Microfilariae

  The percentage of participants with total clearance of Microfilariae

  36 months

Secondary Outcomes (7)

• Total clearance of MF at 24 months

  24 months

• Percent MF reduction

  24 and 36 months

• Reduction in W. bancrofti antigen level

  12, 24 and 36 months

• Alere Filariasis Test Strip negative

  12, 24 and 36 months

• reduction in viable worm nests

  12, 24, and 36 months

Study Arms (4)

Standard Treatment

ACTIVE COMPARATOR

Albendazole 400 mg + Ivermectin 200 µg/kg body weight administered annually (at 0, 12 and 24 months)

Drug: Albendazole; Drug: Ivermectin

ALB 400 mg x2 per year

EXPERIMENTAL

Albendazole 400 mg given at 0, 6, 12, 18, 24 and 30 months

Drug: Albendazole

ALB 800 mg x2 per year

EXPERIMENTAL

Albendazole 800 mg given at 0, 6, 12, 18, 24 and 30 months

Drug: Albendazole

ALB 400mg + IVM 200mcg/kg + DEC 6mg/kg

EXPERIMENTAL

Albendazole 400 mg plus Ivermectin 200 µg/kg body weight plus Diethylcarbamazine 6 mg/kg body weight given one time only

Drug: Albendazole; Drug: Ivermectin; Drug: Diethylcarbamazine

Interventions

Albendazole DRUG

Subjects in Arms 1, 2, and 4 will receive 400mg of Albendazole Subjects in Arm 3 will receive 800mg of Albendazole

Also known as: ALB

ALB 400 mg x2 per year; ALB 400mg + IVM 200mcg/kg + DEC 6mg/kg; ALB 800 mg x2 per year; Standard Treatment

Ivermectin DRUG

Subjects in Arms 1 and 4 will receive 200mg/kg body weight

Also known as: IVM

ALB 400mg + IVM 200mcg/kg + DEC 6mg/kg; Standard Treatment

Diethylcarbamazine DRUG

Participants in Arm 4 will receive 6mg/kg of Diethylcarbamazine per body weight

Also known as: DEC

ALB 400mg + IVM 200mcg/kg + DEC 6mg/kg

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women and men 18-70 years
• ≥50 MF/mL based on Nuclepore filtration
• Willing to give informed consent

You may not qualify if:

• Prior treatment for LF within last 5 years
• Pregnancy (perform pregnancy test)
• Hemoglobin \<7 g/dL
• Permanent disability, serious medical illness that prevents or impedes study participation and/or comprehension
• AST/ALT and creatinine \>1.5 upper limit of normal
• Proteinuria or hematuria \>3+
• Skin snip positivity for O. volvulus MF

Sponsors & Collaborators

• University Hospitals Cleveland Medical Center: lead
• Washington University School of Medicine: collaborator

Study Sites (1)

Cote d'Ivoire

Abidjan, Côte d’Ivoire

Location

Related Publications (24)

• Awadzi K, Edwards G, Duke BO, Opoku NO, Attah SK, Addy ET, Ardrey AE, Quartey BT. The co-administration of ivermectin and albendazole--safety, pharmacokinetics and efficacy against Onchocerca volvulus. Ann Trop Med Parasitol. 2003 Mar;97(2):165-78. doi: 10.1179/000349803235001697.

  PMID: 12803872 BACKGROUND

• Awadzi K, Edwards G, Opoku NO, Ardrey AE, Favager S, Addy ET, Attah SK, Yamuah LK, Quartey BT. The safety, tolerability and pharmacokinetics of levamisole alone, levamisole plus ivermectin, and levamisole plus albendazole, and their efficacy against Onchocerca volvulus. Ann Trop Med Parasitol. 2004 Sep;98(6):595-614. doi: 10.1179/000349804225021370.

  PMID: 15324466 BACKGROUND

• Bockarie MJ, Tavul L, Ibam I, Kastens W, Hazlett F, Tisch DJ, Alpers MP, Kazura JW. Efficacy of single-dose diethylcarbamazine compared with diethylcarbamazine combined with albendazole against Wuchereria bancrofti infection in Papua New Guinea. Am J Trop Med Hyg. 2007 Jan;76(1):62-6.

  PMID: 17255231 BACKGROUND

• Boussinesq M, Kamgno J, Pion SD, Gardon J. What are the mechanisms associated with post-ivermectin serious adverse events? Trends Parasitol. 2006 Jun;22(6):244-6. doi: 10.1016/j.pt.2006.04.006. Epub 2006 Apr 24. No abstract available.

  PMID: 16632406 BACKGROUND

• Chu, B. K., P. J. Hooper, M. H. Bradley, D. A. McFarland and E. A. Ottesen

  BACKGROUND

• Geary TG. Ivermectin 20 years on: maturation of a wonder drug. Trends Parasitol. 2005 Nov;21(11):530-2. doi: 10.1016/j.pt.2005.08.014. Epub 2005 Aug 26.

  PMID: 16126457 BACKGROUND

• Ottesen EA. Lymphatic filariasis: Treatment, control and elimination. Adv Parasitol. 2006;61:395-441. doi: 10.1016/S0065-308X(05)61010-X.

  PMID: 16735170 BACKGROUND

• Geary TG, Mackenzie CD. Progress and challenges in the discovery of macrofilaricidal drugs. Expert Rev Anti Infect Ther. 2011 Aug;9(8):681-95. doi: 10.1586/eri.11.76.

  PMID: 21819332 BACKGROUND

• Hoerauf A, Pfarr K, Mand S, Debrah AY, Specht S. Filariasis in Africa--treatment challenges and prospects. Clin Microbiol Infect. 2011 Jul;17(7):977-85. doi: 10.1111/j.1469-0691.2011.03586.x.

  PMID: 21722251 BACKGROUND

• Hooper PJ, Bradley MH, Biswas G, Ottesen EA. The Global Programme to Eliminate Lymphatic Filariasis: health impact during its first 8 years (2000-2007). Ann Trop Med Parasitol. 2009 Oct;103 Suppl 1:S17-21. doi: 10.1179/000349809X12502035776513.

  PMID: 19843394 BACKGROUND

• Horton J. Albendazole: a broad spectrum anthelminthic for treatment of individuals and populations. Curr Opin Infect Dis. 2002 Dec;15(6):599-608. doi: 10.1097/00001432-200212000-00008.

  PMID: 12821837 BACKGROUND

• Horton J. The development of albendazole for lymphatic filariasis. Ann Trop Med Parasitol. 2009 Oct;103 Suppl 1:S33-40. doi: 10.1179/000349809X12502035776595.

  PMID: 19843396 BACKGROUND

• Hotez PJ, Savioli L, Fenwick A. Neglected tropical diseases of the Middle East and North Africa: review of their prevalence, distribution, and opportunities for control. PLoS Negl Trop Dis. 2012;6(2):e1475. doi: 10.1371/journal.pntd.0001475. Epub 2012 Feb 28.

  PMID: 22389729 BACKGROUND

• Kitzman D, Wei SY, Fleckenstein L. Liquid chromatographic assay of ivermectin in human plasma for application to clinical pharmacokinetic studies. J Pharm Biomed Anal. 2006 Mar 3;40(4):1013-20. doi: 10.1016/j.jpba.2005.08.026. Epub 2005 Oct 19.

  PMID: 16242280 BACKGROUND

• Mand S, Debrah A, Batsa L, Adjei O, Hoerauf A. Reliable and frequent detection of adult Wuchereria bancrofti in Ghanaian women by ultrasonography. Trop Med Int Health. 2004 Oct;9(10):1111-4. doi: 10.1111/j.1365-3156.2004.01304.x.

  PMID: 15482404 BACKGROUND

• McGarry HF, Plant LD, Taylor MJ. Diethylcarbamazine activity against Brugia malayi microfilariae is dependent on inducible nitric-oxide synthase and the cyclooxygenase pathway. Filaria J. 2005 Jun 2;4:4. doi: 10.1186/1475-2883-4-4.

  PMID: 15932636 BACKGROUND

• Moreno Y, Nabhan JF, Solomon J, Mackenzie CD, Geary TG. Ivermectin disrupts the function of the excretory-secretory apparatus in microfilariae of Brugia malayi. Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):20120-5. doi: 10.1073/pnas.1011983107. Epub 2010 Nov 1.

  PMID: 21041637 BACKGROUND

• Ottesen EA, Duke BO, Karam M, Behbehani K. Strategies and tools for the control/elimination of lymphatic filariasis. Bull World Health Organ. 1997;75(6):491-503.

  PMID: 9509621 BACKGROUND

• Ottesen EA, Hooper PJ, Bradley M, Biswas G. The global programme to eliminate lymphatic filariasis: health impact after 8 years. PLoS Negl Trop Dis. 2008 Oct 8;2(10):e317. doi: 10.1371/journal.pntd.0000317.

  PMID: 18841205 BACKGROUND

• Teruel M, Dercole J, Catalano R. Evaluation of potential embryo toxicity of albendazole sulphoxide in CF1 mice. Biocell. 2011 Apr;35(1):29-33.

  PMID: 21667669 BACKGROUND

• Weil GJ, Curtis KC, Fakoli L, Fischer K, Gankpala L, Lammie PJ, Majewski AC, Pelletreau S, Won KY, Bolay FK, Fischer PU. Laboratory and field evaluation of a new rapid test for detecting Wuchereria bancrofti antigen in human blood. Am J Trop Med Hyg. 2013 Jul;89(1):11-15. doi: 10.4269/ajtmh.13-0089. Epub 2013 May 20.

  PMID: 23690552 BACKGROUND

• Zoure HG, Wanji S, Noma M, Amazigo UV, Diggle PJ, Tekle AH, Remme JH. The geographic distribution of Loa loa in Africa: results of large-scale implementation of the Rapid Assessment Procedure for Loiasis (RAPLOA). PLoS Negl Trop Dis. 2011 Jun;5(6):e1210. doi: 10.1371/journal.pntd.0001210. Epub 2011 Jun 28.

  PMID: 21738809 BACKGROUND

• Ouattara AF, Bjerum CM, Aboulaye M, Kouadio O, Marius VK, Andersen B, Lew D, Goss CW, Weil GJ, Koudou BG, King CL. Semiannual Treatment of Albendazole Alone is Efficacious for Treatment of Lymphatic Filariasis: A Randomized Open-label Trial in Cote d'Ivoire. Clin Infect Dis. 2022 Jul 6;74(12):2200-2208. doi: 10.1093/cid/ciab194.

  PMID: 33674871 DERIVED

• Bjerum CM, Ouattara AF, Aboulaye M, Kouadio O, Marius VK, Andersen BJ, Weil GJ, Koudou BG, King CL. Efficacy and Safety of a Single Dose of Ivermectin, Diethylcarbamazine, and Albendazole for Treatment of Lymphatic Filariasis in Cote d'Ivoire: An Open-label Randomized Controlled Trial. Clin Infect Dis. 2020 Oct 23;71(7):e68-e75. doi: 10.1093/cid/ciz1050.

  PMID: 31641754 DERIVED

MeSH Terms

Conditions

Elephantiasis, Filarial

Interventions

Albendazole; Ivermectin; Diethylcarbamazine

Condition Hierarchy (Ancestors)

Filariasis; Spirurida Infections; Secernentea Infections; Nematode Infections; Helminthiasis; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Lymphedema; Lymphatic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Macrolides; Polyketides; Lactones; Piperazines; Heterocyclic Compounds, 1-Ring

Study Officials

• Christopher L King, MD PhD

  Case Western Reserve University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of International Health, Medicine and Pathology

Study Record Dates

• First Submitted: November 22, 2016
• First Posted: November 28, 2016
• Study Start: January 1, 2015
• Primary Completion: September 1, 2018
• Study Completion: September 25, 2018
• Last Updated: April 21, 2022

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will share

Locations

CÔ (1)