- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04182126
HS#2017-3512, Adaptive Interventions for Optimizing Malaria Control: A Cluster-Randomized SMART Trial
Environmental Modifications in Sub-Saharan Africa: Changing Epidemiology, Transmission and Pathogenesis of Plasmodium Falciparum and P. Vivax Malaria
Study Overview
Status
Conditions
Detailed Description
In the past decade, massive scale-up of long-lasting insecticide-treated nets (LLINs) and indoor residual spraying (IRS) in Africa have led to significant reductions in malaria mortality and mobility. However, current first-line interventions are not sufficient to eliminate malaria in most countries. The widespread use of pyrethroid insecticides has resulted in resistant vector populations, and high coverage of LLINs and IRS has led to increased outdoor human feeding behavior and resting behavior. These changes in vector ecology and behaviors have significantly limited the effectiveness of current first-line interventions that target indoor biting and resting mosquitoes. Furthermore, as a result of ecological changes and intervention measures, malaria risk in a locality is dynamic, and the utility of malaria intervention tools may vary as new tools are being approved and introduced and the cost of each tool differs among locations and over time. Such variations in malaria risk, vector ecology, and utility of intervention tools exemplify the need to develop optimal adaptive interventions tailored to local malaria risks, vector ecology and supply chains. The central objective of this application is to design optimal adaptive combinations of vector control interventions to maximize reductions in malaria burden based on local malaria transmission risks, changing vector ecology, and available mix of interventions approved by the Ministry of Health in each target country. The central hypothesis is that an adaptive approach based on local malaria risk and changing vector ecology will lead to significant reductions in malaria incidence and transmission risk. To accomplish this objective, we propose the following three specific aims:
- Measure malaria incidence and predict risk using environmental, biological, social, and climatic features with machine learning approaches. Hypothesis: Malaria risk prediction can be improved through the use of machine learning techniques that include environmental, biological, socio-economic, and climatic features. Approach: Each site will measure malaria incidence, prevalence and social economic factors through community surveys. Classification-based and regression-based approaches will be used to develop malaria risk predictive models, and model performance will be validated. Outcome: This Aim will establish improved malaria risk prediction models and lay an important foundation for developing intervention strategies adaptive to local vector ecology and future malaria risks using reinforced machine learning approaches.
- Use a cluster-randomized sequential, multiple assignment randomized trial (SMART) design to develop an optimal adaptive intervention strategy. Hypothesis: Malaria control interventions that are adapted to local malaria risk and vector ecology and are cost effective can be identified using a cluster-randomized SMART design. Approach: Cluster-randomized SMART design will be used in a high transmission areas in Kenya to evaluate the impact of adaptive interventions that involve sequential and combinational use of next-generation nets, indoor spraying of non-pyrethroid insecticides, and larval source management for malaria control.
- Evaluate the cost-effectiveness and impact of an adaptive intervention approach on secondary endpoints related to malaria risk and transmission. Hypothesis: Intervention strategies adapted to local malaria risk and vector ecology will be more cost-effective in reducing malaria incidence and transmission risk than the currently-used LLIN intervention. Approach: The economic costs of individual interventions or combinations thereof will be assessed from both a provider and societal perspective using standard economic evaluation methodologies. Cost-effectiveness will be measured in terms of cost per person protected. The study will examine changes in drug and insecticide resistance and infection prevalence attributable to the adaptive interventions.
Malaria interventions adapted to rapidly changing malaria risk and vector ecologies are critically needed to improve the effectiveness of malaria control measures. This study will use new techniques, including machine learning and a novel cluster-randomized SMART design, to develop optimal adaptive malaria intervention strategies.
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Guiyun Yan, Ph.D.
- Phone Number: 19498240175
- Email: guiyuny@uci.edu
Study Contact Backup
- Name: Guiyun Yan
- Phone Number: 19498240175
- Email: guiyuny@uci.edu
Study Locations
-
-
Homa Bay County
-
Homa Bay, Homa Bay County, Kenya
- Recruiting
- Tom-Mboya University College, Maseno University
-
Contact:
- Harrysone E Atieli, Ph.D.
- Phone Number: +254 721 347 437
- Email: etemesi2012@yahoo.com
-
Contact:
- John Githure, Ph.D.
- Email: jgithure@gmail.com
-
Sub-Investigator:
- Andrew K Githeko, Ph.D.
-
Sub-Investigator:
- Gordon Okomo, Ph.D.
-
-
-
-
California
-
Irvine, California, United States, 92697
- Active, not recruiting
- Program in Public Health
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Household inclusion criteria:
- Households with residents at the time of survey
- Agreement of the adult resident to provide informed consent for the intervention and survey
Study subjects inclusion criteria:
- Passive case detection by health facilities will include all residents in the study clusters; active case detection will include residents of >6 months
- Agreement of parent/guardian to provide informed consent and minors to provide assent.
Household exclusion criteria:
- Household vacant
- No adult resident home on more than 3 occasions
Study subjects exclusion criteria:
• Participants not home on day of survey
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Sequential Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Regular long-lasting insecticidal nets
All participants will have LLIN coverage through routine MoH distribution of long-lasting insecticidal nets (LLINs), no other interventions will be applied.
Regular LLIN: Olyset nets containing 2% permethrin or PermaNet 2.0 containing 1.8 and 1.4 g/kg, respectively, for 75 and 100 denier yarn.
|
Olyset nets: containing 2% permethrin or PermaNet 2.0 containing 1.8 and 1.4 g/kg, respectively, for 75 and 100 denier yarn
Other Names:
|
Experimental: Piperonyl butoxide-treated LLIN
All participants will received piperonyl butoxide-treated LLINs (PBO-LLINs) at Stage 1 and Stage 2 interventions provided that PBO-LLINs are effective at Stage 1 interventions. Each household will be provided on PBO-LLIN per two people with appropriate eduction. PBO-LLIN: Olyset Plus, containing 2% permethrin and 1% PBO. |
Olyset Plus: containing 2% permethrin and 1% PBO
Other Names:
|
Experimental: PBO-LLIN plus larval source management
All participants will received piperonyl butoxide-treated LLINs (PBO-LLINs) at Stage 1, however, Stage 1 intervention is not effective.
All participants will received PBO-LLINs plus larval source management (LSM) at Stage 2. LSM will be implemented in selected clusters, including both physical and chemical methods by physical filling or removal of temporary larval habitats and larviciding of semi-permanent and permanent habitats, per the National Malaria Strategic Plan of Kenya.
We will use the long-lasting microbial larvicides manufactured by Central Life Sciences.
Semi-permanent and permanent habitats will be treated with FourStar® 180-day Briquets using the recommended dosage of 100 ft2 water surface per briquet.
|
Olyset Plus: containing 2% permethrin and 1% PBO
Other Names:
Semi-permanent and permanent habitats will be treated with FourStar® 180-day Briquets using the recommended dosage of 100 ft2 water surface per briquet
Other Names:
|
Experimental: PBO-LLIN plus enhanced methods
All participants will received piperonyl butoxide-treated LLINs (PBO-LLINs) at Stage 1, however, Stage 1 intervention is not effective.
All participants will received PBO-LLINs plus an enhanced intervention at Stage 2. The enhanced intervention is determined by machine learning method.
|
Olyset Plus: containing 2% permethrin and 1% PBO
Other Names:
|
Experimental: LLIN plus indoor residual spraying
All participants will received regular LLINs plus indoor residual spraying (IRS) (LLIN+IRS) at Stage 1 and Stage 2 interventions provided that LLIN+IRS is effective at Stage 1 interventions.
For LLIN+IRS clusters, each dwelling's interior walls and ceilings will be sprayed with micro-encapsulated pirimiphos-methyl (Actellic 300CS) at the recommended dosage of 1g/m² and at the recommended frequency of once a year.
|
Olyset nets: containing 2% permethrin or PermaNet 2.0 containing 1.8 and 1.4 g/kg, respectively, for 75 and 100 denier yarn
Other Names:
each dwelling's interior walls and ceilings will be sprayed with micro-encapsulated pirimiphos-methyl at the recommended dosage of 1g/m² and at the recommended frequency of once a year
Other Names:
|
Experimental: LLIN+IRS+LSM
All participants will received regular LLINs plus IRS at Stage 1, provided that LLIN+IRS is not effective.
LSM will be added on these clusters at Stage 2 interventions.
LSM at Stage 2 will be the long-lasting microbial larvicides manufactured by Central Life Sciences.
Semi-permanent and permanent habitats will be treated with FourStar® 180-day Briquets using the recommended dosage of 100 ft2 water surface per briquet.
|
Olyset nets: containing 2% permethrin or PermaNet 2.0 containing 1.8 and 1.4 g/kg, respectively, for 75 and 100 denier yarn
Other Names:
Semi-permanent and permanent habitats will be treated with FourStar® 180-day Briquets using the recommended dosage of 100 ft2 water surface per briquet
Other Names:
each dwelling's interior walls and ceilings will be sprayed with micro-encapsulated pirimiphos-methyl at the recommended dosage of 1g/m² and at the recommended frequency of once a year
Other Names:
|
Experimental: LLIN+IRS plus enhanced method
All participants will received regular LLINs plus IRS at Stage 1, provided that LLIN+IRS is not effective.
Enhanced method will be added on these clusters at Stage 2 interventions.The enhanced intervention is determined by machine learning method.
|
Olyset nets: containing 2% permethrin or PermaNet 2.0 containing 1.8 and 1.4 g/kg, respectively, for 75 and 100 denier yarn
Other Names:
each dwelling's interior walls and ceilings will be sprayed with micro-encapsulated pirimiphos-methyl at the recommended dosage of 1g/m² and at the recommended frequency of once a year
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Annual clinical malaria incidence rate
Time Frame: Clinical malaria will be monitored for up to 60 months
|
To compare clinical malaria incidence rates among different intervention arms
|
Clinical malaria will be monitored for up to 60 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Malaria infection prevalence
Time Frame: Infection prevalence will be monitored for up to 60 months
|
To compare infection prevalence rates among different intervention arms using microscopic, RDT and molecular diagnostic methods
|
Infection prevalence will be monitored for up to 60 months
|
Malaria vector density
Time Frame: Vector density will be monitored for up to 60 months
|
To compare malaria vector densities between different intervention arms
|
Vector density will be monitored for up to 60 months
|
Malaria transmission intensity
Time Frame: Entomological inoculation rate will be examined for up to 60 months
|
To compare entomological inoculation rates between different intervention arms
|
Entomological inoculation rate will be examined for up to 60 months
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: John Githure, Ph.D., Tom-Mboya University, Kenya
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- U19AI129326-03S1 (U.S. NIH Grant/Contract)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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