Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202311470737025 Date of Approval: 06/11/2023
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title CHILD (Child Health and Infection with Low Density) Malaria
Official scientific 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
Brief summary describing the background and objectives of the trial As malaria declines, low-density malaria infections (LMI) represent an increasing proportion of infections and may have negative impacts on health and cognition in children, necessitating development of targeted and effective solutions. This trial will assess the health, cognitive, and socioeconomic impact of two strategies for detecting and treating LMI in a low transmission setting.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Malaria
Purpose of the trial Prevention
Anticipated trial start date 05/06/2023
Actual trial start date 18/07/2023
Anticipated date of last follow up 14/11/2025
Actual Last follow-up date
Anticipated target sample size (number of participants) 600
Actual target sample size (number of participants)
Recruitment status Active, not recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
NCT05567016 Clinicaltrials.gov
210046 NIH Division of Microbiology and Infectious Diseases Protocol number
U01AI155315 NIH Grant Award number
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Passive Case Detection 24 months The control arm is the standard of care in Tanzania. When participants are ill and present to the health facility with fever they will receive passive malaria detection using rapid diagnostics test (RDT), and those found to be RDT-positive treated with artemether-lumefantrine. 200 Active-Treatment of Control Group
Experimental Group Active case detection with molecular testing 24 months When participants visit the health facility with fever, they will receive the standard of care, which includes passive case detection of malaria by rapid diagnostics tests (RDT) and treatment with artemether-lumefantrine of RDT-positive individuals. Additionally, three times per year, all participants in this group will receive active case detection with molecular testing. During these visits, all participants will be get an RDT malaria test. Those who test negative by RDT will get an additional malaria test by quantitative PCR (qPCR). RDT or qPCR positive participants with uncomplicated malaria will be treated with artemether-lumefantrine. Two rounds of ACDm will be conducted during the two high transmission season peaks (approximately June/July, then Oct/Nov) and one ACDm round at the end of the high transmission season (approximately Feb). 200
Experimental Group Passive Case Detection with Molecular Testing 24 months When study participants in this study arm are ill, they will receive care through the local study health facility, which will include passive case detection of malaria using rapid diagnostic test (RDT) for fever and treatment with artemether-lumefantrine if RDT-positive. If they are RDT-negative, a second malaria test by quantitative PCR will be conducted, and qPCR-positive participants treated with artemether-lumefantrine. 200
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. 6 months to 10 years. 2. Primary residence in the study area during the study period. 3. Agree to come to study clinic for any illness. 4. Agree to avoid medications outside of study, even herbal medication. 1. Another child from household already randomly selected for recruitment. 2. Not able or does not provide informed consent. 3. Need for emergency intervention. 4. Known history of chronic illness requiring regular specialty care including diabetes mellitus, cancer, or Stage 3 or 4 HIV/AIDS. 5. Contraindications to artemether-lumefantrine including history of allergic reaction, weight under 5 kg. 6. Participation in another active/on-going intervention trial. Child: 6 Year-12 Year,Infant: 0 Month(s)-12 Month(s),Infant: 13 Month(s)-24 Month(s),Preschool Child: 2 Year-5 Year 6 Month(s) 10 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 27/01/2023 IFAKARA HEALTH INSTITUTE Institutional Review Board
Ethics Committee Address
Street address City Postal code Country
Plot 463, Kiko Avenue, Mikocheni Dar es Salaam 14112 United Republic of Tanzania
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 29/03/2022 University of California San Francisco Institutional Review Board
Ethics Committee Address
Street address City Postal code Country
490 Illinois Street, Floor 6 San Francisco CA 94143 United States of America
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 30/01/2023 Tanzania National Institute of Medical Research
Ethics Committee Address
Street address City Postal code Country
3 Barack Obama Drive Dar es Salaam 11101 United Republic of Tanzania
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Cumulative incidence of all cause sick visits define as the number of sick visits to health facility excluding planned admissions for medical care, elective surgery, and trauma per person-time. Monthly for 24 months, and at sick visits and days 7 and 28 post-sick visit follow-up
Secondary Outcome Prevalence of anemia defined as the proportion of routine Hb measurements that are low (<11 g/dL) or moderate-severe low (<8 g/dL) At enrollment and months 2, 6,8, 12, 14, 18, 20, 24 from enrollment.
Secondary Outcome Prevalence of parasitaemia defined as proportion of routine samples with parasites detected by microscopy or qPCR At enrollment and monthly for 24 months, and at sick visits and day 28 post-sick visit follow-up
Secondary Outcome Prevalence 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. At enrollment and months 2, 4, 6, 8, 10, 12,14,16,18,20,22,24 from enrollment, and at sick visits
Secondary Outcome Prevalence 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. At enrollment and months 2, 4, 6, 8, 10, 12,14,16,18,20,22,24 from enrollment, and at sick visits
Secondary Outcome Prevalence 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. At enrollment and months 2, 4, 6, 8, 10, 12,14,16,18,20,22,24 from enrollment, and at sick visits
Secondary Outcome Prevalence 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. At enrollment and months 2, 4, 6, 8, 10, 12,14,16,18,20,22,24 from enrollment, and at sick visits
Secondary Outcome Prevalence of vomiting following administration of study drugs defined as vomiting immediately or within 30minutes following administration of study drugs and measures of non-adherence Monthly for 24 months from enrollment
Secondary Outcome All-cause fever episodes defined as the number of documented fever episodes (axillary temperature of ≥37.5°C) per person time and number of fever episodes (documented and reported) per person time Monthly for 24 months, and at sick visits and days 7 and 28 post-sick visit follow-up
Secondary Outcome Incidence of clinical symptoms defined as number of days with overall symptoms reported as moderate (≥3 on a 5-point scale) per person time At enrollment and monthly for 24 months, and at sick visits and day 7 and 28 post-sick visit follow-up
Secondary Outcome Incidence of clinical malaria defined as new episodes of positive malaria test (with fever or other clinical symptoms) per person time At enrollment and monthly for 24 months, and at sick visits and day 28 post-sick visit follow-up
Secondary Outcome Proportion of fever episodes with clinical failure defined as proportion of fever episodes that lead to clinical failure, defined as persistent or worsening symptoms assessed 7 and 28 days after initial evaluation. Monthly for 24 months, and at sick visits and days 7 and 28 post-sick visit follow-up
Secondary Outcome Incidence in antibiotics prescribed defined as number of antibiotic regimens prescribed per person time Monthly for 24 months, and at sick visits and days 7 and 28 post-sick visit follow-up
Secondary Outcome Cognitive ability among children 0-3.4 years of age on the Global Scales of Early Development (GSED) At enrollment and month 24 from enrollment
Secondary Outcome Cognitive ability among children 3.5-5 years of age on the International Development and Early Learning Assessment (IDELA) At enrollment and month 24 from enrollment
Secondary Outcome Cognitive ability among children 6-12 years of age on the East Africa Neurodevelopment Assessment Tool At enrollment and month 24 from enrollment
Secondary Outcome Sustained attention among children 5-8 years of age on the Pencil Tapping Test At enrollment and month 24 from enrollment
Secondary Outcome Sustained attention among children 9-12 years of age on the Code Transmission Test, a local adaptation of the Test of Everyday Attention for Children(TEA-Ch) At enrollment and month 24 from enrollment
Secondary Outcome Incidence of school absenteeism defined as the number of days of school absenteeism for any reason including illness. Monthly for 24 months, and at sick visits and days 7 and 28 post-sick visit follow-up
Secondary Outcome School performance will be defined as the incidence of school advancement to the next grade. At months 6,12,18, and 24 from enrollment
Secondary Outcome Socioeconomic costs to participant defined as the estimated long-term income loss due to impaired early childhood development Monthly for 24 months from enrollment, and at sick visits and days 7 and 28 post-sick visit follow-ups
Secondary Outcome Socioeconomic costs to health system defined as estimated costs of testing and treatment for caregiver-reported number of sick visits. Monthly for 24 months from enrollment, and at sick visits and days 7 and 28 post-sick visit follow-ups
Secondary Outcome Cost effectiveness defined as cost per outcome averted (e.g., per sick visit averted, per disability adjusted life years (DALYs), and per economic dollar saved, etc.) At enrollment and for 24 months from enrollment
Secondary Outcome Prevalence of systemic inflammation defined as proportion of sick visits with elevated elevated C-reactive pep-tide (CRP) At sick visits and D28 post-sick visit follow-up
Secondary Outcome Proportion with antimalarial antibodies against P.falciparum defined as percentage of patients with antimalarial antibodies At enrollment and months 2,4,6,8,10,12,14,16,18,20,22,24 from enrollment, and at sick visits and day 28 post-sick visit follow-up
Secondary Outcome Proportion with biomarkers of inflammation defined as percentage of patients with elevated cytokines At enrollment and at months 6, 12, 18, 24 from enrollment, at at D28 post-sick visit follow-up
Secondary Outcome Proportion with general antibody responses to vaccines defined as percentage of patients with vaccine antibodies At enrollment and at months 6, 12, 18, 24 from enrollment, at at D28 post-sick visit follow-up
Secondary Outcome Proportion with general antibody responses to common pathogens defined as percentage of patients with common pathogen antibodies At enrollment and at months 6, 12, 18, 24 from enrollment, at at D28 post-sick visit follow-up
Secondary Outcome Incidence of adverse events (AEs) defined as number of AEs per person time. AEs will be considered as any grade 3-4 AE or serious adverse event (SAE); individual AEs; or AEs related to study drugs. Monthly for 1-24 months from enrollment, and at days 7 and 28 post-sick visit follow-up
Secondary Outcome Incidence of wasting. Incidence proportion of wasting will be defined for each age range of measurement. It is defined as the proportion of children not wasted at the start of the period who became wasted during the age period (the proportion of children who had the onset of new episodes during the period). Incident wasting episodes are defined as a change in weight-for-length z-scores from above -2 Z in the prior measurement to below -2 Z in the current measurement. We will define incident severe wasting analogously using a -3 Z cutoff. We will assume a 60-day washout period before a new wasting episode could occur. At enrollment and months 2, 4, 6, 8, 10, 12,14,16,18,20,22,24 from enrollment, and at sick visits
Secondary Outcome Incidence of stunting. Incidence proportion of stunting will be defined for each age range of measurement. It is defined as the proportion of children not stunted at the start of the period who became stunted during the age period. Incident stunting episodes will be defined as a change in length-for-age z-scores from above -2 Z in the prior measurement to below -2 Z in the current measurement. We will define incident severe stunting analogously using a -3 Z cutoff. At enrollment and months 2, 4, 6, 8, 10, 12,14,16,18,20,22,24 from enrollment, and at sick visits
Secondary Outcome Socioeconomic costs to the family defined as 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. Monthly for 24 months from enrollment, and at sick visits and days 7 and 28 post-sick visit follow-ups
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Ifakara Health Institute PO Box 74 Bagamoyo United Republic of Tanzania
FUNDING SOURCES
Name of source Street address City Postal code Country
NIH National Institute of Allergy and Infectious Diseases 5601 Fishers Lane, MSC 980 Bethseda MD 20892 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor University of California San Francisco 550 16th St San Francisco CA 94158 United States of America University
COLLABORATORS
Name Street address City Postal code Country
Stanford University 300 Pasteur Drive Stanford CA 94305 United States of America
Swiss Tropical and Public Health Institute Kreuzstrasse Allschwil 4123 Switzerland
National Institute of Allergy and Infectious Diseases 5601 Fishers Lane Bethseda MD 20892 United States of America
Ifakara Health Institute P.O. Box 74 Bagamoyo United Republic of Tanzania
Chan Zuckerberg Biohub 499 Illinois St San Francisco United States of America
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Michelle Hsiang michelle.hsiang@ucsf.edu +14155955978 550 16th St
City Postal code Country Position/Affiliation
San Francisco United States of America Associate Professor University of California San Francisco
Role Name Email Phone Street address
Public Enquiries Sylvia Jebiwott sylvia.jebiwott@ucsf.edu +1530601701 550 16th St
City Postal code Country Position/Affiliation
San Francisco United States of America Research Coordinator University of California San Francisco
Role Name Email Phone Street address
Scientific Enquiries Michelle Hsiang michelle.hsiang@ucsf.edu +14155955978 550 16th St
City Postal code Country Position/Affiliation
San Francisco United States of America Associate Professor University of California San Francisco
Role Name Email Phone Street address
Principal Investigator Ally Olotu aolotu@ihi.or.tz +255718927104 Plot 463 Kiko Avenue
City Postal code Country Position/Affiliation
Dar es Salaam United Republic of Tanzania IFAKARA HEALTH INSTITUTE Head of Intervention Trials
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes We will share the data after planned analyses are completed upon request and approval to the principal investigators Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol Upon completion of planned analyses and publication of main trial results Request and approval of PIs Planned analyses completed and main trial results published
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information