A Community Setting Study of Malaria After Systematic Treatment of Symptomatic Carriers of P. Falciparum With COA566 (Coartem®)

Study Overview
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Brief Summary
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This study assessed the impact of the systematic detection by Rapid Diagnostic Test (RDT) and treatment of asymptomatic carriers of malaria parasites (P. falciparum) with COA566 on a number of clinical malaria cases in children less than 5 years of age and the improvement of hemoglobin levels in the overall population.

Official Title
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A Cluster Randomized, Single-centre, Controlled, Parallel,12-month Prospective Study and Additional 12-month Follow-up in Africa of Malaria Incidence in a Community Setting Following Systematic Treatment of P. Falciparum Asymptomatic Carriers With Artemether-lumefantrine (Coartem® / Coartem® Dispersible)

Conditions
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Malaria

Intervention / Treatment
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* Drug: COA566


Participation Criteria
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Eligibility Criteria
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Inclusion: Subjects who were diagnosed as Asymptomatic Carrier (AC) by Rapid Diagnostic Test (RDT). Subjects who were diagnosed with a Symptomatic malaria episode, RDT-confirmed (SMRC) Exclusion: Body weight <5 kg. Hypersensitivity to artemether-lumefantrine or to any of the excipients of the tablets or dispersible tablets. Presence of severe malaria signs and symptoms First trimester of pregnancy. Family history of congenital prolongation of the QTc interval or sudden death or with any other clinical condition known to prolong the QTc interval such as history of symptomatic cardiac arrhythmias, with clinically relevant bradycardia or with severe cardiac disease. Taking drugs that are known to influence cardiac function and to prolong QTc interval, such as class IA and III: neuroleptics, antidepressant agents, certain antibiotics including some agents of the following classes: macrolides, fluoroquinolones, imidazole and triazole antifungal agents, certain non-sedating antihistamines. Known disturbances of electrolyte balance, e.g. hypokalemia or hypomagnesemia. Taking drugs which may be metabolized by cytochrome enzyme CYP2D6
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Participants received COA566 treatment for asymptomatic carriage of P. falciparum and for symptomatic malaria episodes. | Drug: COA566<br>* COA566 tablets or dispersible tablets twice daily during 3 days; dosage according to body weight.<br>* Other names: Artemether-lumefantrine;|
| Experimental: Control<br>Participants received COA566 treatment for symptomatic malaria episodes only. | Drug: COA566<br>* COA566 tablets or dispersible tablets twice daily during 3 days; dosage according to body weight.<br>* Other names: Artemether-lumefantrine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL (SMRC5000s) Per Person-year in Infants and Children (<5 Years) in Post Community Screening Campaign (CSC) at Month 12 (Per Cluster) | Data is presented per cluster. Number of Symptomatic malaria episode, RDT-confirmed, with parasitemia ≥5000/μL (SMRC5000s) per person-year in infants and children (<5 years) in post Community Screening Campaign (CSC) at month 12 was detected by Rapid Diagnostic Test (RDT) (using a blood sample from each participant) and later confirmed to have a parasite density ≥5000/uL by microscopy. Number of SMRC5000: sum of all SMRC5000 for all infants and children (<5 years) in post CSC. Person-year observed: sum of duration (in days) for all infants and children (<5 years) in post CSC present in study /365.25. Number of SMRC5000 per person-year = number of SMRC5000/person-year observed. | Month 12 of period 1 | 
| Change in Hemoglobin Level (g/dL) in Asymptomatic Carriers >6 Months of Age (Per Cluster) | Data is presented per cluster. Change in hemoglobin levels from day 1 to day 28 was measured using the HemoCue® rapid test. This test was performed using a drop of blood collected from the fingertip of each asymptomatic carrier from Community Screening Campaign 1 (CSC1), > 6 months of age, at day 1 and at day 28. | Day 1 and day 28 of period 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microscopy-confirmed Gametocyte Carriers at Community Screening Campaign 4 (CSC4) (Per Cluster) | Data is presented per cluster. Microscopy confirmed gametocyte carriers at Community Screening Campaign 4(CSC4) were assessed via microscopy at month 12 of period 1. Blood films were histologically treated and examined microscopically. | Month 12 - period 1 | 
| Microscopy Confirmed Asymptomatic Carriers of P. Falciparum at Community Screening Campaign 4 (CSC4) (Per Cluster) | Data is presented per cluster. Microscopy confirmation of asymptomatic carriers of P. falciparum at Community Screening Campaign 4 (CSC4) was conducted at month 12. Blood films were histologically treated and examined microscopically. When it was ascertained that P. falciparum was present, a count of the asexual forms against leukocytes was made using a tally counter. | Month 12 - period 1 | 
| Change in Hemoglobin Level (g/dL) From Community Screening Campaign 1(CSC1)/Day 1 to Community Screening Campaign 4 (CSC4)/Day 1 (Per Cluster) | Data is presented per cluster. Comparison of hemoglobin level (g/dL) from Community Screening Campaign 1 (CSC1)/Day 1 to Community Screening Campaign 4 (CSC4)/Day 1 in infants and children (>6 months and <5 years) by study arm was measured using the HemoCue® rapid test. This test was performed using a drop of blood collected from the fingertip of each participant. | Day 1 (CSC1/day 1) and month 12 (CSC4/day 1) - period 1 | 
| Number of Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL (SMRC5000s) Per Person-year in Post Community Screening Campaign (CSC) | Number of Symptomatic malaria episode, RDT-confirmed, with parasitemia ≥5000/μL (SMRC5000s) per person-year in post Community Screening Campaign (CSC), by study arm (individual level data) was detected by Rapid Diagnostic Test (RDT) (using a blood sample from each participant) and later confirmed to have a parasite density ≥5000/uL by microscopy. Number of SMRC5000: sum of all SMRC5000 for all subjects in post CSC. Person-year observed: sum of duration (in days) in post CSC for all subjects present in study /365.25. Number of SMRC5000 per person-year = number of SMRC5000/person-year observed. | 12 months - period 1 | 
| Number of Participants With Hospitalizations, Severe Malaria Episodes or Death Post Community Screening Campaign (CSC) | Total number of participants (all ages) with hospitalizations, severe malaria episodes or death after Community Screening Campaign (CSC) was assessed. | 12 months - period 1 | 
| Number of Participants (Infants and Children (> 6 Months and < 5 Years)) With Hospitalizations, Severe Malaria Episodes or Death Post Community Screening Campaign (CSC) | Total number of participants (infants and children (> 6 months and < 5 years)) with hospitalizations, severe malaria episodes or death after Community Screening Campaign (CSC) was assessed. | 12 months - period 1 | 
| Mean of Microscopy-confirmed Asymptomatic Carriers From Community Screening Campaigns 1, 2, 3 and 4 (CSC1, CSC2, CSC3 and CSC4) (Per Cluster) | Data is presented per cluster. Mean number of asymptomatic carriers from Community Screening Campaigns 1, 2, 3 and 4 (CSC1, CSC2, CSC3 and CSC4) was measured by confirmed positive microscopy for P. falciparum asexual forms in participants with absence of clinical signs and symptoms of malaria. Mean measured in this analysis is the mean percent indicting the mean of percentages of cluster frequencies under the study arm for that particular category. | 12 months - period 1 | 
| Mean Number of Microscopy-confirmed Gametocyte Carriers at Day 1 of Community Screening Campaign 1,2,3,4 (CSC1, CSC2, CSC3 and CSC4) (Per Cluster) | Data is presented per cluster. Mean number of gametocyte carriers at Day 1 for Community Screening Campaign 1,2,3,4 (CSC1, CSC2, CSC3 and CSC4) was measured using gametocyte assessments (prevalence and density) via microscopy. Mean measured in this analysis is the mean percent indicating the mean of percentages of cluster frequencies under the study arm for that particular category. | 12 months - period 1 | 
| Number of Microscopy and qRT-PCR-confirmed Gametocyte Carriers at Community Screening Campaign 4 (CSC4) | Number of gametocyte carriers at Community Screening Campaign 4 (CSC4) was measured via microscopy and confirmed using Quantitative Reverse Transcription PCR (qRT-PCR) at day 1 of CSC4. | Month 12 (CSC4/day 1) - period 1 | 
| Change in Hemoglobin Level (g/dL) From Community Screening Campaign 1 (CSC1)/Day 1 to CSC1/Day 28 in Infants and Children (>6 Months and <5 Years) for Asymptomatic Carriers at CSC1 | Change in hemoglobin level (g/dL) from Community Screening Campaign 1 (CSC1)/Day 1 to CSC1/Day 28 in infants and children (>6 Months and <5 Years) for asymptomatic carriers at CSC1 was measured via hemoglobin levels using the HemoCue® rapid test. This test was performed using a drop of blood collected from the fingertip of each participant. The anemic status is defined as follows: hemoglobin (Hb) <5 g/dL = severe anemia, Hb 5 to <8 g/dL = moderate anemia, Hb 8 to <11 g/dL = mild anemia, Hb ≥11 g/dL = no anemia). | Day 1 and day 28 - period 1 | 
| Anemia Status Based on Community Screening Campaign 1 (CSC1)/Day 1 in Infants and Children (>6 Months and <5 Years) | Anemia status based on Community Screening Campaign 1 (CSC1)/Day 1 in infants and children (>6 months and <5 years) was measured via hemoglobin levels using the HemoCue® rapid test. This test was performed using a drop of blood collected from the fingertip of each participant. The anemic status is defined as follows: hemoglobin (Hb) <5 g/dL = severe anemia, Hb 5 to <8 g/dL = moderate anemia, Hb 8 to <11 g/dL = mild anemia, Hb ≥11 g/dL = no anemia). | Day 1 (CSC1/day 1) - period 1 | 
| Anemia Status Based on Community Screening Campaign 4 (CSC4)/Day 1 in Infants and Children (>6 Months and <5 Years) | Anemia status based on Community Screening Campaign 4 (CSC4/Day 1) in infants and children (>6 months and <5 years) was measured via hemoglobin levels using the HemoCue® rapid test. This test was performed using a drop of blood collected from the fingertip of each participant. The anemic status is defined as follows: hemoglobin (Hb) <5 g/dL = severe anemia, Hb 5 to <8 g/dL = moderate anemia, Hb 8 to <11 g/dL = mild anemia, Hb ≥11 g/dL = no anemia). | Month 12 (CSC4/day 1) - period 1 | 
| Hemoglobin Level (g/dL) in Community Screening Campaign 1 (CSC1)/Day 1 and CSC4/Day 1 by Study Arm and Age Group (Per Cluster) | Data is presented per cluster. Hemoglobin levels at Community Screening Campaign 1 and 4 (CSC1 and CSC4) on day 1 per age group (5-9 years, 10-14 years, and ≥15 years) in the intervention versus the control arm was measured using the HemoCue® rapid test. This test was performed using a drop of blood collected from the fingertip of each participant. | Day 1 (CSC1/day 1) and month 12 (CSC4/day 1) - period 1 | 
| Percentage of COA566-treated Microscopy-confirmed Asymptomatic Carriers at Community Screening Campaign 1, 2 and 3 (CSC1, CSC2 and CSC3) With Parasitological Cure Rate at Day 7 | Percentage of participants with parasitological cure confirmed via microscopy at day 7 after treatment with COA566. This assessment was done on asymptomatic carriers from Community Screening Campaigns 1, 2 and 3 (CSC1, CSC2 and CSC3) from the intervention group only. | Day 7 of CSC1, CSC2 and CSC3 - period 1 | 
| Percentage of Microscopy-confirmed Gametocyte Carriers Treated With COA566 for Asymptomatic Carriers | Percentage of microscopy-confirmed gametocyte asymptomatic carriers treated with COA566 for asymptomatic carriers in Community Screening Campaign 1, 2 and 3 (CSC1, CSC2 and CSC3). | Day 1, day 7 and day 28 - period 1 | 
| Number of Asymptomatic Carriers With Increase in Hemoglobin Levels by at Least 0.5 g/dL From Community Screening Campaign 1 (CSC1) Infants and Children (>6 Months and <5 Years)- Individual Data | Individual data of number of asymptomatic carriers with increase in hemoglobin levels by at least 0.5 g/dL from Day 1 to Day 28 from Community Screening Campaign 1 (CSC1) infants and children (>6 months and <5 years). Hemoglobin levels were measured using the HemoCue® rapid test. This test was performed with a drop of blood collected from the fingertip at Day 1 and at Day 28. | Day 1 to Day 28- period 1 | 
| Number of Asymptomatic Carriers With Increase in Hemoglobin Levels by at Least 0.5 g/dL From Day 1 to Day 28 of Community Screening Campaign 1 (CSC1) in Infants and Children (>6 Months and <5 Years)- Cluster Data | Data is presented per cluster. Cluster data of number of asymptomatic carriers with increase in hemoglobin levels by at least 0.5 g/dL from Day 1 to Day 28 of Community Screening Campaign 1 (CSC1) in infants and children (>6 months and <5 years) was measured by Hemoglobin levels based on microscopy reading. Mean and Standard Deviation (SD) percent were measured indicating the mean and SD of percentages of cluster frequencies under the study arm for that particular category. | Day 1 to day 28 - period 1 | 
| Number of Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL (SMRC5000) in Asymptomatic Carriers at Any Time of Diagnosis (Per Cluster) | Data is presented per cluster. Number of Symptomatic malaria episode, RDT-confirmed, with parasitemia ≥5000/μL (SMRC5000) in asymptomatic carriers by study arm from all inhabitants diagnosed at any time for asymptomatic carriers. Number of SMRC5000s is measured by Rapid diagnostic test (RDT) and later confirmed to have a parasite density ≥ 5000/uL by microscopy. | 12 months - period 1 | 
| Number of Asymptomatic Carriers With Complicated and Uncomplicated Episodes Combined | Number of asymptomatic carriers diagnosed with 1 Symptomatic malaria episode, RDT-confirmed, with parasitemia ≥5000/μL (SMRC5000), 2 SMRC5000, 3 SMRC5000 and >3 SMRC5000 (complicated and uncomplicated episodes combined). Number of SMRC5000s is measured by Rapid diagnostic test (RDT) and later confirmed to have a parasite density ≥ 5000/uL by microscopy. | 12 months - period 1 | 
| Cumulative Number of Subjects With Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL From Week 1 to Week 50 | Cumulative number of asymptomatic carriers having Symptomatic malaria episode, RDT-confirmed, with parasitemia ≥5000/μL (SMRC5000) from Week 1 to Week 50, was measured from group of participants diagnosed as asymptomatic carriers at Community Screening Campaign (CSC1)/Day1. Number of participants affected before and after diagnosed with ≥1 symptomatic malaria episode, RDT-confirmed, with parasitemia ≥5000/μL (SMRC5000) (complicated and uncomplicated episodes combined). Number of SMRC5000s was detected by Rapid Diagnostic Test (RDT) using a blood sample from each participant and later confirmed to have a parasite density > or = 5000/uL by microscopy. Week (1-2) indicates day1 to day14, week (3-4) indicates day 15 to day 28, week (5-6) indicates day 29 to day 42, etc. After first diagnosis of asymptomatic carriers at CSC1/Day1. | Week 1 to Week 50 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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P. falciparum, malaria, asymptomatic carriers, bed-nets, ITN-insecticide-treated net, idiopathic trigeminal neuralgia, RDT-Rapid diagnostic test