Evaluation of Targeted Mass Drug Administration for Malaria in Ethiopia

NCT ID: NCT04241705

Last Updated: 2020-06-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

48960 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-01-20

Study Completion Date

2022-01-20

Brief Summary

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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.

Detailed Description

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Study design: Cluster randomized controlled trial

Primary aim: To compare the effect of targeted mass drug administration (tMDA) versus reactive case detection (RCD) on reducing malaria incidence

Study site: Elimination targeted areas within East Hararghe Zones, Oromia Regional State, which is comprised of 24 woredas/districts

Cluster or unit of randomization: Kebeles will be randomized to the control, RCD or tMDA arms using simple randomization

Evaluation methods: The primary outcome measure of annual parasite incidence (API) will be obtained through routine surveillance data at all health facilities (health centers and health posts).

Secondary outcomes will be measured through cross-sectional surveys and study monitoring data:

1. Case investigation. At the time of diagnosis of the index case and enrollment of community members to the study, a short questionnaire will be administered to collect demographic data and assess malaria risk, including past malaria treatment and travel history, access to malaria interventions, occupation, etc.
2. Cross-sectional surveys. At baseline and end of the study period (year 2), cross-sectional household surveys will be conducted to assess malaria prevalence, household and individual risk factors for malaria, including access to malaria interventions. It will also assess knowledge of, attitude towards, and participation in the study intervention.
3. Longitudinal feasibility measurements: Coverage of RCD or tMDA in the target population, acceptability of RCD or tMDA in the target population, serious adverse event (SAE) reports, adherence measured by self-report and pill count, and cost data from all arms
4. Laboratory testing: The conventional rapid diagnostic test (RDT) for malaria will be used in the RCD arm. Dried blood spots (DBS) will be collected for molecular and serological testing during the cross-sectional surveys in all arms. DBS collected in incident cases as part of routine surveillance as well as during the RCD activities will also be utilized for antigen, antibody, and molecular testing. G6PD testing will be used in the RCD and tMDA arm to guide primaquine (PQ) treatment.

Sample size: To measure the primary outcome, change in incidence, 16,000 Households (HH) (16 clusters, 1,000 HH each) per arm will be included in the study. For the cross-sectional surveys, 320 randomly selected HHs per arm (16 clusters, 20HH/cluster) will be included.

Conditions

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Malaria

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Control arm

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.

Group Type ACTIVE_COMPARATOR

Optimized malaria control interventions

Intervention Type OTHER

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.

Reactive Case Detection (RCD) arm

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.

Group Type ACTIVE_COMPARATOR

Treatment of positive individuals per national treatment guidelines

Intervention Type OTHER

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)

Optimized malaria control interventions

Intervention Type OTHER

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.

Targeted Mass Drug Administration (tMDA) arm

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.

Group Type EXPERIMENTAL

Presumptive treatment with artemether-lumefantrine (AL) plus 14 days of primaquine (PQ)

Intervention Type OTHER

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.

Optimized malaria control interventions

Intervention Type OTHER

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.

Interventions

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Treatment of positive individuals per national treatment guidelines

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)

Intervention Type OTHER

Presumptive treatment with artemether-lumefantrine (AL) plus 14 days of primaquine (PQ)

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.

Intervention Type OTHER

Optimized malaria control interventions

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.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* 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:

Exclusion Criteria

* 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
Minimum Eligible Age

6 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Addis Continental Institute of Public Health

OTHER

Sponsor Role collaborator

U.S. President's Malaria Initiative

UNKNOWN

Sponsor Role collaborator

U.S. Centers for Disease Control and Prevention

UNKNOWN

Sponsor Role collaborator

United States Agency for International Development (USAID)

FED

Sponsor Role collaborator

Ethiopian Federal Ministry of Health

UNKNOWN

Sponsor Role collaborator

Oromia Regional Health Bureau

UNKNOWN

Sponsor Role collaborator

Tulane University

OTHER

Sponsor Role collaborator

Armauer Hansen Research Institute, Ethiopia

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Endalamaw Gadisa, PhD, MSc

Role: PRINCIPAL_INVESTIGATOR

AHRI Ethiopia

Locations

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Woreda 1:

Babīlē, , Ethiopia

Site Status RECRUITING

Woreda 2:

Fedīs, , Ethiopia

Site Status RECRUITING

Woreda 3:

Girawa, , Ethiopia

Site Status RECRUITING

Woreda 4:

Golo Oda, , Ethiopia

Site Status RECRUITING

Woreda 5:

Gursum, , Ethiopia

Site Status RECRUITING

Woreda 7:

Kersa, , Ethiopia

Site Status RECRUITING

Woreda 8:

Kombolcha, , Ethiopia

Site Status RECRUITING

Woreda 9:

Kurfa Chele, , Ethiopia

Site Status RECRUITING

Woreda 10:

Midega Tola, , Ethiopia

Site Status RECRUITING

Woreda 6:

‘Alemaya, , Ethiopia

Site Status RECRUITING

Countries

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Ethiopia

Central Contacts

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Endalamaw Gadisa, PhD, MSc

Role: CONTACT

+251911868827

Ayele Zewdie, MD, MPH

Role: CONTACT

+251911764018

References

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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.

Reference Type DERIVED
PMID: 35392979 (View on PubMed)

Provided Documents

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Document Type: Informed Consent Form

View Document

Other Identifiers

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1

Identifier Type: -

Identifier Source: org_study_id

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