An interventional study of 3 drug dose - IDA and 2 drug dose - DA in Lymphatic Filariasis, sponsored by Washington University School of Medicine. Completed at 4 sites in 4 countries. Open to participants aged 2 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-12-31.
Sponsored by Washington University School of Medicine · Not applicable, Interventional, and Treatment
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.
In 2000, the World Health Organization (WHO) launched the Global Programme to Eliminate Lymphatic Filariasis (GPELF) to eliminate lymphatic filariasis as a public health problem by 2020. To interrupt transmission, WHO recommends therapy using combinations of two medicines delivered to entire at-risk populations through a strategy known as mass drug administration. Ivermectin (IVM) and albendazole (ALB) are administered in areas where onchocerciasis is co-endemic; diethylcarbamazine (DEC) and albendazole (ALB) are administered in areas where onchocerciasis is not co-endemic.
Results of a pilot study in Papua New Guinea suggest that triple drug therapy (ivermectin, diethylcarbamazine and albendazole) is superior to the currently recommended two-drug regimen (DEC+ALB, DA). A single dose of the triple therapy (IVM+DEC+ALB, IDA) rapidly achieved complete clearance of Wuchereria bancrofti microfilariae from the blood of 12 individuals for at least one year post-treatment. All six individuals tested at 24 months were still amicrofilaremic, suggesting that the triple therapy might permanently sterilizes adult filarial worms. Many people treated in these studies experienced transient systemic adverse events commonly associated with diethylcarbamazine or ivermectin treatment of filariasis. Adverse events were more frequent after the triple therapy than after the usual combination of two drugs. However, no serious adverse events were observed. The dramatic reduction and sustained decrease of microfilaria along with the safety profile seen in the Papua New Guinea studies suggest that the triple drug therapy may be a useful tool to achieve the goal of eliminating lymphatic filariasis as a public health problem by 2020.
Although the study cited above has clearly demonstrated the superiority of the triple therapy for clearing W. bancrofti microfilaria from the blood, more safety and efficacy data are needed before triple therapy can be rolled out on a large scale as a mass drug administration regimen in lymphatic filariasis endemic countries. WHO recommends a best practice called "cohort event monitoring" for demonstrating safety of new drug regimens for public health program use. Establishing safety through such methodology requires pre and post treatment assessment from at least 10,000 people treated with the triple therapy across multiple settings.
It is therefore proposed to conduct a cohort event monitoring study to acquire safety data. Efficacy and acceptability components will also be included in the study. Similar studies will be conducted simultaneously in Haiti, India, Indonesia, Papua New Guinea and Sri Lanka to reach the 10,000 people necessary to assess the safety of this new drug combination.
This will be an open label, two-armed study. The two arms are (1) mass drug administration (MDA) with the currently used combination of two-drug regimen (DA) and (2) MDA with triple drug therapy (IDA).
42 studies on the registry are indexed under Elephantiasis, Filarial; 5 are open to participants now.
This study's enrollment of 23,789 is above the median of 1,000 across 27 interventional studies indexed under Elephantiasis, Filarial.
Browse Elephantiasis, Filarial studies →Washington University School of Medicine is the lead sponsor of 1,803 studies on the registry; 271 are open to participants now.
Of its 329 completed or terminated interventional studies of FDA-regulated products, 216 (66%) have results posted.
Counted across the registry records on this site, refreshed daily.
In India:
Inclusion Criteria:
Exclusion Criteria:
For rest of countries:
Inclusion Criteria:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Drug treatment with two-drug regimen diethylcarbamazine and albendazole (DA)
Drug: 2 drug dose - DA
Triple-drug regimen Ivermectin, diethylcarbamazine and albendazole (IDA)
Drug: 3 drug dose - IDA
Lymphatic Filariasis Mass Drug Administration (MDA) with triple drug therapy of ivermectin, diethylcarbamazine, and albendazole (IDA)
Also known as: IDA
Lymphatic Filariasis Mass Drug Administration (MDA) with the currently used standard of care combination drug therapy of diethylcarbamazine, and albendazole (DA)
Also known as: DA
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.
Time frame: within 7 days of drug administration
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.
Time frame: baseline (pre-treatment), within 7 days of drug administration and follow up at 12 months
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)
Time frame: baseline (pre-treatment), within 7 days of drug administration and follow up at 12 months
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.
Time frame: 6-8 months
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.
Time frame: Stool collected at baseline (pre-treatment), 4 weeks (individual response), and 12 months (community prevalence).
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Datasets used for published results will be shared publically through a journal or other open source data repository so that the broader scientific community can access it. Only de-identified data will be shared publicly.
Time frame: Manuscripts should be submitted for publication no later than one year following the date of the "last patient/last visit". Some DOLF studies include follow-up studies that continue after the primary end point of the study. There is no need to wait for these studies to be completed in order to publish the primary data. (In the case of the IDA studies, safety data should be prepared for publication prior to the acceptability and efficacy studies.)
Access criteria: Investigators and their supporting institution that conduct research with financial support from Bill \& Melinda Gates Foundation (BMGF) will share de-identified data with partner scientists. Results from multiple study sites will be combined so that they can be considered in aggregate. Aggregated data and summary results may be shared with the World Health Org, BMGF, pharmaceutical donors, and others involved in the Global Prog to Eliminate Lymphatic Filariasis even prior to the publication of results. We will follow US National Institutes of Health (NIH) guidelines regarding data sharing with scientists outside of the project. Datasets used for published results will be shared publically through a journal or other open source data repository. De-identified data will be shared outside of DOLF. Data sharing requests from third-parties must have the approval of the local country PI. The study's primary results should be published before data will be shared with third-parties.
Data sharing details ↗ · grants.nih.gov
The record gives a start of Jul 2016, a primary completion of Apr 2017 and a completion of May 2018. It does not say whether these dates are actual or estimated.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Dec 2020. You cannot join it, but the record below documents what was studied.
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