MalariaPhase 2/3RIMDAMALNCT02509481
Repeat Ivermectin Mass Drug Administrations for Control of Malaria: a Pilot Safety and Efficacy Study
A Phase 2/3 study testing Ivermectin and Albendazole in people with Malaria and Lymphatic Filariasis, run by Colorado State University at 2 sites in 2 countries.
Trial summary
The purpose of this study is to determine whether repeated ivermectin mass drug administrations to Burkinabé villagers, performed in three week intervals over the rainy-season, is well-tolerated and safe, and also effective in reducing local malaria transmission and thus clinical malaria episodes in treated village… Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Malaria, Lymphatic Filariasis
- What is being tested?
- Ivermectin and Albendazole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,712 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Jun 2015to Dec 2015
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Residence in the study site
- Able to understand the information and willing to give consent and assent (parent or guardian consent if study participant age is < 18 years)
Who cannot join
- Residence outside of in the study site
- Height ≤ 90 cm
- Permanent disability, serious medical illness that prevents or impedes study participation and/or comprehension
- Pregnancy
- Breast feeding if infant is within 1 week of birth
- Known allergy to the study drugs
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
Colorado State University
Fort Collins, Colorado, 80523
Burkina Faso1 site
Institut de Recherche en Sciences de la Santé
Bobo-Dioulasso, Houet, 10400-000
About this study
The purpose of this study is to determine whether repeated ivermectin mass drug administrations to Burkinabé villagers, performed in three week intervals over the rainy-season, is well-tolerated and safe, and also effective in reducing local malaria transmission and thus clinical malaria episodes in treated village children.
Read the detailed description
Primary Objective: To determine the efficacy of repeated ivermectin mass drug administrations (IVM MDA) (150 µg/kg), given to the population of eligible patients in enrolled villages, for reducing the cumulative incidence of uncomplicated malaria episodes in enrolled village children (≤ 5 years of age) over the course of the treatment.
Hypothesis: Repeated IVM MDA starting at the beginning of the rainy season will be well tolerated and safe, and will reduce clinical malaria episodes in children by significantly reducing malaria transmission among treated villages.
Overview Study Design: Single-blind (outcomes assessor); parallel assignment with 2 arms; cluster-randomized control trial to determine the effect of repeated IVM MDA on malaria transmission and clinical malaria episodes. The unit of randomization will be the village (cluster). 8 villages total will be enrolled in two arms. The active comparator arm (4 villages) will receive a single standard MDA (IVM; 150-200 µg/kg + albendazole; 400 mg) soon after the start of the rainy season, while the experimental arm (4 villages) will receive the standard MDA on the same date, plus 5 more IVM MDA at 3 week intervals thereafter. The primary endpoint will be the cumulative incidence of clinical malaria episodes in children ≤5 year of age within each village.
Sites: This study will be conducted in villages along the main east-west and north-south road corridors in the Sud-Ouest administrative region of Burkina Faso.
Study Population: Indigenous Burkinabé from various ethnic groups (Dagara, Bobo, Lobi, Mossi, etc.). The entire eligible population of each enrolled village will receive the MDAs, following the standard inclusion/exclusion criteria of MDA for control of microfilaremia caused by Wuchereria bancrofti (lymphatic filariasis; LF). Clinical incidence of malaria will be assessed only in children living in enrolled villages who are ≤ 5 years of age, most of whom will not have received any treatment due to the standard MDA exclusion criteria of children < 90 cm.
Study Interventions: 2 arms: 1) Active comparator arm - single standard MDA with IVM (150 µg/kg) + albendazole (ALB;400 mg) soon after the beginning of the rainy season; 2) Experimental arm, single standard MDA with IVM (150 µg/kg) + ALB (400 mg) plus 5 more MDA with IVM alone (150 µg/kg) at 3 week intervals thereafter. Community health workers and trained by local health authority of the Sud-Ouest region will perform the first MDA in both arms with logistical assistance from the study investigators. Repeated MDAs will only occur in the experimental-arm villages, and be performed by the study investigators.
Follow-up Procedures: Trained nurses will visit each study village each week over the course of the study to investigate and record any adverse events or severe adverse events communicated by the study population. They will also perform active case surveillance each week on enrolled village children for clinical malaria episodes, defined as ≥38.0°C fever or history of fever in the last 24 hours + positive rapid diagnostic test for Plasmodium falciparum. Secondary measures will be collected by the nurses.
Sample Size: Assuming an 80% cumulative incidence of malaria episodes in the control arm and an intracluster correlation coefficient of 0.02, 4 clusters are needed per arm and 69 children enrolled per cluster to detect a conservative 40% reduction in incidence in the treatment arm with 80% power and a statistical confidence of 95%.
Safety Outcomes:
- Adverse events (seriousness, causality, expectedness)
Secondary Outcomes:
- Incidence of new P. falciparum infections acquired (molecular force-of-infection)
- Prevalence and intensity (eggs/larvae per gram of feces) of soil transmitted helminth infections in a subset of treated patients between 6-10 years of age.
- Indoor-resting Anopheles mosquito capture rate
- Outdoor-host seeking Anopheles mosquito capture rate
- Adult mosquito age structure (parity rate) in captured mosquitoes
- Plasmodium sporozoite rate/entomological inoculation rate in captured mosquitoes
- Rate of Wuchereria bancrofti in captured mosquitoes
- Conditions
- Malaria, Lymphatic Filariasis
- Being tested
- Ivermectin, Albendazole
- Keywords
- malaria, lymphatic filariasis, mosquito, ivermectin, mass drug administration
- Medical subject headings
- Malaria, Elephantiasis, Filarial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IvermectinDrug
Also called Mectizan
AlbendazoleDrug
| Study group | Role | What they receive |
|---|---|---|
| Single MDA | Active comparator | Single mass drug administration of ivermectin (150 µg/kg) + albendazole (400 mg) performed after the start of the rainy season as part of public health efforts to eliminate lymphatic filariasis. Receives: Drug: Ivermectin; Drug: Albendazole |
| Repeated MDA | Experimental | Same at Active Comparator, but then followed by five more mass drug administrations of ivermectin only (150 µg/kg) every three weeks thereafter. Receives: Drug: Ivermectin; Drug: Albendazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Clinical Malaria Episodes
Cumulative incidence of malaria episodes in a cohort of village children ≤ 5 years of age (as assessed by active case surveillance in study villages - malaria episode defined as ≥38.0°C fever or history of fever in the last 24 hours + positive rapid diagnostic test for Plasmodium falciparum). Incidence is reported as malaria episodes per child over the course of the trial, a higher incidence is a worse outcome.
Measured: Approximately 18 weeks, from the start of the first MDA to 3 weeks following the last MDA in the Experimental arm
Secondary outcomes (5)
Adverse Events
The number of adverse events. Adverse events data were collected via passive case detection from total population.
Measured: Approximately 18 weeks, from the start of the first MDA to 3 weeks following the last MDA in the Experimental arm
Entomological Indicator of Parasite Transmission
Change in human IgG reactivity (optical density; ∆OD) to an Anopheles salivary gland antigen (peptide gSG6-P1) over the trial period. A score of 0 indicates no change in seroreactivity from from immediately before to immediately after the trial, suggesting consistent mosquito biting throughout the trial. A positive score indicates increasing seroreactivity and thus increasing mosquito biting on participants from immediately before to immediately after the trial. A negative score indicates decreasing seroreactivity and thus decreasing mosquito biting on participants from immediately before to immediately after the trial.
Measured: Approximately 20 weeks, from before the start of the first MDA to 4 weeks following the last MDA in the Experimental arm
Molecular Force of P. Falciparum Infection
Examination of new P. falciparum clones acquired from the beginning to the end of the intervention (molecular force of infection; mFOI) per child. Molecular genotyping used capillary blood taken at the time of diagnosis of each positive malaria episode and consisted of nPCR of the msp2 gene. We calculated the multiplicity of infection (MOI) per malaria episode, and then calculated the molecular force of infection (mFOI) associated with malaria episodes per child (over course of the trial)
Measured: Approximately 18 weeks, from the start of the first MDA to 3 weeks following the last MDA in the Experimental arm
Number of 6-10 Year Old Participants With Soil Transmitted Helminths (STH)
Prevalence of soil transmitted helminth infections in children between 6-10 years old from the beginning to the end of the intervention
Measured: Approximately 20 weeks, from before the start of the first MDA to 4 weeks following the last MDA in the Experimental arm
Entomological Inoculation Rate
The entomological inoculation rate (EIR per week per person) is the measure of the human biting rate per person per week, multiplied by the sporozoite rate (in biting mosquitoes) per week, an estimated from sampling mosquitoes from 8 households located in the center of each study village. The EIR was calculated for each of the 6 sampling weeks of the treatment phase.
Measured: 6 sampling periods over 18 weeks, starting in week 2 following the first MDA, and sampling every 3 weeks thereafter until week 17 of the treatment phase.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2015 (estimated)
- Study startJun 2015
- Primary completionNov 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 2,712 participants (actual)
Sponsor and investigators
- Lead sponsor
- Colorado State University
- Sponsor type
- University, hospital or other
- Collaborators
- Institut de Recherche en Sciences de la Sante, Burkina Faso, Centre Muraz, Ministère de la Santé du Burkina Faso
- Responsible party
- Sponsor
- Investigators
- Brian D. Foy, PhD, Principal investigator, Colorado State UniversityRoch K Dabire, PhD, Principal investigator, Institute de Recherche en Sciences de la Santé
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02509481
- Sponsor's protocol ID
- 5375011
- Other IDs
- OPP1116536
- Acronym
- RIMDAMAL
- Status last verified
- Jan 2019
- First submitted
- 23 Jul 2015
- Last updated
- 4 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Foy BD, Alout H, Seaman JA, Rao S, Magalhaes T, Wade M, Parikh S, Soma DD, Sagna AB, Fournet F, Slater HC, Bougma R, Drabo F, Diabate A, Coulidiaty AGV, Rouamba N, Dabire RK. Efficacy and risk of harms of repeat ivermectin mass drug administrations for control of malaria (RIMDAMAL): a cluster-randomised trial. Lancet. 2019 Apr 13;393(10180):1517-1526. doi: 10.1016/S0140-6736(18)32321-3. Epub 2019 Mar 14.
PubMed 30878222
Study at a glance
From the registry record, last updated by the sponsor on 4 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Repeat Ivermectin Mass Drug Administrations for Control of Malaria: a Pilot Safety and Efficacy Study
- ClinicalTrials.gov ID
- NCT02509481
- Acronym / sponsor ID
- RIMDAMAL / 5375011
- Conditions
- Malaria, Lymphatic Filariasis
- Keywords
- malaria, lymphatic filariasis, mosquito, ivermectin, mass drug administration
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,712 participants (actual)
- Lead sponsor
- Colorado State UniversityUniversity, hospital or other
- Collaborators
- Institut de Recherche en Sciences de la Sante, Burkina Faso, Centre Muraz, Ministère de la Santé du Burkina Faso
- Study start
- Jun 2015
- Primary completion
- Nov 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 28 Jul 2015 (estimated)
- Results
- Posted 4 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether repeated ivermectin mass drug administrations to Burkinabé villagers, performed in three week intervals over the rainy-season, is well-tolerated and safe, and also effective in reducing local malaria transmission and thus clinical malaria episodes in treated village children.
Detailed description
Primary Objective: To determine the efficacy of repeated ivermectin mass drug administrations (IVM MDA) (150 µg/kg), given to the population of eligible patients in enrolled villages, for reducing the cumulative incidence of uncomplicated malaria episodes in enrolled village children (≤ 5 years of age) over the course of the treatment.
Hypothesis: Repeated IVM MDA starting at the beginning of the rainy season will be well tolerated and safe, and will reduce clinical malaria episodes in children by significantly reducing malaria transmission among treated villages.
Overview Study Design: Single-blind (outcomes assessor); parallel assignment with 2 arms; cluster-randomized control trial to determine the effect of repeated IVM MDA on malaria transmission and clinical malaria episodes. The unit of randomization will be the village (cluster). 8 villages total will be enrolled in two arms. The active comparator arm (4 villages) will receive a single standard MDA (IVM; 150-200 µg/kg + albendazole; 400 mg) soon after the start of the rainy season, while the experimental arm (4 villages) will receive the standard MDA on the same date, plus 5 more IVM MDA at 3 week intervals thereafter. The primary endpoint will be the cumulative incidence of clinical malaria episodes in children ≤5 year of age within each village.
Sites: This study will be conducted in villages along the main east-west and north-south road corridors in the Sud-Ouest administrative region of Burkina Faso.
Study Population: Indigenous Burkinabé from various ethnic groups (Dagara, Bobo, Lobi, Mossi, etc.). The entire eligible population of each enrolled village will receive the MDAs, following the standard inclusion/exclusion criteria of MDA for control of microfilaremia caused by Wuchereria bancrofti (lymphatic filariasis; LF). Clinical incidence of malaria will be assessed only in children living in enrolled villages who are ≤ 5 years of age, most of whom will not have received any treatment due to the standard MDA exclusion criteria of children < 90 cm.
Study Interventions: 2 arms: 1) Active comparator arm - single standard MDA with IVM (150 µg/kg) + albendazole (ALB;400 mg) soon after the beginning of the rainy season; 2) Experimental arm, single standard MDA with IVM (150 µg/kg) + ALB (400 mg) plus 5 more MDA with IVM alone (150 µg/kg) at 3 week intervals thereafter. Community health workers and trained by local health authority of the Sud-Ouest region will perform the first MDA in both arms with logistical assistance from the study investigators. Repeated MDAs will only occur in the experimental-arm villages, and be performed by the study investigators.
Follow-up Procedures: Trained nurses will visit each study village each week over the course of the study to investigate and record any adverse events or severe adverse events communicated by the study population. They will also perform active case surveillance each week on enrolled village children for clinical malaria episodes, defined as ≥38.0°C fever or history of fever in the last 24 hours + positive rapid diagnostic test for Plasmodium falciparum. Secondary measures will be collected by the nurses.
Sample Size: Assuming an 80% cumulative incidence of malaria episodes in the control arm and an intracluster correlation coefficient of 0.02, 4 clusters are needed per arm and 69 children enrolled per cluster to detect a conservative 40% reduction in incidence in the treatment arm with 80% power and a statistical confidence of 95%.
Safety Outcomes:
- Adverse events (seriousness, causality, expectedness)
Secondary Outcomes:
- Incidence of new P. falciparum infections acquired (molecular force-of-infection)
- Prevalence and intensity (eggs/larvae per gram of feces) of soil transmitted helminth infections in a subset of treated patients between 6-10 years of age.
- Indoor-resting Anopheles mosquito capture rate
- Outdoor-host seeking Anopheles mosquito capture rate
- Adult mosquito age structure (parity rate) in captured mosquitoes
- Plasmodium sporozoite rate/entomological inoculation rate in captured mosquitoes
- Rate of Wuchereria bancrofti in captured mosquitoes
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Single MDA | Active comparator | Drug: Ivermectin, Drug: AlbendazoleSingle mass drug administration of ivermectin (150 µg/kg) + albendazole (400 mg) performed after the start of the rainy season as part of public health efforts to eliminate lymphatic filariasis. |
| Repeated MDA | Experimental | Drug: Ivermectin, Drug: AlbendazoleSame at Active Comparator, but then followed by five more mass drug administrations of ivermectin only (150 µg/kg) every three weeks thereafter. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Residence in the study site
- Able to understand the information and willing to give consent and assent (parent or guardian consent if study participant age is < 18 years)
Key exclusion criteria (6 listed)
- Residence outside of in the study site
- Height ≤ 90 cm
- Permanent disability, serious medical illness that prevents or impedes study participation and/or comprehension
- Pregnancy
- Breast feeding if infant is within 1 week of birth
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IvermectinAlso: Mectizan | Drug | Repeated MDA, Single MDA |
| Albendazole | Drug | Repeated MDA, Single MDA |
Primary outcome
Incidence of Clinical Malaria Episodes
Time frame: Approximately 18 weeks, from the start of the first MDA to 3 weeks following the last MDA in the Experimental arm
Cumulative incidence of malaria episodes in a cohort of village children ≤ 5 years of age (as assessed by active case surveillance in study villages - malaria episode defined as ≥38.0°C fever or history of fever in the last 24 hours + positive rapid diagnostic test for Plasmodium falciparum). Incidence is reported as malaria episodes per child over the course of the trial, a higher incidence is a worse outcome.
5 secondary outcomes
Adverse Events
Time frame: Approximately 18 weeks, from the start of the first MDA to 3 weeks following the last MDA in the Experimental arm
Entomological Indicator of Parasite Transmission
Time frame: Approximately 20 weeks, from before the start of the first MDA to 4 weeks following the last MDA in the Experimental arm
Molecular Force of P. Falciparum Infection
Time frame: Approximately 18 weeks, from the start of the first MDA to 3 weeks following the last MDA in the Experimental arm
Number of 6-10 Year Old Participants With Soil Transmitted Helminths (STH)
Time frame: Approximately 20 weeks, from before the start of the first MDA to 4 weeks following the last MDA in the Experimental arm
Entomological Inoculation Rate
Time frame: 6 sampling periods over 18 weeks, starting in week 2 following the first MDA, and sampling every 3 weeks thereafter until week 17 of the treatment phase.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30878222Foy BD, Alout H, Seaman JA, Rao S, Magalhaes T, Wade M, Parikh S, Soma DD, Sagna AB, Fournet F, Slater HC, Bougma R, Drabo F, Diabate A, Coulidiaty AGV, Rouamba N, Dabire RK. Efficacy and risk of harms of repeat ivermectin mass drug administrations for control of malaria (RIMDAMAL): a cluster-randomised trial. Lancet. 2019 Apr 13;393(10180):1517-1526. doi: 10.1016/S0140-6736(18)32321-3. Epub 2019 Mar 14.
Related trials for Malaria
Active, not recruitingObservational study
Trajectories and Mechanisms of Recovery From Malaria: An Observational Study
Malaria
Not yet recruiting
Positron Emission Tomography and Organ-Specific Changes in Participants Co-Enrolled in NIH Studies of Plasmodium Vivax Controlled Human Malaria Infection
Healthy Volunteer, Malaria
Recruiting
The Effects of Iron Treatment on Vaccine Immunogenicity in Kenyan Infants With Iron Deficiency
Iron Deficiencies
RecruitingObservational study
Host and Parasite Factors That Influence Susceptibility to Malaria Infection and Disease During Pregnancy and Early Childhood in Ouelessebougou and Bamako, Mali
Malaria
RecruitingPhase 1
Safety, Tolerability and Efficacy of PfSPZ-LARC2 Vaccine Against CHMI in Malaria-Naïve Adults
Malaria Falciparum
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brian D. Foy, PhD principal investigator
Colorado State University
Roch K Dabire, PhD principal investigator
Institute de Recherche en Sciences de la Santé
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Ivermectin and Albendazole in people with Malaria and Lymphatic Filariasis, run by Colorado State University at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Burkina Faso. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Clinical Malaria Episodes (time frame: Approximately 18 weeks, from the start of the first MDA to 3 weeks following the last MDA in the Experimental arm). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02509481, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jan 2019.