CHILD Malaria: Child Health and Infection With Low Density (CHILD) Malaria

• Sponsor: University of California, San Francisco (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05567016
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID) (NIH), Ifakara Health Institute (Other), Swiss Tropical & Public Health Institute (Other), Stanford University (Other), Chan Zuckerberg Biohub (Other)
• Enrollment: 600
• Location: 1
• Arms: 3
• Anticipated Duration (Months): 47
• Patients Per Site Per Month: 12.8

Study Details

Study Description

Brief Summary

This trial will assess the long-term health and socioeconomic impact of interventions targeting low-density malaria infection (LMI) among children in Tanzania

Condition or Disease	Intervention/Treatment	Phase
Malaria,Falciparum; Malaria	Drug: Artemether-lumefantrine; Drug: Artemether-lumefantrine; Drug: Artemether-lumefantrine	Phase 3

Detailed Description

This is a 3-arm open-label randomized control trial of 600 children aged 6 months to 10 years in Tanzania, where transmission is low and a high proportion of infections are low-density. Standard of care based on passive case detection (PCD) using rapid diagnostic test (control arm) will be compared to two different approaches to detect and treat P. falciparum LMI: active case detection using molecular testing (ACDm) and PCD using molecular testing (PCDm).

Aims are:

1. To assess the impact of standard PCD plus ACDm vs standard PCD on long-term child health

2. To assess the impact of PCDm vs standard PCD on long-term child health

3. To evaluate the cost-effectiveness of ACDm and PCDm

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 600 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Individual randomized controlled trialIndividual randomized controlled trial
• Masking: None (Open Label)
• Masking Description: This will be an open label RCT. Participants and personnel administering the intervention will be unblinded. Assessment of the primary outcome will be unblinded. Assessment of several secondary outcomes will be blinded as feasible.
• Primary Purpose: Treatment
• Official Title: Child Health and Infection With Low Density (CHILD) Malaria, a Randomized Controlled Trial to Assess the Long-term Health and Socioeconomic Impact of Interventions Targeting Low-density Malaria Infection (LMI) Among Children in Tanzania
• Anticipated Study Start Date: Apr 1, 2023
• Anticipated Primary Completion Date: May 1, 2025
• Anticipated Study Completion Date: Mar 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active Case Detection using molecular testing (ACDm) Per standard of care, children will receive passive case detection (PCD) using rapid diagnostic test (RDT). Children will receive malaria active case detection (ACD) using RDT and qPCR three times yearly with treatment using artemether-lumefantrine (AL) if RDT or qPCR positive.	Drug: Artemether-lumefantrine; AL will be administered if malaria infection is detected by ACDm; Drug: Artemether-lumefantrine; AL will be administered if malaria infection is detected by RDT or microscopy in standard PCD
Experimental: Passive Case Detection using molecular testing (PCDm) Children who present with fever will receive PCD using RDT and qPCR with treatment using AL if RDT or qPCR positive. Per standard of care, children will not receive malaria ACD.	Drug: Artemether-lumefantrine; AL will be administered if malaria infection is detected by PCDm; Drug: Artemether-lumefantrine; AL will be administered if malaria infection is detected by RDT or microscopy in standard PCD
Active Comparator: Standard passive case detection (PCD) Per standard of care, children will receive PCD using RDT. Per standard of care, children will not receive malaria ACD.	Drug: Artemether-lumefantrine; AL will be administered if malaria infection is detected by RDT or microscopy in standard PCD

Outcome Measures

Primary Outcome Measures

1. Incidence of all-cause sick visits [24 months from enrollment]

   Number of sick visits to health facility per person time

Secondary Outcome Measures

1. Prevalence of anemia [24 months from enrollment]

   Proportion of routine Hb measurements that are low (<11 g/dL) or moderate-severe low (<8 g/dL)

2. Incidence of underweight status [24 months from enrollment]

   Incidence of underweight status will be defined as the percentage of participants with low weight for age z-scores of less than -2. The World Health Organization (WHO) anthropometric indices will be utilized for standards.

3. Incidence of stunting [24 months from enrollment]

   Incidence of stunting will be defined as the percentage of participants with low height for age z-scores of less than -2. The World Health Organization (WHO) anthropometric indices will be utilized for standards.

4. Incidence of wasting [24 months from enrollment]

   Incidence of wasting will be defined as the percentage of participants with low weight for height z-scores of less than -2. The World Health Organization (WHO) anthropometric indices will be utilized for standards.

5. Incidence of malnutrition [24 months from enrollment]

   Incidence of malnutrition will be defined as the percentage of participants with a z-score of -3 to -2 indicating moderate malnutrition or a z-score of less than -3 indicating severe malnutrition in any of the following: weight for age, height for age, or weight for height.

6. Tolerability of study drugs [24 months from enrollment]

   Vomiting following administration of study drugs

7. All-cause fever episodes [24 months from enrollment]

   Incidence of all-cause fever episodes

8. Incidence of clinical symptoms [24 months from enrollment]

   Number of days with overall symptoms reported as moderate (≥3 on a 5-point scale) per person time

9. Incidence of clinical malaria [24 months from enrollment]

   New episodes of positive malaria test (with fever or other clinical symptoms) per person time

10. Proportion of fever episodes with clinical failure [24 months from enrollment]

    Proportion of fever episodes that lead to clinical failure, defined as persistent or worsening symptoms assessed 7 and 28 days after initial evaluation.

11. Prevalence of parasitemia [24 months from enrollment]

    Proportion of routine samples with parasites detected by microscopy or qPCR.

12. Incidence in antibiotics prescribed [24 months from enrollment]

    Number of antibiotic regimens prescribed per person time

13. Cognitive ability among children 0-2.9 years of age on the Global Scales of Early Development (GSED) [24 months from enrollment]

    The GSED is a validated instrument which combines caregiver report and direct assessment to measure holistic development across multiple domains (cognitive, motor, language, social-emotional). Scores are continuous developmental D-scores which will be standardized by age to create a Development-for-Age-Z-score.

14. Cognitive ability among children 3-5 years of age on the International Development and Early Learning Assessment (IDELA) [24 months from enrollment]

    The IDELA is a validated, global tool that uses direct child assessment to measure early learning and development across 4 core domains (Emergent Literacy, Emergent Numeracy, Motor, Social-emotional). Scores range from 0-100% as a percentage of correct tasks averaged across the 4 domains.

15. Cognitive ability among children 6-12 years of age on the Kaufman Assessment Battery for Children (KABC) [24 months from enrollment]

    The KABC is an individually administered, culturally fair test that measures cognitive abilities in children. There are 18 subtests that assess knowledge, memory, pattern recognition, serial reasoning, and more.

16. Sustained attention among children 6-12 years of age on the Test of Everyday Attention for Children (TEA-ch) [24 months from enrollment]

    The TEA-ch is a valid and reliable battery of tests for the assessment of attention in children. The tool uses gamelike tests to assess different forms of attention including selective, sustained, divided, and attentional switching as well as dual task performance.

17. Incidence of school absenteeism [24 months from enrollment]

    The number of days of school absenteeism for any reason including illness.

18. School performance [24 months from enrollment]

    School performance will be defined as the incidence of school advancement to the next grade.

19. Socioeconomic costs to participant [24 months from enrollment]

    Estimated long-term income loss due to impaired early childhood development

20. Socioeconomic costs to family [24 months from enrollment]

    Total caregiver-reported costs of sick visits and transport to sick visits plus estimated loss of income from number of days of caregiver work absenteeism.

21. Socioeconomic costs to health system [24 months from enrollment]

    Estimated costs of testing and treatment for caregiver-reported number of sick visits.

22. Cost effectiveness [24 months from enrollment]

    Cost per outcome averted (e.g., per sick visit averted, per disability adjusted life years (DALYs), and per economic dollar saved, etc.)

23. Prevalence of systemic inflammation [24 months from enrollment]

    Proportion of visits with elevated inflammatory markers

24. Proportion with antimalarial immune responses [24 months from enrollment]

    Percentage of patients with antimalarial antibodies

25. Proportion with biomarkers of inflammation [24 months from enrollment]

    Percentage of patients with elevated cytokines

26. Proportion with general antibody responses to vaccines [24 months from enrollment]

    Percentage of patients with vaccine antibodies

27. Proportion with general antibody responses to common pathogens [24 months from enrollment]

    Percentage of patients with common pathogen antibodies

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Months to 10 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. 6 months to 10 years of age

2. Residence in the study area

3. Agree to come to study clinic for any illness

4. Agree to avoid medications outside the study

Exclusion Criteria:

1. Another child from household already randomly selected for recruitment

2. Not able or refusal to provide informed consent

3. Need for emergency intervention

4. Antimalarial use within the last 28 days

5. Known history of chronic illness including diabetes mellitus, cancer, or stage 3 or 4 HIV/AIDS (per WHO criteria)

6. Contraindications to artemether-lumefantrine (AL) including history of allergic reaction, weight under 5 kg

7. Participation in another active/ongoing intervention trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kiwangwa and Fukayosi clinics	Bagamoyo		Tanzania

Sponsors and Collaborators

• University of California, San Francisco
• National Institute of Allergy and Infectious Diseases (NIAID)
• Ifakara Health Institute
• Swiss Tropical & Public Health Institute
• Stanford University
• Chan Zuckerberg Biohub

Investigators

• Principal Investigator: Michelle Hsiang, MD, MSc, University of California, San Francisco
• Principal Investigator: Ally Olotu, MD, PhD, Ifakara Health Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT05567016
• Other Study ID Numbers: DMID protocol 21-0046; U01AI155315
• First Posted: Oct 5, 2022
• Last Update Posted: Oct 5, 2022
• Last Verified: Sep 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by University of California, San Francisco: malaria; child health; chronic infection; subclinical infection; patent infection; subpatent infection; active case detection; passive case detection; fever case management
• Additional relevant MeSH terms: Infections; Malaria; Malaria, Falciparum; Lumefantrine; Artemether; Artemether, Lumefantrine Drug Combination

Study Results

No Results Posted as of Oct 5, 2022