Lymphatic Filariasis Clinical Trial
Official title:
Community Based Safety Study of 2-drug (Diethylcarbamazine and Albendazole) Versus 3-drug (Ivermectin, Diethylcarbamazine and Albendazole) Therapy for Lymphatic Filariasis
NCT number | NCT02899936 |
Other study ID # | 201607068 |
Secondary ID | |
Status | Completed |
Phase | N/A |
First received | |
Last updated | |
Start date | July 2016 |
Est. completion date | May 31, 2018 |
Verified date | December 2020 |
Source | Washington University School of Medicine |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
The DOLF Triple Drug Therapy for Lymphatic Filariasis study will determine the frequency, type and severity of adverse events following triple-drug therapy (IVM+DEC+ALB, IDA) compared to the standard two-drug treatment (DEC+ALB, DA) in infected and uninfected individuals in a community in 5 different countries. The objective is to acquire safety, efficacy, and acceptability data to assess the safety and acceptability of the IDA drug combination.
Status | Completed |
Enrollment | 23789 |
Est. completion date | May 31, 2018 |
Est. primary completion date | April 27, 2017 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 2 Years and older |
Eligibility | In India: Inclusion Criteria: 1. Age = 5 years, male or female for IDA arm and age > 2 years for DA arm. 2. Able to provide informed consent to participate in the trial (forms to be attached) 3. No evidence of severe or systemic co-morbidities except for features of filarial disease Exclusion Criteria: 1. Age < 5 years (ivermectin is contraindicated in children below 5 years of age) for IDA arm and age < 2 years for DA arm 2. Pregnant women (DEC, ivermectin and albendazole are contraindicated in pregnancy) 3. Severe chronic illness (for example, chronic renal failure, inability to care for oneself with activities of daily living) 4. History of previous allergy to MDA drugs For rest of countries: Inclusion Criteria: 1. Age = 5 years, for IDA and DA arms (males and females). 2. Able to provide informed consent or give parental consent for minors to participate in the trial 3. No evidence of severe or systemic co-morbidities except for features of filarial disease Exclusion Criteria: 1. Age < 5 years (ivermectin is not approved for use in children less than 5 years of age) 2. Unable to provide informed consent or give parental consent for minors to participate in the trial 3. Pregnant women (DEC, ivermectin and albendazole are not known to be safe for use during pregnancy) 4. Severe chronic illness (chronic renal insufficiency, severe chronic liver disease, or any illness that is severe enough to interfere with activities of daily living) 5. History of previous allergy to MDA drugs |
Country | Name | City | State |
---|---|---|---|
Haiti | Ministere de la Sante Publique et de la Population | Port-au-Prince | |
India | Vector Control Research Centre | Puducherry | |
Indonesia | Universitas Indonesia | Jakarta | |
Papua New Guinea | Papua New Guinea Institute for Medical Research | Madang |
Lead Sponsor | Collaborator |
---|---|
Washington University School of Medicine | Case Western Reserve University, Indian Council of Medical Research |
Haiti, India, Indonesia, Papua New Guinea,
489 Global programme to eliminate lymphatic filariasis: progress report, 2014. Wkly Epidemiol Rec. 2015 Sep 18;90(38):489-504. English, French. — View Citation
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. — View Citation
de Rochars MB, Kanjilal S, Direny AN, Radday J, Lafontant JG, Mathieu E, Rheingans RD, Haddix AC, Streit TG, Beach MJ, Addiss DG, Lammie PJ. The Leogane, Haiti demonstration project: decreased microfilaremia and program costs after three years of mass drug administration. Am J Trop Med Hyg. 2005 Nov;73(5):888-94. — View Citation
Edwards G. Ivermectin: does P-glycoprotein play a role in neurotoxicity? Filaria J. 2003 Oct 24;2 Suppl 1:S8. — View Citation
Goa KL, McTavish D, Clissold SP. Ivermectin. A review of its antifilarial activity, pharmacokinetic properties and clinical efficacy in onchocerciasis. Drugs. 1991 Oct;42(4):640-58. Review. — View Citation
Gyapong JO, Kumaraswami V, Biswas G, Ottesen EA. Treatment strategies underpinning the global programme to eliminate lymphatic filariasis. Expert Opin Pharmacother. 2005 Feb;6(2):179-200. Review. — View Citation
Horton J. Albendazole: a review of anthelmintic efficacy and safety in humans. Parasitology. 2000;121 Suppl:S113-32. Review. — View Citation
Norões J, Dreyer G, Santos A, Mendes VG, Medeiros Z, Addiss D. Assessment of the efficacy of diethylcarbamazine on adult Wuchereria bancrofti in vivo. Trans R Soc Trop Med Hyg. 1997 Jan-Feb;91(1):78-81. — View Citation
Oscar R, Lemoine JF, Direny AN, Desir L, Beau de Rochars VE, Poirier MJ, Varghese A, Obidegwu I, Lammie PJ, Streit TG, Milord MD. Haiti National Program for the elimination of lymphatic filariasis--a model of success in the face of adversity. PLoS Negl Trop Dis. 2014 Jul 17;8(7):e2915. doi: 10.1371/journal.pntd.0002915. eCollection 2014 Jul. — View Citation
Ottesen EA, Campbell WC. Ivermectin in human medicine. J Antimicrob Chemother. 1994 Aug;34(2):195-203. Review. — View Citation
Ottesen EA. Efficacy of diethylcarbamazine in eradicating infection with lymphatic-dwelling filariae in humans. Rev Infect Dis. 1985 May-Jun;7(3):341-56. — View Citation
Thomsen EK, Sanuku N, Baea M, Satofan S, Maki E, Lombore B, Schmidt MS, Siba PM, Weil GJ, Kazura JW, Fleckenstein LL, King CL. Efficacy, Safety, and Pharmacokinetics of Coadministered Diethylcarbamazine, Albendazole, and Ivermectin for Treatment of Bancroftian Filariasis. Clin Infect Dis. 2016 Feb 1;62(3):334-341. doi: 10.1093/cid/civ882. Epub 2015 Oct 20. — View Citation
World Health Organization (1997). Elimination of lymphatic filariasis as a public health problem - resolution of the executive board of the WHO.
* Note: There are 13 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Number of participants with treatment-related adverse events as assessed by modified CTCAE v4.0 scale | To determine the frequency, type and severity of adverse events following triple-drug therapy Ivermectin, Diethylcarbamazine and Albendazole (IVM+DEC+ALB, IDA) compared to the standard two-drug treatment Diethylcarbamazine and Albendazole (DEC+ALB, DA) in infected and uninfected individuals in a community as assessed by modified CTCAE v4.0 scale. | within 7 days of drug administration | |
Secondary | Number of participants with clearance of microfilaremia (MF) as measured with microfilaremia night blood smear testing (finger prick - 60ul) | To compare the efficacy of IDA vs. DA administered in communities for clearance of MF and filarial antigenemia (Ag) in cohort and effectiveness (prevalence) in community settings. A minimum of 21 (70%) of MF-positive participants in each arm will be retested at 12 months post-treatment for antigenemia and microfilaremia. This sample size is adequate to demonstrate superiority of the IDA regimen (assumptions: 90% reduction in MF prevalence after IDA and 60% reduction after DA, 80% power for detecting an effect size of 30%). The primary endpoint for efficacy will be complete clearance of MF 12 months post Mass Drug Administration (MDA). Clearance of filarial antigenemia at 12 months will be a secondary endpoint for the efficacy analysis. Testing of microfilaria is by analyzing 60 microliter (ul) measured volume thick blood smear by finger prick method and results are either positive or negative for MF presence. | baseline (pre-treatment), within 7 days of drug administration and follow up at 12 months | |
Secondary | Number of participants Filarial Test Strip (FTS) and/or MF positive as tested with FTS and night blood smears with treatment-related adverse events as assessed by modified CTCAE v4.0 scale | To assess the presence and intensity of filarial infection on the frequency and severity of adverse events. One year post MDA, all participants who were positive for either microfilaremia or filarial antigenemia during the baseline visit will be tested for filarial antigen using the FTS to assess their response to treatment and to compare the efficacy of the two treatment regimens. Participants with positive FTS will also be tested for nocturnal microfilaremia by blood smear (finger prick - 60ul) | baseline (pre-treatment), within 7 days of drug administration and follow up at 12 months | |
Secondary | Community acceptance will be measured using on a survey using likert scale questions based on perception of efficacy, intent to participate and relevance of the treatment. | Community acceptance will be measured using a survey to community members receiving both the 2-drug and 3-drug treatments during the safety trial. To complement this survey, a series of focus group discussions in the community as well as key informant interviews are proposed with community leaders, health personnel and drug distributors in the same communities to assess perceptions about the 3-drug versus the 2-drug regimen. The community acceptability study will be carried out within one month of the completion of the safety trial. The acceptability score will use a set of likert scale questions based on perception of efficacy, intent to participate and relevance of the treatment. Some of the questions have been inspired by Reimer's Treatment Acceptability Rating form-Revised and general principles of social validity but mostly the questions are not from one particular survey instrument. | 6-8 months | |
Secondary | Prevalence of STH (hookworm, ascaris, trichuris and strongyloides) as measured by Kato-katz or PCR at baseline and 12 months after treatment | Some sites will include stool sample collections to compare the efficacy of 2 and 3-drug regimens on STH. Stool samples will be analysed using Kato-katz method, as well as PCR. | Stool collected at baseline (pre-treatment), 4 weeks (individual response), and 12 months (community prevalence). |
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