Clinical trial NCT07021430: Focal Mass Drug Administration for the Prevention of Malaria in Pregnancy
Official title: Focal Mass Drug Administration for the Prevention of Malaria in Pregnancy: a Pilot Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: EARLY_PHASE1
Conditions: Malaria Prevention
Keywords: Malaria
Focal mass drug administration
Dihydroartemisinin-piperaquine
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2025-06-15
Enrollment: 300
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to demonstrate the feasibility, acceptability, and preliminary effectiveness of a focal mass drug administration program for household members of pregnant women to protect against malaria in pregnancy.

Detailed description: The scientific objective of this pilot study is to demonstrate the feasibility, acceptability, and preliminary effectiveness of a focal mass drug administration program for household members of pregnant women to protect against Malaria in Pregnancy. The hypothesis is that eliminating the parasite reservoir within the household will provide a complementary layer of protection against Malaria in Pregnancy especially when access to care is limited and visits may be delayed or missed.

Aim 1: Determine the feasibility and acceptability of a Focal Mass Drug Administration program with dihydroartemisinin-piperaquine as a novel component of the Malaria in Pregnancy prevention package. The study team will conduct an open-label, randomized pilot study at a primary health center in rural western Uganda. The household members of women presenting to their first antenatal Clinic visit will be randomized 1:1:1: to (i) control (ii) one-time Focal Mass Drug Administration, or (iii) monthly Focal Mass Drug Administration. Using an established implementation framework, the study team will assess process measures such as the proportion of household members reached, willingness to take Dihydroartemisinin Piperaquine, adherence to the course of treatment, and frequency of adverse events.

Aim 2: Estimate the efficacy of Focal Mass Drug Administration to create a "safe zone" in the immediate home environment and ultimately prevent Malaria in Pregnancy. Using the study design outlined in Aim 1, The study team will follow participating pregnant women and associated households through delivery, including longitudinal assessments of P. falciparum infection. As a pilot study, the trial is deliberately not powered for statistical tests of significance, but The study team will measure the incidence of (i) clinical malaria, defined as the presence of typical symptoms (e.g., fever, lethargy) and a positive malaria rapid diagnostic test (Rapid Diagnostic Test), (ii) asymptomatic P. falciparum parasitemia and placental malaria by Polymerase Chain Reaction throughout pregnancy and (iii) the incidence of adverse birth outcomes (e.g., stillbirth, low birth weight). In addition, the study team will measure the prevalence of asymptomatic parasitemia in household members using Rapid Diagnostic Tests at three time points to estimate the effectiveness of Focal Mass Drug Administration at maintaining a parasite-free zone

Eligibility criteria: Inclusion Criteria:

* Primary residence (i.e., where a person lives for ≥ 6 months per year) in Kasese District with no plans to change residency in subsequent 6 months
* Able and willing to comply with all study procedures and be available for the duration of the study
* Able and willing to consent to study procedures as documented on informed consent form. For children (age \<18 years), parent or guardian must provide consent. Children age ≥8 to 17 years will also be asked to provide written assent.

Each pregnant women will also need to meet additional eligibility criteria:

18 years old or older Presenting to Bugoye Level III Health Center for antenatal care and plan to deliver at Bugoye Level III Health Center (i.e., not planned cesarean section) Gestational age ≤22 weeks Human Immunodeficiency Virus negative

Exclusion Criteria:

* An individual who meets any of the following criteria will be excluded from participation:
* Temporary or part-time residence in Kasese District (i.e., where a person lives for \< 6 months per year)
* Known plans to move within the next 6 months
* Unable or unwilling to provide consent
* Anything that would place the individual at increased risk or preclude the individual's full compliance with or completion of the study

In addition, individuals with any of the following will still be eligible to participate (e.g,, complete surveys, provide blood samples) but will not be eligible to receive Dihydroartemisinin Piperaquine if randomized to one of the intervention arms:

* Known arrythmia, QT prolongation, or seizure disorder will not be eligible to receive Dihydroartemisinin Piperaquine
* Use of potentially contraindicated medications outlined in Section 5.6
* Weight \<5 kg
* Known allergic reaction to Dihydroartemisinin Piperaquine or other Artemisinin Combination Therapies

Primary outcomes:
measure: Percent of eligible household members receiving fMDA
timeFrame: Day 1 to study completion, generally 5 months
Secondary outcomes:
measure: Percent of household members enrolled
timeFrame: At enrollment visit (Day 1)
measure: Refusal to receive fMDA
timeFrame: Day 1 to study completion, generally 5 months
measure: fMDA Adherence
timeFrame: Day 1 to study completion, generally 5 months
measure: P. falciparum parasitemia among household members
timeFrame: Day 1 to study completion, generally 5 months
measure: P. falciparum parasitemia among pregnant women
timeFrame: Day 1 to study completion, generally 5 months
measure: P. falciparum parasitemia in peripheral and placental blood at delivery
timeFrame: At time of birth/delivery
measure: Clinical malaria incidence among pregnant women
timeFrame: Day 1 to study completion, generally 5 months
measure: Maternal anemia
timeFrame: Day 1 to study completion, generally 5 months
measure: Adverse birth outcomes
timeFrame: Day 1 to study completion, generally 5 months
measure: Co-occurrence of malaria parasitemia in mother and household members
timeFrame: Day 1 to study completion, generally 5 months
measure: Number of adverse reactions to DP
timeFrame: Day 1 to study completion, generally 5 months
Other outcomes:
Locations:
city: Kasese
country: Uganda
facility: Bugoye Level III Health Center
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Ross Boyce, MD
role: PRINCIPAL_INVESTIGATOR
References: