Malaria
Conditions
Keywords
mosquito, ivermectin, Anopheles, Plasmodium
Brief summary
RIMDAMAL II is a double-blind, cluster randomized trial in Burkina Faso designed to test whether repeated ivermectin mass drug administrations, integrated into a monthly delivery platform with standard malaria control measures of seasonal malaria chemoprevention and insecticide-treated bed net distribution in the Sahel, will reduce childhood malaria incidence.
Detailed description
The RIMDAMAL II trial is designed to determine the efficacy of adding seasonal ivermectin mass drug administrations to the standard-policy malaria control measures in the Sahel (seasonal malaria chemoprevention in children, maximum long-lasting insecticidal net coverage, intermittent preventive treatment in pregnancy), for reducing the incidence of uncomplicated malaria episodes in enrolled village children (≤ 10 years of age) assessed by active case surveillance. The investigators will also examine the safety of the intervention, as well as entomological and parasitological endpoints. This is a double-blind, cluster randomized trial in that will occur in villages in southwestern Burkina Faso over two consecutive rainy seasons. For the intervention, mass administration of ivermectin or placebo will be given monthly over 4 months of each rainy season to the eligible village population, each as 3-day course of 300 µg/kg/day. These mass drug administrations will occur simultaneously with the distribution of seasonal malaria chemoprevention drugs on the same monthly schedule to eligible children aged 3-59 months.
Interventions
DRUGIvermectin
Ivermectin (6 mg tablet) given monthly from July-October each rainy season as a 3-day course of approximately 300 mcg/kg/day as estimated by height bands.
DRUGPlacebo oral tablet
placebo in the same size, color and shape at the ivermectin tablet
Sponsors
Yale University
Institut de Recherche en Sciences de la Sante-Direction Regionale de l'Ouest
Radboud University Medical Center
PATH
National Institute of Allergy and Infectious Diseases (NIAID)
Brian Foy
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The study pharmacist in charge of the drug stock room will originate the masking and maintain the masking from all other investigators. The masking codes will be written on three paper copies and put in identical and sealed opaque envelopes, which will be kept in three different areas.
Intervention model description
Parallel-assignment trial with two arms randomized in a 1:1 ratio.
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
Inclusion criteria
(for being enrolled in the study): * Residence in selected study village * Able to understand the information and willing to give consent or assent (age 12-18) and parent/guardian consent if study participant age is \< 18 years of age.
Exclusion criteria
(for participating in the intervention \[ivermectin or placebo MDA\]): * Residence outside of the study village * Height \< 90 cm (\*note: if subject becomes ≥90cm over course the trial, this
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Malaria Incidence | up to 8 months | Incidence of malaria episodes in enrolled village children ≤ 10 years of age |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | up to 8 months | Number adverse events among the study population over the course of the intervention period. Note, this number includes all malaria cases that were part of the primary outcome that occurred in the cohort of children that were actively assessed for malaria on a weekly basis during the intervention. |
| Survival Rate of Blood Fed Mosquitoes | up to 8 months | Number of Blood Fed Mosquitoes Alive For 3 Days After Capture |
Countries
Burkina Faso
Participant flow
Recruitment details
Potential clusters (villages) within the Diebougou Health district, Burkina Faso, were identified from a catchment area based on access, safety of the study team, potential for contamination, and cluster size, and invited to participant via an extensive community engagement process.
Participants by arm
| Arm | Count |
|---|---|
| Ivermectin Mass Drug Administration Ivermectin given monthly from July-October (4 times) as a 3-day course of 300 µg/kg/day to all eligible persons per exclusion/inclusion criteria. Per package insert, dosing of IVM will be according to height to approximate weight: 90-119 cm = 1 tablet/day for 3 days; 120-140 cm = 2 tablets/day for 3 days; 141-158 cm = 3 tablets/day for 3 days; \>158 cm = 4 tablet/day for 3 days.
Ivermectin: Ivermectin (6 mg tablet) given monthly from July-October each rainy season as a 3-day course of approximately 300 mcg/kg/day as estimated by height bands. | 2,191 |
| Placebo Mass Administration Placebo given monthly from July-October (4 times) as a 3-day course to all eligible persons per exclusion/inclusion criteria. Dosing of placebo will be according to height to approximate weight: 90-119 cm = 1 tablet/day for 3 days; 120-140 cm = 2 tablets/day for 3 days; 141-158 cm = 3 tablets/day for 3 days; \>158 cm = 4 tablet/day for 3 days.
Placebo oral tablet: placebo in the same size, color and shape at the ivermectin tablet | 1,933 |
| Total | 4,124 |
Baseline characteristics
| Characteristic | Ivermectin Mass Drug Administration | Total | Placebo Mass Administration |
|---|---|---|---|
| Age, Continuous | 17 years | 16 years | 15 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2191 Participants | 4124 Participants | 1933 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Burkina Faso | 2191 participants | 4124 participants | 1933 participants |
| Sex: Female, Male Female | 1100 Participants | 2124 Participants | 1024 Participants |
| Sex: Female, Male Male | 1091 Participants | 2000 Participants | 909 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 6 / 2,191 | 3 / 1,933 |
| other Total, other adverse events | 430 / 2,191 | 396 / 1,933 |
| serious Total, serious adverse events | 8 / 2,191 | 6 / 1,933 |
Outcome results
Primary
Malaria Incidence
Incidence of malaria episodes in enrolled village children ≤ 10 years of age
Time frame: up to 8 months
Population: The primary outcome measure comes only from malaria incidence measurements within a cohort of village children (1531). It is not a measure of malaria incidence from all enrolled participants from the study villages. The majority of participants (1133/1531) within the child cohort were evaluated in both years, meaning that they contributed a malaria case count for both year 1 and year 2.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Ivermectin Mass Drug Administration | Malaria Incidence | 0.0176 Malaria cases per person-week |
| Placebo Mass Administration | Malaria Incidence | 0.0183 Malaria cases per person-week |
Secondary
Adverse Events
Number adverse events among the study population over the course of the intervention period. Note, this number includes all malaria cases that were part of the primary outcome that occurred in the cohort of children that were actively assessed for malaria on a weekly basis during the intervention.
Time frame: up to 8 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ivermectin Mass Drug Administration | Adverse Events | 438 adverse events |
| Placebo Mass Administration | Adverse Events | 402 adverse events |
Secondary
Survival Rate of Blood Fed Mosquitoes
Number of Blood Fed Mosquitoes Alive For 3 Days After Capture
Time frame: up to 8 months
Population: This analysis population is not human participants but mosquitoes captured from participants' homes. These are blood fed Anopheles gambiae s.l. mosquitoes captured indoors in participants' home 1 week following each mass drug administration.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Ivermectin Mass Drug Administration | Survival Rate of Blood Fed Mosquitoes | 399 mosquitoes |
| Placebo Mass Administration | Survival Rate of Blood Fed Mosquitoes | 896 mosquitoes |