Clinical trial NCT04978272: Modifying Immunity in Children With DihydROartemisinin-Piperaquine (MIC-DroP)
Official title: Enhancing Immunity to Malaria in Young Children With Effective Chemoprevention
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Malaria
Keywords: dihydroartemisinin-piperaquine
intermittent preventive therapy
children
immune response
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Stanford University
name: Infectious Diseases Research Collaboration, Uganda
name: National Institute of Allergy and Infectious Diseases (NIAID)
name: Karolinska Institutet
First posted: 2021-07-27
Enrollment: 924
Sex: ALL
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Double blinded randomized controlled trial
Primary purpose: PREVENTION

Brief summary: The MIC-DroP trial will test the hypothesis that preventing early life blood-stage malaria antigenic exposure with intermittent preventive therapy (IPT) enhances protective immunity to malaria. This study will take advantage of a unique opportunity to study infants born to mothers followed in a NIH-funded randomized controlled trial of novel intermittent preventive therapy in pregnancy (IPTp) regimens (NCT04336189). MIC-DroP will leverage the parent IPTp study to enroll 924 children who will be randomized at 8 weeks of age to receive no intermittent preventive therapy in childhood (IPTc), monthly DP from 8 weeks to 1 year of age, or monthly DP from 8 weeks to 2 years of age, and then follow children to 4 years of age. The primary outcome of this study will be to compare the incidence of malaria from 2 to 4 years of age among children randomized to receive no IPTc, monthly DP for the first year of life, or monthly DP for the first two years of life. Investigators will also leverage this trial to evaluate immune development during early childhood.

Detailed description: This study is a phase III, double-blind, randomized controlled trial of 924 HIV- uninfected children. Children born to mothers enrolled in an ongoing clinical trial of different IPTp arms in pregnancy (NCT 04336189) will be enrolled in this study. In the parent IPTp study, 2757 HIV-uninfected pregnant women will be randomized to receive IPTp with monthly sulfadoxine pyrimethamine (SP) alone, monthly DP alone, or both monthly SP+DP, and followed through 4 weeks postpartum. At the 4-week postpartum visit, we will enroll and randomize 924 eligible children to one of three IPTc arms: no IPTc (the current standard of care), monthly DP from 8 weeks to 1 year of age, or monthly DP from 8 weeks to 2 years of age. Study drugs will be placebo controlled and all doses of study drug will be given by directly observed therapy (DOT). The intervention phase will be completed at 2 years of age, and children followed through 4 years of age. Study participants will be followed for all of their outpatient medical care in our dedicated study clinic. Malaria incidence will be measured via active case detection. Routine assessments will be performed in the study clinic for all study participants every 4 weeks, including passive surveillance for parasitemia by quantitive polymerase chain reaction (qPCR). Venous blood will be collected for immunologic assays three times annually from 8 weeks to 4 years of age. All maternal assessments conducted during the parent IPTp study, including assessment for maternal malaria exposure (e.g., placental histology) household survey, will be available and linked to each study participant.

Eligibility criteria: Inclusion Criteria:

1. Born to HIV-uninfected mother enrolled in parent clinical trial of intermittent preventative treatment of malaria in pregnancy (IPTp-SP vs. IPTp-DP vs. IPTp-SP+DP, NCT 04336189)
2. Resident of Busia District
3. Provision of informed consent by parent/guardian
4. Agreement to present for any illness and avoid, where possible, medications outside the study protocol.

Exclusion Criteria:

1. Intention of moving outside Busia district during the study period
2. Active medical problem requiring in-patient evaluation or chronic medical condition requiring frequent medical attention

Primary outcomes:
measure: Incidence of symptomatic malaria following cessation of IPTc
timeFrame: 2 years to 4 years of age
Secondary outcomes:
measure: Incidence of complicated malaria
timeFrame: 2 years to 4 years of age
measure: Incidence of hospital admissions and/or deaths
timeFrame: 2 years to 4 years of age
measure: Prevalence of parasitemia
timeFrame: 2 years to 4 years of age
measure: Prevalence of anemia
timeFrame: 2 years to 4 years of age
Other outcomes:
Locations:
city: Tororo
country: Uganda
facility: IDRC - Tororo Research Clinic
Study officials:
affiliation: Stanford University
name: Prasanna Jagannathan, MD
role: PRINCIPAL_INVESTIGATOR
References: