Clinical trial NCT04124250: East New Britain Province Monitoring & Evaluation
Official title: When is it Appropriate to Stop? Applied Field Research to Develop an M&E Strategy to
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Lymphatic Filariasis Elimination by Mass Drug Administration
Monitoring and Evaluation of Mass Drug Administration for Lymphatic Filariasis
Acceptability of Mass Drug Administration for Lymphatic Filariasis
Lead sponsor: University Hospitals Cleveland Medical Center
Sponsor class: OTHER
Collaborators: name: Case Western Reserve University
name: Washington University School of Medicine
name: Papua New Guinea Institute for Medical Research
name: Papua New Guinea ENB Provincial Health Authority
name: Papua New Guinea National Department of Health
First posted: 2019-10-11
Enrollment: 12930
Sex: ALL
Minimum age (years): 5
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: ECOLOGIC_OR_COMMUNITY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Two distinct age groups will be sampled as part of each assessment: children 5-9 years old and adolescents and adults \>10 years. The child and adult surveys will be conducted in the same selected clusters; however, the adult survey will be conducted in a subset of the households (HHs) selected for the child survey because there are likely to be more eligible adults per HH than children.

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: To determine the presence of W. bancrofti microfilariae
timeFrame: 3 years
measure: To determine the presence of W. bancrofti circulating antigen
timeFrame: 3 years
Secondary outcomes:
measure: To determine the presence and frequency anopheline mosquitos infected with lymphatic filariasis (Xenomonitoring)
timeFrame: 3 years
measure: To determine the knowledge and attitudes about lymphatic filariasis and acceptability of the mass drug program for lymphatic filariasis
timeFrame: 2 years
Other outcomes:
Locations:
city: Kokopo
country: Papua New Guinea
facility: East New Britain Provincial Health Authority
state: East New Britain Province
Study officials:
References:
citation: 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(1):e0005163. doi: 10.1371/journal.pntd.0005163. eCollection 2017 Jan. No abstract available.
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/S1473-3099(16)30467-4. Epub 2016 Dec 22.
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. doi: 10.1371/journal.pntd.0003087. eCollection 2014 Aug.
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 Trop Dis. 2014 Nov 13;8(11):e3281. doi: 10.1371/journal.pntd.0003281. eCollection 2014.