Clinical trial NCT04241705: Evaluation of Targeted Mass Drug Administration for Malaria in Ethiopia
Official title: Evaluation of the Effect of Targeted Mass Drug Administration and Reactive Case Detection on Malaria Transmission and Elimination in East Hararghe Zone, Oromia, Ethiopia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Malaria
Keywords: Targeted mass drug administration
Reactive case detection
Lead sponsor: Armauer Hansen Research Institute, Ethiopia
Sponsor class: OTHER
Collaborators: name: Addis Continental Institute of Public Health
name: U.S. President's Malaria Initiative
name: U.S. Centers for Disease Control and Prevention
name: United States Agency for International Development (USAID)
name: Ethiopian Federal Ministry of Health
name: Oromia Regional Health Bureau
name: Tulane University
First posted: 2020-01-27
Enrollment: 48960
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Detailed description: 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.

Eligibility criteria: 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:

  * All residents of the intervention study kebeles diagnosed with malaria at health facilities (index case) or reside within 100-meter radius with the index case and has NONE of the exclusion criteria listed below
  * Able to provide informed written consent

Exclusion Criteria:

* 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

Primary outcomes:
measure: Change in malaria annual parasite incidence (API)
timeFrame: Two years
Secondary outcomes:
measure: Malaria burden, measured by antigen test
timeFrame: Two years
measure: Malaria burden, measured by serology
timeFrame: Two years
measure: Malaria burden, measured by molecular testing
timeFrame: Two years
measure: Intervention coverage
timeFrame: Two years
measure: Acceptability
timeFrame: Two years
measure: Serious adverse events
timeFrame: Two years
measure: Adherence
timeFrame: Two years
measure: Costs
timeFrame: Two years
measure: Cost-effectiveness
timeFrame: Two years
measure: Sensitivity and specificity of polymerase chain reaction (PCR)
timeFrame: Two years
measure: Ratio of imported to locally acquired incident cases
timeFrame: Two years
Other outcomes:
Locations:
city: Alemaya
country: Ethiopia
facility: Woreda 6:
city: Babile
country: Ethiopia
facility: Woreda 1:
city: Fedis
country: Ethiopia
facility: Woreda 2:
city: Girawa
country: Ethiopia
facility: Woreda 3:
city: Golo oda
country: Ethiopia
facility: Woreda 4:
city: Gursum
country: Ethiopia
facility: Woreda 5:
city: Kersa
country: Ethiopia
facility: Woreda 7:
city: Kombolcha
country: Ethiopia
facility: Woreda 8:
city: Kurfa chele
country: Ethiopia
facility: Woreda 9:
city: Midega Tola
country: Ethiopia
facility: Woreda 10:
Study officials:
affiliation: AHRI Ethiopia
name: Endalamaw Gadisa, PhD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.