East New Britain Province Monitoring & Evaluation

Acceptability of Mass Drug Administration for Lymphatic Filariasis Clinical Trial

— ENBP M&E  

Official title:

When is it Appropriate to Stop? Applied Field Research to Develop an M&E Strategy to

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04124250
• Other study ID #: STUDY20191141
• Status: Recruiting
• Start date: September 17, 2019
• Est. completion date: September 1, 2026

Study information

• Verified date: October 2023
• Source: University Hospitals Cleveland Medical Center
• Contact: Christopher L King, MD Ph.D.
• Phone: 216 368 4817
• Email: cxk21[@]case.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

While tremendous progress towards elimination of lymphatic filariasis (LF) has been made in the 20 years since the 1997 Fiftieth World Health Assembly, it is unlikely the goal of eliminating LF as a public health problem by 2020 will be achieved. As of 2016, it was estimated that 856 million people are still living in areas with ongoing transmission of LF and require mass drug administration (MDA) [1]. Of the 52 countries that remain endemic and require MDA, 22 (42%) have not started MDA in all endemic implementation units (IUs) [1]. In addition, several countries have found that, despite completing the required number of treatment rounds, the response to the present MDA regimen has been suboptimal in some IUs, requiring additional rounds of MDA.

Description:

Although the current two-drug regimen has been successful in many places, it is clear that augmented treatment regimens, other alternative strategies, or both are needed to accelerate global elimination. Fortunately, recent scientific studies, led by the DOLF project at Washington University in St. Louis, found that a three-drug regimen, using all three of the medicines typically delivered as a standard two-drug regimen to prevent LF (ivermectin + albendazole or diethycarbamazine + albendazole), is dramatically more effective for achieving sustained clearance of microfilariae from infected persons [2]. WHO conducted a rigorous and thorough review process of data from safety and efficacy trials of the triple drug regimen. In November, 2017, WHO endorsed and provided updated treatment guidelines that endorsed the use of IDA as a MDA regimen for LF elimination programs [3]. Following WHO's formal approval and release of the alternative treatment guidelines, in late November Merck & Co. committed to increase its Mectizan donation by 100 million treatments annually to eliminate LF [4], making the IDA regimen financially feasible for countries to adopt.

According to the recently published guidelines, WHO recommends the use of annual IDA in settings where onchocerciasis is not co-endemic with LF in districts have not yet started MDA, in areas that have received fewer than 4 effective rounds of MDA, and in areas where MDA results have been suboptimal. These guidelines call for the current epidemiological criteria (<1% microfilaremia or <2% antigenemia) to be applied to sentinel and spot check sites to determine whether the IU is eligible to proceed with the transmission assessment survey (TAS) and for the TAS to be used to base MDA-stopping decisions [3]. While the TAS has proven to be an effective tool for basing stopping decisions under the standard two-drug regimens, it is unclear whether the target age group (6-7 year olds) and epidemiologic target (<2% antigenemia in areas with W. bancrofti and <2% BmR1 antibodies in areas with Brugia spp. infections) are appropriate when IDA is used. Because IDA will result in an accelerated interruption of transmission and because the effects of this regimen on adult worms are not yet fully understood, it is possible that new target populations, infection indicators, sampling strategies, and/or thresholds will be required to determine when it is safe to stop IDA.

The purpose of this protocol is to describe the operational research (OR) that is necessary to develop a set of recommendations for WHO to consider regarding appropriate monitoring and evaluation (M&E) strategies for countries implementing IDA. Generating the information necessary to establish robust M&E guidelines requires a significant OR effort to ensure that all relevant information is collected, innovative strategies are considered, and that the ultimate recommendations are supported by evidence across multiple countries. It is important to emphasize that the study design described in this protocol is not what would be recommended of all countries implementing IDA. This protocol is for OR purposes only, with the goal that study findings will lead to a simplified M&E framework that is feasible for use by national LF elimination programs.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10500
• Est. completion date: September 1, 2026
• Est. primary completion date: September 1, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 5 Years to 80 Years

Eligibility

Inclusion Criteria:

• All individuals ages 5 years to 80 years living in selected villages will be eligible to enroll.

• Must live in the villages for at least 12 months

Exclusion Criteria:

• Minors ages 4 and under will not be eligible to enroll.

• Lived in selected village for less than 12 months.

Related Conditions & MeSH terms

• Acceptability of Mass Drug Administration for Lymphatic Filariasis
• Filariasis
• Lymphatic Filariasis Elimination by Mass Drug Administration
• Monitoring and Evaluation of Mass Drug Administration for Lymphatic Filariasis

Intervention

Other:
• Observational
Mass Drug Administration with a single co-administered dose of Ivermectin, DEC and Albendazole performed by Provincial and National Health Departments annually for two years

Locations

Country	Name	City	State
Papua New Guinea	East New Britain Provincial Health Authority	Kokopo	East New Britain Province

Sponsors (6)

Lead Sponsor	Collaborator
University Hospitals Cleveland Medical Center	Case Western Reserve University, Papua New Guinea ENB Provincial Health Authority, Papua New Guinea Institute for Medical Research, Papua New Guinea National Department of Health, Washington University School of Medicine

Country where clinical trial is conducted

Papua New Guinea, 

References & Publications (4)

Fischer PU, King CL, Jacobson JA, Weil GJ. Potential Value of Triple Drug Therapy with Ivermectin, Diethylcarbamazine, and Albendazole (IDA) to Accelerate Elimination of Lymphatic Filariasis and Onchocerciasis in Africa. PLoS Negl Trop Dis. 2017 Jan 5;11( — View Citation

Irvine MA, Stolk WA, Smith ME, Subramanian S, Singh BK, Weil GJ, Michael E, Hollingsworth TD. Effectiveness of a triple-drug regimen for global elimination of lymphatic filariasis: a modelling study. Lancet Infect Dis. 2017 Apr;17(4):451-458. doi: 10.1016 — View Citation

Rao RU, Nagodavithana KC, Samarasekera SD, Wijegunawardana AD, Premakumara WD, Perera SN, Settinayake S, Miller JP, Weil GJ. A comprehensive assessment of lymphatic filariasis in Sri Lanka six years after cessation of mass drug administration. PLoS Negl T — View Citation

Schmaedick MA, Koppel AL, Pilotte N, Torres M, Williams SA, Dobson SL, Lammie PJ, Won KY. Molecular xenomonitoring using mosquitoes to map lymphatic filariasis after mass drug administration in American Samoa. PLoS Negl Trop Dis. 2014 Aug 14;8(8):e3087. d — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the presence of W. bancrofti microfilariae	Perform blood smears of venous blood collected at night	3 years
Primary	To determine the presence of W. bancrofti circulating antigen	Fingerstick blood will be collected to assess the presence and semi-quantitative levels of circulating filarial antigen using Alere filarial test strips	3 years
Secondary	To determine the presence and frequency anopheline mosquitos infected with lymphatic filariasis (Xenomonitoring)	Mosquitoes will be collected by light traps or human landing catches, anopheline mosquitoes separated, pooled and DNA extracted and the presence of W. bancrofti DNA assessed by PCR	3 years
Secondary	To determine the knowledge and attitudes about lymphatic filariasis and acceptability of the mass drug program for lymphatic filariasis	Prior to mass drug treatment and following treatment randomly selected individuals will be asked to complete a questionnaire and subset of individuals interviewed	2 years

External Links

•   Merck Commemorates 30 Years of MECTIZAN® Donation Program Progress | Merck Newsroom Home
•   World Health Organization. Alternative mass drug administration regimens to eliminate lymphatic filariasis. 2017;