Optimization of Seasonal Malaria Chemoprevention (SMC) Delivery (SMC)

April 30, 2018 updated by: Alassane Dicko, University of Bamako

Optimal Delivery of Seasonal Malaria Chemoprevention and Its Effects on the Acquisition of Malaria Immunity

Based in part on the pivotal studies conducted in Mali, SMC was approved by WHO as a policy for malaria control in countries with seasonal malaria transmission such as Mali in March 2012. The goals are to identify the most effective method to deliver SMC, and to obtain more information on the long term impact of SMC on malaria immunity. Our specific aims are 1) to determine the optimal mode (fixed-point (FPD) vs door-to-door delivery (DDD); directly observed treatment (DOT) vs non-DOT (NDOT)) and frequency (3 vs 4 doses per season) of SMC delivery; 2) to compare quantitative measures of immunity in children who do and do not receive SMC. A cluster-randomized design will be sued. The target population will be children aged 3-59 months old in Ouelessebougou district, Mali. In Year 1, villages in four sub-districts will be randomized into four groups (FPD+DOT; FPD+NDOT; DDD+DOT; DDD+NDOT). The optimal mode of delivery will be selected based on the SMC coverage during the first year, and will then be implemented in villages of two additional sub-districts. Villages in these two newly selected sub-districts will be randomized in two groups. Children in the first group will received three rounds of SMC and those in the second group will receive four rounds of SMC to determine the optimal frequency of SMC based on the incidence rate of clinical malaria as measured by passive surveillance. In Year 3, children in the selected sub-districts will received SMC by the optimal delivery system determined in Years 1 -2. A survey will be conducted collect data on mortality and hospital admission and compare these outcomes in areas where SMC was implemented and areas where SMC was not implemented.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Based in part on the pivotal studies conducted in Mali, SMC was approved by WHO as a policy for malaria control in countries with seasonal malaria transmission such as Mali in March 2012. The strategy is a highly cost-effective approach to reduce childhood mortality in these areas. Despite the huge benefit of the SMC on malaria infection and disease, the optimal approach to deliver SMC remains to be determined and there is no data on the long term effect of this strategy on the development of immunity to malaria. While fixed-point delivery (FPD) combined with non directly observed treatment (NDOT) by community health workers is attractive for the SMC implementation, it is need to be evaluated and compared to other mode of delivery. The objectives are to identify the most effective method to deliver SMC, and to obtain information on the long term impact of SMC on malaria immunity. Specifically, i) to determine the optimal mode (fixed-point (FPD) vs door-to-door delivery (DDD); directly observed treatment (DOT) vs. non-DOT (NDOT)) and frequency (3 vs. 4 doses per season) of SMC delivery; ii) to compare quantitative measures of immunity in children who do and do not receive SMC over a three year period.

The design is a cluster-randomized trial over three years. The target population is children aged 3-59 months old living in Ouelessebougou district, Mali. In Year 1, villages in four sub-districts will be randomized into four groups (FPD+DOT; FPD+NDOT; DDD+DOT; DDD+NDOT). The optimal mode of delivery will be selected based on the SMC coverage during the first year, and will then be implemented in villages of two additional sub-districts. Villages in these two newly selected sub-districts will be randomized in two groups. Children in the first group will received three rounds of SMC and those in the second group will receive four rounds of SMC to determine the optimal frequency of SMC based on the incidence rate of clinical malaria as measured by passive surveillance. Children in the four sub-districts selected in Year 1 will continue to receive three rounds of SMC in Year 2 using the optimal mode of delivery. In Year 3, children in the randomly selected sub-districts will received SMC by the optimal delivery system determined in Years 1 -2. Immune responses will be measured and compared between the children receiving SMC to a cohort of children not receiving SMC, to assess the impact of SMC on key antimalarial antibody responses over the three year period using cross-sectional surveys at the beginning and the end of the transmission season.

In Year 3, 4 and 5 surveys will be conducted to collect data on mortality and hospital admissions and compare these outcomes in areas where SMC was implemented and areas where SMC was not implemented.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
10000

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Mali
      • Bamako, Mali
        • Recruiting
        • Malaria Research and Training Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

3 months to 4 years (Child)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

Age >= 3 months & < 60 months

Exclusion Criteria:

  • severe, chronic illness
  • known allergy to one of the study drugs (SP or AQ)
  • known HIV positive subjects using Cotrimoxazole.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: FPD+NDOT
Fixed-point delivery (FPD) combined with non directly observed treatment (NDOT)
Other: FPD+NDOT
Other Names:
  • fixed-point delivery + non directly observed treatment
Other: FPD+DOT
Fixed-point delivery (FPD) combined with directly observed treatment (DOT)
Other: FPD+DOT
Other Names:
  • fixed-point delivery + directly observed treatment
Other: DDD+NDOT
door-to-door delivery (DDD) combined with non directly observed treatment (NDOT)
Other: DDD+NDOT
Door to door delivery + non directly observed treatment
Other: DDD+DOT
door-to-door delivery (DDD) combined with directly observed treatment (NDOT)
Other: DDD+DOT
Door to door delivery + directly observed treatment

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Coverage of SMC
Time Frame: 1-5 weeks after last round of SMC in Year1
SMC coverage will be defined as proportion of the children who have received the three treatments doses at each of the three rounds of SMC.
1-5 weeks after last round of SMC in Year1
Incidence of clinical malaria in Year 2
Time Frame: up to 4 weeks after the last round of SMC
Clinical malaria defined as signs and symptoms suggestive of malaria with positive RDT and/or positive blood smear.
up to 4 weeks after the last round of SMC
Mortality rate
Time Frame: 1, 2, 3, 4 years of the intervention
death
1, 2, 3, 4 years of the intervention
Hospital admission
Time Frame: 1, 2, 3, 4 years of the intervention
Hospitalization
1, 2, 3, 4 years of the intervention

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
malaria parasitemia
Time Frame: one week before the first round of SMC and 4-6 weeks after the last round of SMC
Parasite prevalence defined as the proportion of children with a positive malaria blood smear and parasite density
one week before the first round of SMC and 4-6 weeks after the last round of SMC
moderate anemia
Time Frame: one week before the first round of SMC and 4-6 weeks after the last round of SMC
Prevalence of moderate anemia defined as hemoglobin concentration < 8 g/dL measured by hemoglobin analyzer
one week before the first round of SMC and 4-6 weeks after the last round of SMC
immune response to malaria parasite
Time Frame: one week before the first round of SMC and 4-6 weeks after the last round of SMC
Cellular and humoral antimalarial immune responses to malaria parasites
one week before the first round of SMC and 4-6 weeks after the last round of SMC
molecular markers of resistance to SP + AQ
Time Frame: one week before the first round of SMC and 4-6 weeks after the last round of SMC
Frequency of mutations at codons 51, 59, and 108 of the dhfr gene, 437 and 540 of the dhps gene, codon 76 in the P. falciparum chloroquine transporter gene (pfcrt), and codon 86 of the P. falciparum multidrug resistance gene one (pfmdr1).
one week before the first round of SMC and 4-6 weeks after the last round of SMC
nutritional status
Time Frame: one week before the first round of SMC and 4-6 weeks after the last round of SMC
Prevalence of wasting stunting and underweight as defined by WHO Global database on Child Growth and Malnutrition
one week before the first round of SMC and 4-6 weeks after the last round of SMC
Clinical malaria in Year 1
Time Frame: up to 4 weeks after the last round of SMC
Clinical malaria defined as signs and symptoms suggestive of malaria with positive RDT and/or positive blood smear.
up to 4 weeks after the last round of SMC

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Bamako

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2014

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2018

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 29, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 31, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 5, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 2, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 30, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2014-61

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.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings