NCT04241705

Brief Summary

Reactive and proactive case detection measures are widely implemented by national malaria elimination programs globally. Similarly, the Ethiopian Federal Ministry of Health decided to include reactive case detection (RCD) and targeted mass drug administration (tMDA) approaches as part of their elimination strategy, along with rigorous evaluation. This study aims to evaluate the impact on annual parasite incidence (API) and cost-effectiveness of implementing tMDA and RCD within a 100-meter radius of passively detected index case, compared with standard of care in the control arm. In addition, cross-sectional surveys will measure the change in malaria prevalence over the two-year study intervention period. The aim is to generate evidence to inform Ethiopia's national strategy for malaria elimination.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
48,960

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Jan 2020

Typical duration for not_applicable

Geographic Reach
1 country

10 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 2, 2020

Completed
18 days until next milestone

Study Start

First participant enrolled

January 20, 2020

Completed
7 days until next milestone

First Posted

Study publicly available on registry

January 27, 2020

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 20, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 20, 2022

Completed
Last Updated

June 12, 2020

Status Verified

June 1, 2020

Enrollment Period

2 years

First QC Date

January 2, 2020

Last Update Submit

June 11, 2020

Conditions

Keywords

Targeted mass drug administrationReactive case detection

Outcome Measures

Primary Outcomes (1)

  • Change in malaria annual parasite incidence (API)

    The effect of RCD or tMDA will be defined as a change in malaria API among residents measured by microscopy/RDT through health centers and health posts. The malaria API will be defined as all passively detected RDT or microscopy confirmed cases over a period of 12 months, who are residents of the kebele divided by the estimated population in the intervention kebele multiplied by 1000. The primary effectiveness endpoint will therefore be API among residents of the kebele at baseline and year 2 of each intervention group of study clusters, compared with the control clusters.

    Two years

Secondary Outcomes (11)

  • Malaria burden, measured by antigen test

    Two years

  • Malaria burden, measured by serology

    Two years

  • Malaria burden, measured by molecular testing

    Two years

  • Intervention coverage

    Two years

  • Acceptability

    Two years

  • +6 more secondary outcomes

Study Arms (3)

Control arm

ACTIVE COMPARATOR

The control arm will provide optimized malaria control interventions that includes strengthened surveillance systems and commodities management, scale-up of vector control and case management services.

Other: Optimized malaria control interventions

Reactive Case Detection (RCD) arm

ACTIVE COMPARATOR

Optimized malaria control interventions as in the control arm. In addition, following identification of microscopy or RDT positive, passively-detected index cases at the health post or health center; individuals who reside within a 100-meter radius of the index case will receive diagnosis for malaria using a conventional RDT. Positive individuals will receive treatment and follow-up as per the national treatment guidelines. 14 days of primaquine (PQ) will only be administered to those found to be normal upon G6PD testing. Additional procedures will include the collection of a dried blood spot.

Other: Treatment of positive individuals per national treatment guidelinesOther: Optimized malaria control interventions

Targeted Mass Drug Administration (tMDA) arm

EXPERIMENTAL

Optimized malaria control interventions as in the control arm. In addition, following identification of microscopy or RDT positive index cases at the health post or health center, all eligible individuals who reside within a 100-meter radius of the index case will receive presumptive treatment with artemether-lumefantrine (AL) plus 14 days of primaquine (PQ) (0.25mg/kg daily). 14 days of primaquine (PQ) will only be administered to those found to be normal upon G6PD testing.

Other: Presumptive treatment with artemether-lumefantrine (AL) plus 14 days of primaquine (PQ)Other: Optimized malaria control interventions

Interventions

Treatment for everyone except children \<6 months of age, pregnant women, women breastfeeding children \<6 months of age, and women 12-49 years of age with an unknown pregnancy status: * P. falciparum cases: artemether-lumefantrine (AL) plus single dose primaquine (PQ) (0.25mg/kg daily) * P. vivax cases: chloroquine (CQ) plus 14 days of PQ (0.25mg/kg daily) * Mixed infections: AL plus 14 days of PQ (0.25mg/kg daily) Treatment for pregnant women and women breastfeeding children \<6 months of age: * P. falciparum cases or mixed infections: Quinine (1st trimester); AL (2nd \& 3rd trimesters or breastfeeding) * P. vivax cases: Chloroquine (CQ)

Reactive Case Detection (RCD) arm

Everyone who is eligible for the study except pregnant women and women breastfeeding children \<6 months of age AND who are confirmed to have normal G6PD status will be treated presumptively with artemether-lumefantrine (AL) plus 14 days of primaquine (PQ). Treatment will be given without RDT for malaria. * Women in the first trimester of pregnancy will be treated presumptively with quinine. * Women in the second and third trimesters or women who are breastfeeding will receive artemether-lumefantrine (AL). Again, treatment will be given without RDT for malaria.

Targeted Mass Drug Administration (tMDA) arm

Optimized malaria control interventions that includes strengthened surveillance systems and commodities management, scale-up of vector control and case management services including follow-up, and social and behavior change communication to seek prompt treatment and use long lasting insecticidal nets (LLINs). Case management includes passive detection of malaria cases and treatment with artemether-lumefantrine (AL) plus single low dose primaquine (PQ) (0.25mg/kg once) for Plasmodium falciparum (Pf) cases and chloroquine (CQ) plus 14 days of PQ (0.25mg/kg daily) for Plasmodium vivax (Pv) cases, and AL plus 14 days of PQ (0.25mg/kg daily) for mixed infections as well as follow-up at the health post or health center on days 3, 7, and 13 for those receiving 14 days of PQ to assess for adverse events and adherence as per the national treatment guidelines.

Control armReactive Case Detection (RCD) armTargeted Mass Drug Administration (tMDA) arm

Eligibility Criteria

Age6 Months+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Woreda-level: Of the 19 woredas with malaria risk, the ten woredas with the highest annual parasite incidence (API) in 2018 will be eligible for the study.
  • For Kebeles:
  • Kebeles in East Hararghe Zone targeted for implementation of elimination activities by the Ethiopian Federal Ministry of Health where there is ongoing PMI-supported malaria surveillance;
  • Kebeles with reported API between 1 and 50;
  • Kebeles in malarious districts with comparable optimization of malaria control interventions.
  • For individual participants:

You may not qualify if:

  • Able to provide informed written consent
  • For kebeles: Kebeles planning on starting for the first time or discontinuing indoor residual spraying (IRS) campaigns in the next two years.
  • For individual participants:
  • Children less than 6 months of age or \<5 kg
  • Known allergy or history of adverse reaction or chronic/congenital disease contra indicated to any of the intervention drugs: PQ, AL or CQ
  • Individuals with severe malnutrition or signs of severe disease, with evidence of any organ failure or Hgb level \< 8gm/dl
  • Household members already covered by the intervention less or equal to one month before
  • In addition, the following individuals will be excluded from receiving primaquine:
  • Phenotypically G6PD deficient individuals
  • Pregnant women
  • Lactating women breastfeeding infants less than 6 months of age or with unknown G6PD status

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

Woreda 1:

Babīlē, Ethiopia

RECRUITING

Woreda 2:

Fedīs, Ethiopia

RECRUITING

Woreda 3:

Girawa, Ethiopia

RECRUITING

Woreda 4:

Golo Oda, Ethiopia

RECRUITING

Woreda 5:

Gursum, Ethiopia

RECRUITING

Woreda 7:

Kersa, Ethiopia

RECRUITING

Woreda 8:

Kombolcha, Ethiopia

RECRUITING

Woreda 9:

Kurfa Chele, Ethiopia

RECRUITING

Woreda 10:

Midega Tola, Ethiopia

RECRUITING

Woreda 6:

‘Alemaya, Ethiopia

RECRUITING

Related Publications (1)

  • Abdelmenan S, Teka H, Hwang J, Girma S, Chibsa S, Tongren E, Murphy M, Haile M, Dillu D, Kassim J, Behaksra S, Tadesse FG, Yukich J, Berhane Y, Worku A, Keating J, Zewde A, Gadisa E. Evaluation of the effect of targeted Mass Drug Administration and Reactive Case Detection on malaria transmission and elimination in Eastern Hararghe zone, Oromia, Ethiopia: a cluster randomized control trial. Trials. 2022 Apr 7;23(1):267. doi: 10.1186/s13063-022-06199-8.

MeSH Terms

Conditions

Malaria

Interventions

Artemether, Lumefantrine Drug CombinationPrimaquine

Condition Hierarchy (Ancestors)

Protozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne Diseases

Intervention Hierarchy (Ancestors)

ArtemetherArtemisininsReactive Oxygen SpeciesFree RadicalsInorganic ChemicalsOrganic ChemicalsLumefantrineFluorenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsSesquiterpenesTerpenesPolycyclic CompoundsDrug CombinationsPharmaceutical PreparationsAminoquinolinesQuinolinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Endalamaw Gadisa, PhD, MSc

    AHRI Ethiopia

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Endalamaw Gadisa, PhD, MSc

CONTACT

Ayele Zewdie, MD, MPH

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 2, 2020

First Posted

January 27, 2020

Study Start

January 20, 2020

Primary Completion

January 20, 2022

Study Completion

January 20, 2022

Last Updated

June 12, 2020

Record last verified: 2020-06

Data Sharing

IPD Sharing
Will not share

Locations