Evaluation of Reactive Focal Mass Drug Administration (rfMDA) +/- Reactive Focal Vector Control (RAVC) in Namibia

NCT02610400 | Completed Phase 3 DMC

• 1 other identifier: OPP1089413_Namibia_rfMDA
• Study Type: interventional
• Target: 9,845
• Locations: 1 country
• Sites: 1

Brief Summary

This is a cluster randomised controlled trial with factorial study design comparing the impact of reactive community-based malaria interventions: 1) presumptive treatment (or rfMDA, reactive focal mass drug administration) versus reactive case detection (RACD), and 2) reactive IRS (indoor residual spraying) versus control on the incidence of malaria in Namibia.

Conditions

Malaria

Outcome Measures

Primary Outcomes (1)

• Incidence

  Incidence of confirmed, passively identified malaria cases

  Up to 12 months

Secondary Outcomes (8)

• All-age infection prevalence

  Up to 12 months

• All-age seroprevalence

  Up to 12 months

• Feasibility of attaining coverage

  Up to 12 months

• Safety: Serious adverse events (SAEs)

  Up to 12 months

• Acceptability

  Up to 12 months

Study Arms (4)

RACD without RAVC

EXPERIMENTAL

In this arm, subjects will receive RACD without the addition of RAVC.

Combination Product: RACD

RACD+RAVC

EXPERIMENTAL

In this arm, subjects will receive both: (i) reactive case detection (RACD) and (ii) additional reactive vector control (RAVC)

Combination Product: RACD; Combination Product: RAVC

rfMDA without RAVC

EXPERIMENTAL

In this arm, subjects will receive reactive focal mass drug administration (rfMDA) without the addition of RAVC.

Combination Product: RAVC; Combination Product: rfMDA

rfMDA+RAVC

EXPERIMENTAL

In this arm, subjects will receive both: (i) reactive focal mass drug administration (rfMDA) and (ii) RAVC.

Combination Product: rfMDA

Interventions

RACD COMBINATION_PRODUCT

Active malaria surveillance using rapid diagnostic test in households around passively-detected index case. RDT-positive subjects are treated per national policy, under which combination medication artemether-lumefantrine is first-line, using dosing (mg artemether / mg lumefantrine): (i) 5-14kg patient: 20/120mg twice (8 hr apart) on day 1, 20/120mg twice (12 hr apart) on each of days 2 and 3 then stop (ii) 15-24kg patient: 40/240mg twice (8 hrs apart) on day 1, 40/240mg twice (12 hrs apart) on each of days 2 and 3 then stop (iii) 25-34kg patient: 60/360mg twice (8 hrs apart) on day 1, 60/360mg twice (12 hrs apart) on each of days 2 and 3 then stop (iv) \> 34kg patient: 80/480mg twice (8 hrs apart) on day 1, 80/480mg twice (12 hrs apart) on each of days 2 and 3, then stop

Also known as: Reactive Case Detection

RACD without RAVC; RACD+RAVC

RAVC COMBINATION_PRODUCT

Focal, targeted indoor spraying with long-lasting insecticide pirimiphos-methyl or Actellic 300 CS, a World Health Organization (WHO)-approved organophosphate. Safety measures: (i) seeking advance permission to spray; (ii) temporarily removing items (utensils, water, food, pets) from the building during spray; (iii) covering all unremovable items; (iv) asking inhabitants to temporarily relocate outdoors during spray; (v) advising children remain outdoors until floors washed; and (vi) avoiding of spraying of any rooms that contain inhabitants, animals, or incorrectly removed/covered items. Actellic will be applied according to National Vector-borne Disease Control Program (NVDCP) indoor residual spraying (IRS) guidelines, using a Hudson X-pert sprayer (Hudson Manufacturing Co., Chicago, USA) at 40 mL/m-sq.

Also known as: Reactive Vector Control

RACD+RAVC; rfMDA without RAVC

rfMDA COMBINATION_PRODUCT

Presumptive treatment, using the medication A-L, of the inhabitants of households surrounding a passively-detected index case, without incorporating a diagnostic test step. The investigators will administer A-L with dosing as follows (mg artemether / mg lumefantrine): (i) 5-14kg patient: 20/120mg twice (8 hours apart) on day 1, 20/120mg twice (12 hours apart) on each of days 2 and 3, then stop (ii) 15-24kg patient: 40/240mg twice (8 hours apart) on day 1, 40/240mg twice (12 hours apart) on each of days 2 and 3, then stop (iii) 25-34kg patient: 60/360mg twice (8 hours apart) on day 1, 60/360mg twice (12 hours apart) on each of days 2 and 3, then stop (iv) \> 34kg patient: 80/480mg twice (8 hours apart) on day 1, 80/480mg twice (12 hours apart) on each of days 2 and 3, then stop

Also known as: Reactive focal mass drug administration

rfMDA without RAVC; rfMDA+RAVC

Eligibility Criteria

• Age: 6 Months+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Malaria infection (either locally transmitted or imported) detected at a health facility via passive surveillance, and
• Resides in a study Enumeration Area (EA), and
• Provides informed consent
• Provides informed consent, and
• Index case resides in study EA, and
• All non-index cases that reside or spent at least one night in the Target Area in the past 4 weeks, and
• Residents of the six houses closest to the index case, and
• If 25 people are not enrolled in the study at the first six houses, plus the index case household, after the second visit then additional houses can be approached on the third visit.
• Provides informed consent, and
• Index case resides in study EA, and
• All non-index cases that reside or spent at least one night in the Target Area in the past 4 weeks, and
• Residents of the six houses closest to the index case, and
• If 25 people are not enrolled in the study at the first six houses, plus the index case household, after the second visit then additional houses can be approached on the third visit.
• Consent to take A-L medication

You may not qualify if:

• Provides consent, and
• People who receive any number of RACD or rfMDA drug dose(s)
• Informed consent provided by head of household or person in otherwise in charge of household, and
• Index case resides in study EA, and
• Index household and 6 non-index households closest to index household
• Provides informed consent, and
• Resides or spent at least 1 night in the EA in the preceding 4 weeks
• Provides informed consent, and
• Resident of index household or of neighbouring households
• In leadership position within Zambezi region, and
• Provides informed consent
• Refused to participate in rfMDA, RACD, and/or RAVC, and
• Provides informed consent to take part in the anonymous survey
• Provides informed consent, and
• Was eligible to be enrolled in the study in participant's Target Area, and

Sponsors & Collaborators

• University of California, San Francisco: lead
• University of Texas: collaborator
• London School of Hygiene and Tropical Medicine: collaborator
• University of Southampton: collaborator
• The Novartis Foundation: collaborator
• Clinton Health Access Initiative, Nigeria: collaborator

Study Sites (1)

University of Namibia Multidisciplinary Research Centre

Windhoek, Namibia

Location

Related Publications (13)

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• Hsiang MS, Hwang J, Kunene S, Drakeley C, Kandula D, Novotny J, Parizo J, Jensen T, Tong M, Kemere J, Dlamini S, Moonen B, Angov E, Dutta S, Ockenhouse C, Dorsey G, Greenhouse B. Surveillance for malaria elimination in Swaziland: a national cross-sectional study using pooled PCR and serology. PLoS One. 2012;7(1):e29550. doi: 10.1371/journal.pone.0029550. Epub 2012 Jan 6.

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• Oxborough RM, Kitau J, Jones R, Feston E, Matowo J, Mosha FW, Rowland MW. Long-lasting control of Anopheles arabiensis by a single spray application of micro-encapsulated pirimiphos-methyl (Actellic(R) 300 CS). Malar J. 2014 Jan 29;13:37. doi: 10.1186/1475-2875-13-37.

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• White NJ. Intermittent presumptive treatment for malaria. PLoS Med. 2005 Jan;2(1):e3. doi: 10.1371/journal.pmed.0020003.

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• Katrak S, Gasasira A, Arinaitwe E, Kakuru A, Wanzira H, Bigira V, Sandison TG, Homsy J, Tappero JW, Kamya MR, Dorsey G. Safety and tolerability of artemether-lumefantrine versus dihydroartemisinin-piperaquine for malaria in young HIV-infected and uninfected children. Malar J. 2009 Nov 30;8:272. doi: 10.1186/1475-2875-8-272.

  PMID: 19948038 BACKGROUND

• Banek K, Lalani M, Staedke SG, Chandramohan D. Adherence to artemisinin-based combination therapy for the treatment of malaria: a systematic review of the evidence. Malar J. 2014 Jan 6;13:7. doi: 10.1186/1475-2875-13-7.

  PMID: 24386988 BACKGROUND

• 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.

  PMID: 35738650 DERIVED

• 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.

  PMID: 32334702 DERIVED

• Medzihradsky OF, Kleinschmidt I, Mumbengegwi D, Roberts KW, McCreesh P, Dufour MK, Uusiku P, Katokele S, Bennett A, Smith J, Sturrock H, Prach LM, Ntuku H, Tambo M, Didier B, Greenhouse B, Gani Z, Aerts A, Gosling R, Hsiang MS. Study protocol for a cluster randomised controlled factorial design trial to assess the effectiveness and feasibility of reactive focal mass drug administration and vector control to reduce malaria transmission in the low endemic setting of Namibia. BMJ Open. 2018 Jan 27;8(1):e019294. doi: 10.1136/bmjopen-2017-019294.

  PMID: 29374672 DERIVED

MeSH Terms

Conditions

Malaria

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Michelle Hsiang, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2015
• First Posted: November 20, 2015
• Study Start: February 1, 2016
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: July 17, 2020

Record last verified: 2020-07

Locations

NA (1)