Malaria Clinical Trial
— FLAMEOfficial title:
FocaL Mass Drug Administration for Vivax Malaria Elimination (FLAME): a Pragmatic Cluster Randomized Controlled Trial in Peru
FLAME is an open-label cluster-randomized controlled trial that aims to determine the effectiveness of focal mass drug administration (fMDA) to reduce the incidence of Plasmodium vivax malaria in the Loreto Department in Peru. Standard interventions, including symptomatic and asymptomatic screening for malaria infections, provision of insecticide-treated bednets, and environmental transmission monitoring, will be compared to clusters of villages randomized to receive anti-malarial drugs.
Status | Not yet recruiting |
Enrollment | 7700 |
Est. completion date | May 1, 2027 |
Est. primary completion date | May 1, 2027 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | N/A and older |
Eligibility | Inclusion Criteria: 1. Cluster eligibility - Within 8 hours transport of Iquitos - Incidence <250/1000 and >2 cases year prior to trial - Population size (<650) 2. Chloroquine (CQ) eligibility - Resides in neighboring household but within 200 m of Pv index case in the past 2 years - Age =6 months old - Present for intervention - Adult =18 years old that provides informed consent - A child =8 years and <18 years old that provides informed assent and has informed consent from their parents - A child =6 months old and <8 years old that has informed consent from their parents 3. Tafenoquine (TQ) eligibility - Eligible to receive CQ - Age =16 years old - Adult =18 years old that provides informed consent - A child =16 years and <18 years old that provides informed assent and has informed consent from their parents 4. Primaquine eligibility - Eligible to receive CQ and ineligible to receive TQ - Age =6 months old - Adult =18 years old that provides informed consent - A child =8 years and <18 years old that provides informed assent and has informed consent from their parents - A child =6 months old and <8 years old that has informed consent from their parents 5. Baseline evaluation and informed consent -Villagers will be eligible to participate in surveys if they slept in a household in cluster randomized to control or focal mass drug administration (fMDA) for at least one night in the past four weeks 6. Eligibility for fMDA - High-risk villagers are defined as individuals residing in households that are within 200 meters of a Plasmodium vivax index case households from the prior 2 years (including individuals in the index case household) will be eligible to receive fMDA that cycle - Villagers that were eligible but missed in the 1st annual round, or become eligible in the next two months, can receive fMDA in the 2nd annual round. Exclusion Criteria: 1. Chloroquine eligibility - History of retinal or visual field changes - Known hypersensitivity or adverse reaction to CQ - Currently taking CQ or have taken CQ in the past four weeks - Ineligible for TQ or PQ (see criteria below) - Hemoglobin <7 g/dL 2. Tafenoquine eligibility - G6PD deficiency or intermediate status (defined as activity =6.0 UI/gHb per SD biosensor) - G6PD status unknown or refusal of G6PD status test - Acute or severe malaria - Pregnancy (known or identified by pregnancy test) - Refusal of pregnancy test if new amenorrhea in the past 4 weeks - Woman breastfeeding a child that is G6PD deficient or with unknown G6PD status - Known hypersensitivity or adverse reaction to TQ or PQ - Have taken mefloquine (i.e. artesunate- mefloquine), TQ or PQ, or other antimalarial in the past four weeks - Hemoglobin < 7 g/dL 3. Primaquine eligibility - G6PD deficiency (defined as activity =4.0 UI/gHb per SD biosensor) - G6PD status unknown or refusal of G6PD status test - Acute or severe malaria - Pregnancy (known or identified by pregnancy test) - Refusal of pregnancy test if new amenorrhea in the past 4 weeks - Breastfeeding child with documented or unknown G6PD deficiency status - Known hypersensitivity or adverse reaction to TQ or PQ - Have taken mefloquine (i.e. artesunate- mefloquine), TQ or PQ, or other antimalarial in the past four weeks - Hemoglobin < 7 g/dL |
Country | Name | City | State |
---|---|---|---|
Peru | Universidad Peruana de Cayetano Heredia | Lima |
Lead Sponsor | Collaborator |
---|---|
University of California, San Francisco | Eijkman Oxford Clinical Research Unit, Indonesia, Menzies School of Health Research, National Institute of Allergy and Infectious Diseases (NIAID), PATH, Stanford University, Universidad Peruana Cayetano Heredia- subcontractor to UCSF as local Sponsor |
Peru,
Hsiang MS, Hwang J, Tao AR, Liu Y, Bennett A, Shanks GD, Cao J, Kachur SP, Feachem RG, Gosling RD, Gao Q. Mass drug administration for the control and elimination of Plasmodium vivax malaria: an ecological study from Jiangsu province, China. Malar J. 2013 Nov 1;12:383. doi: 10.1186/1475-2875-12-383. — View Citation
Hsiang MS, Ntuku H, Roberts KW, Dufour MK, Whittemore B, Tambo M, McCreesh P, Medzihradsky OF, Prach LM, Siloka G, Siame N, Gueye CS, Schrubbe L, Wu L, Scott V, Tessema S, Greenhouse B, Erlank E, Koekemoer LL, Sturrock HJW, Mwilima A, Katokele S, Uusiku P, Bennett A, Smith JL, Kleinschmidt I, Mumbengegwi D, Gosling R. Effectiveness of reactive focal mass drug administration and reactive focal vector control to reduce malaria transmission in the low malaria-endemic setting of Namibia: a cluster-randomised controlled, open-label, two-by-two factorial design trial. Lancet. 2020 Apr 25;395(10233):1361-1373. doi: 10.1016/S0140-6736(20)30470-0. — View Citation
Llanos-Cuentas A, Lacerda MVG, Hien TT, Velez ID, Namaik-Larp C, Chu CS, Villegas MF, Val F, Monteiro WM, Brito MAM, Costa MRF, Chuquiyauri R, Casapia M, Nguyen CH, Aruachan S, Papwijitsil R, Nosten FH, Bancone G, Angus B, Duparc S, Craig G, Rousell VM, Jones SW, Hardaker E, Clover DD, Kendall L, Mohamed K, Koh GCKW, Wilches VM, Breton JJ, Green JA. Tafenoquine versus Primaquine to Prevent Relapse of Plasmodium vivax Malaria. N Engl J Med. 2019 Jan 17;380(3):229-241. doi: 10.1056/NEJMoa1802537. — View Citation
Ntuku H, Smith-Gueye C, Scott V, Njau J, Whittemore B, Zelman B, Tambo M, Prach LM, Wu L, Schrubbe L, Kang Dufour MS, Mwilima A, Uusiku P, Sturrock H, Bennett A, Smith J, Kleinschmidt I, Mumbengegwi D, Gosling R, Hsiang M. Cost and cost effectiveness of reactive case detection (RACD), reactive focal mass drug administration (rfMDA) and reactive focal vector control (RAVC) to reduce malaria in the low endemic setting of Namibia: an analysis alongside a 2x2 factorial design cluster randomised controlled trial. BMJ Open. 2022 Jun 23;12(6):e049050. doi: 10.1136/bmjopen-2021-049050. — View Citation
PAHO. Fourth Meeting of the Malaria Technical Advisory Group (TAG) to the Pan American Health Organization (PAHO). Washington D.C.: Pan American Health Organization, World Health Organization, Americas. https://www.paho.org/hq/index.php?option=com_docman&view=download&alias=50391-fourthmalaria-technical-advisory-group-meeting-report-may-washington-dc&category_slug=malariatechnical-advisory-group&Itemid=270&lang=en; 2019.
World Health Organization (WHO). WHO Guidelines for malaria. 3 June 2022. https://reliefweb.int/report/world/who-guidelines-malaria-3-june-2022#:~:text=The%20WHO%20global%20malaria%20strategy,residual%20foci%20of%20malaria%20transmission.
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Cumulative Incidence of Plasmodium vivax infections | Number of microscopy-confirmed, Plasmodium vivax malaria cases in residents reported from health facilities per population over the 36-month follow-up study period | From enrollment through study completion, over 36-month follow-up study period | |
Secondary | Prevalence of Plasmodium vivax infection | Proportion of individuals with polymerase chain reaction (PCR)-confirmed infection in an endline survey | At endline survey in trial year 4, 3 years after enrollment in study in trial year 1 | |
Secondary | Plasmodium vivax seroprevalence | Proportion of participants who are seropositive, rate at which seronegative individuals became seropositive estimated from age-specific seroprevalence from endline survey, adjusted by modeling longitudinal individual serological status and/or antibody titers | At endline survey in trial year 4, 3 years after enrollment in study in trial year 1 | |
Secondary | Genetic diversity of Plasmodium vivax | Diversity of locally acquired infections as defined by sequencing results | From enrollment through study completion, over 4 trial years | |
Secondary | Tolerability of study drugs | Vomiting following administration of study drugs and non-adherence related to adverse effects | Over drug administration period, unique for each study drug (7 days for CQ/PQ regimens and 3 days for CQ/TQ regimens) | |
Secondary | Adherence to study drugs | Number of missed doses | Unique for each patient based on drug regimen (7 days for CQ/PQ regimens and 3 days for CQ/TQ regimens) | |
Secondary | Refusal rates | Number of refusals divided by number of individuals invited to participate | During each fMDA round, twice per year for 3 consecutive years | |
Secondary | Program costs per unit fMDA round | Total costs divided by number of fMDA rounds | From enrollment through study completion, over 4 years | |
Secondary | Program costs per unit | Total costs divided by number of individuals receiving intervention | From enrollment through study completion, over 4 years | |
Secondary | Cost per incident case averted | Difference in cost between fMDA and control divided by the difference in the effect (incidence) | From enrollment through study completion, over 4 years | |
Secondary | Cost per disability life year (DALY) | Difference in cost between fMDA and control divided by the difference in the effect (DALYs) | From enrollment through study completion, over 4 years | |
Secondary | Cost per economic dollar due to malaria saved | Difference in cost between fMDA and control divided by the difference in the effect (economic dollar due to malaria) | From enrollment through study completion, over 4 years |
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