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Evaluation of Reactive Focal Mass Drug Administration (rfMDA) in Namibia

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ClinicalTrials.gov Identifier: NCT02610400
Recruitment Status : Completed
First Posted : November 20, 2015
Last Update Posted : January 4, 2019
Sponsor:
Collaborators:
University of Texas
London School of Hygiene and Tropical Medicine
University of Southampton
The Novartis Foundation
Clinton Health Access Initiative, Nigeria
Information provided by (Responsible Party):
University of California, San Francisco

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.

Condition or disease Intervention/treatment Phase
Malaria Combination Product: RACD Combination Product: RAVC Combination Product: rfMDA Phase 3

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9845 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Targeted Parasite Elimination in the Human and Mosquito to Reduce Malaria Transmission: A Cluster Randomised Controlled Factorial Design Trial of Reactive Focal Drug Administration (rfMDA) Versus Reactive Case Detection (RACD), With and Without Reactive Vector Control (RAVC), From the Low Endemic Setting of Namibia
Study Start Date : February 2016
Actual Primary Completion Date : December 2017
Actual Study Completion Date : December 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
Experimental: RACD without RAVC
In this arm, subjects will receive RACD without the addition of RAVC.
Combination Product: RACD

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

Other Name: Reactive Case Detection

Experimental: RACD+RAVC

In this arm, subjects will receive both:

(i) reactive case detection (RACD) and (ii) additional reactive vector control (RAVC)

Combination Product: RACD

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

Other Name: Reactive Case Detection

Combination Product: RAVC
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.
Other Name: Reactive Vector Control

Experimental: rfMDA without RAVC
In this arm, subjects will receive reactive focal mass drug administration (rfMDA) without the addition of RAVC.
Combination Product: RAVC
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.
Other Name: Reactive Vector Control

Combination Product: rfMDA

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

Other Name: Reactive focal mass drug administration

Experimental: rfMDA+RAVC

In this arm, subjects will receive both:

(i) reactive focal mass drug administration (rfMDA) and (ii) RAVC.

Combination Product: rfMDA

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

Other Name: Reactive focal mass drug administration




Primary Outcome Measures :
  1. Incidence [ Time Frame: Up to 24 months ]
    Incidence of confirmed, passively identified malaria cases


Secondary Outcome Measures :
  1. All-age infection prevalence [ Time Frame: Up to 24 months ]
    The investigators will determine all-age infection prevalence using loop-mediated isothermal amplification (LAMP) during the cross-sectional household survey. This survey will be administered to a sample of residents of all intervention Enumeration Areas in the Study Area at study conclusion.

  2. All-age seroprevalence [ Time Frame: Up to 24 months ]
    The investigators will determine all-age seroprevalence using ELISA during the cross-sectional household survey. This survey will be administered to a sample of residents of all intervention EAs in the Study Area at study conclusion.

  3. Feasibility of attaining coverage [ Time Frame: Up to 24 months ]
    The investigators will compare coverage of each intervention package and determine the feasibility of reaching 80% coverage for each intervention package. For RACD intervention, this equates to the proportion of the population living in the Target Area that receives a finger prick to test for malaria. For TPE intervention, coverage equates to the proportion that receive an initial dose of antimalarial drug (intention to treat analysis). For RAVC intervention, coverage is defined as the proportion of houses in the Target Area that receive reactive Indoor Residual Spraying (IRS).

  4. Safety: Serious adverse events (SAEs) [ Time Frame: Up to 24 months ]
    The investigators will compare the count of serious adverse events (SAEs) relative to the total number of participants receiving an Intervention, across interventions.

  5. Acceptability [ Time Frame: Up to 24 months ]
    Using focus group discussions (FGDs), the investigators will ask two questions: "Was this intervention acceptable to [participant]?" and "Would [participant] participate in this intervention again if given the opportunity?". The investigators will compare the % of "yes" responses to each of these questions, in the TPE versus the RACD arms.

  6. Refusal rates [ Time Frame: Up to 24 months ]
    Refusal rates for each intervention

  7. Cost of intervention [ Time Frame: Up to 24 months ]
    The investigators will collect detailed expenditure data on costs of delivery of the TPE and RACD interventions. Calculations will include costs for all consumables, as well as staff time, which will be prospectively collected every 10th TPE or RACD event. The investigators will compare TPE versus RACD in terms of cost per intervention event as well as cost per population intervened upon.

  8. Medication adherence [ Time Frame: Up to 24 months ]
    The investigators will measure medication adherence in both TPE and RACD by scheduled pill counts in a random subset of subjects receiving each of those interventions.



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Months and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Index Case Investigation Inclusion Criteria:

    • 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
  2. RACD Intervention Inclusion Criteria:

    • 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.
  3. rfMDA Intervention Inclusion Criteria:

    • 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.
  4. Artemether/Lumefantrine (A-L) (combination medication) Inclusion Criteria:

    • Consent to take A-L medication
    • Does not meet A-L Exclusion Criteria under item #4 below
  5. Pill count Inclusion Criteria:

    • Provides consent, and
    • People who receive any number of RACD or rfMDA drug dose(s)
  6. Reactive Vector Control Inclusion Criteria:

    • 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
  7. Endline Survey, Individual, Inclusion Criteria:

    • Provides informed consent, and
    • Resides or spent at least 1 night in the EA in the preceding 4 weeks
  8. Acceptability Assessment: Individual Interviews with study participants, Inclusion Criteria:

    • Provides informed consent, and
    • Resident of index household or of neighbouring households
  9. Acceptability Assessment: Individual Interviews with key stakeholders, Inclusion Criteria:

    • In leadership position within Zambezi region, and
    • Provides informed consent
  10. Acceptability Assessment: Individual Interview with refusers, Inclusion Criteria:

    • Refused to participate in rfMDA, RACD, and/or RAVC, and
    • Provides informed consent to take part in the anonymous survey
  11. Acceptability Assessment: Focus group discussions with study participants, Inclusion Criteria:

    • Provides informed consent, and
    • Was eligible to be enrolled in the study in participant's Target Area, and
    • Either took part in RACD or rfMDA intervention (+/- RAVC), OR refused these interventions

Exclusion Criteria:

  1. Index Case Investigation Exclusion Criteria:

    • Malaria infection identified through active case detection
    • Refusal to participate
  2. RACD Intervention Exclusion Criteria:

    • Index case does not reside in study EA, or
    • Refusal to participate in RACD, or
    • Household received the intervention in the previous 5 weeks, or
    • Household > 500 m from the index case, or
    • Severe or complicated malaria as assessed by study nurse (this will lead to referral for further evaluation at health facility but not enrolment in study)
  3. rfMDA Intervention Exclusion Criteria:

    • Index case does not reside in study EA, or
    • Refusal to participate in rfMDA, or
    • Household received the intervention in the previous 5 weeks, or
    • Household > 500 m from the index case, or
    • Severe or complicated malaria as assessed by study nurse (this will lead to referral for further evaluation at health facility but not enrolment in study)
  4. Artemether/Lumefantrine (combination medication) Exclusion Criteria:

    • Pregnancy in first trimester, or
    • Previous regular menstruation, with no menstruation for most recent 4 weeks, or
    • Weight < 5 kg*, or
    • Severe malaria, or
    • Known allergy to A-L, or
    • Refusal of the offered A-L

      • Note regarding A-L weight exclusion: Because of the pre-set required field at the top of the Eligibility section of this Application, the investigators have indicated a 6 month minimum age limit, primarily to note to the reader that there will be a lower age limit to infants enrolled. Yet during the actual conduct of this trial the investigators will utilize 5 kg weight as the cutoff, rather than using age. A lower weight cutoff of 5 kg is in accordance with A-L's manufacturer (Novartis)'s guidance on supporting pediatric data.
  5. Pill count Exclusion Criteria:

    • Refusal to participate in pill count, or
    • Individuals who did not receive any drug doses through RACD or rfMDA
  6. Reactive Vector Control Exclusion Criteria:

    • Refusal by head of household to participate in RAVC, or
    • Already received RAVC during current transmission season, or
    • Household is > 500 m from index case household (note: refusal to participate in RACD or rfMDA is not an exclusion criterion for RAVC)
  7. Endline Survey, Individual, Exclusion Criteria:

    • Refusal to participate in Endline Survey (note: lack of participation in rfMDA or RACD is not an exclusion criterion)

  8. Acceptability Assessment: Individual Interviews with study participants, Exclusion Criteria:

    • Refusal to participate in Acceptability Assessment, or
    • Speaks language not understood or able to be translated, or
    • Key stakeholder [see below]
    • Age < 15 years
  9. Acceptability Assessment: Individual Interviews with key stakeholders, Exclusion Criteria:

    • Refusal to participate in Acceptability Assessment, or
    • Speaks language not understood or able to be translated, or
    • Not in leadership position
  10. Acceptability Assessment: Individual Interview with refusers, Exclusion Criteria:

    • Refusal to participate in Acceptability Assessment, or
    • Speaks language not understood or able to be translated, or
    • Age < 15 years
  11. Acceptability Assessment: Focus group discussions with study participants, Exclusion Criteria:

    • Refusal to participate in Acceptability Assessment, or
    • Speaks language not understood or able to be translated, or
    • Key stakeholder or in another leadership position, or
    • Age < 15 years

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02610400


Locations
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Namibia
University of Namibia Multidisciplinary Research Centre
Windhoek, Namibia
Sponsors and Collaborators
University of California, San Francisco
University of Texas
London School of Hygiene and Tropical Medicine
University of Southampton
The Novartis Foundation
Clinton Health Access Initiative, Nigeria
Investigators
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Principal Investigator: Michelle Hsiang, MD University of California, San Francisco
  Study Documents (Full-Text)

Documents provided by University of California, San Francisco:

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT02610400     History of Changes
Other Study ID Numbers: OPP1089413_Namibia_rfMDA
First Posted: November 20, 2015    Key Record Dates
Last Update Posted: January 4, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Additional relevant MeSH terms:
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Malaria
Protozoan Infections
Parasitic Diseases