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

Primary Purpose

Malaria

Status

Completed

Phase

Phase 4

Locations

Burkina Faso

Study Type

Interventional

Intervention

COA566

About this trial

This is an interventional treatment trial for Malaria focused on measuring P. falciparum, malaria, asymptomatic carriers, bed-nets, ITN-insecticide-treated net, idiopathic trigeminal neuralgia, RDT-Rapid diagnostic test

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Novartis Investigative Site
Centre National de Recherche et de Formation sur le Paludisme
Novartis Investigative site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Intervention

Control

Arm Description

Participants received COA566 treatment for asymptomatic carriage of P. falciparum and for symptomatic malaria episodes.

Participants received COA566 treatment for symptomatic malaria episodes only.

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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).

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).

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.

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.

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).

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT01256658

First Posted

December 6, 2010

Last Updated

January 14, 2014

Sponsor

Novartis

1. Study Identification

Unique Protocol Identification Number

NCT01256658

Brief Title

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

Official Title

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)

Study Type

Interventional

2. Study Status

Record Verification Date

November 2013

Overall Recruitment Status

Completed

Study Start Date

November 2010 (undefined)

Primary Completion Date

July 2012 (Actual)

Study Completion Date

July 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Malaria

Keywords

P. falciparum, malaria, asymptomatic carriers, bed-nets, ITN-insecticide-treated net, idiopathic trigeminal neuralgia, RDT-Rapid diagnostic test

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

14075 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Intervention

Arm Type

Experimental

Arm Description

Participants received COA566 treatment for asymptomatic carriage of P. falciparum and for symptomatic malaria episodes.

Arm Title

Control

Arm Type

Experimental

Arm Description

Participants received COA566 treatment for symptomatic malaria episodes only.

Intervention Type

Drug

Intervention Name(s)

COA566

Other Intervention Name(s)

Artemether-lumefantrine

Intervention Description

COA566 tablets or dispersible tablets twice daily during 3 days; dosage according to body weight.

Primary Outcome Measure Information:

Title

Description

Time Frame

Month 12 of period 1

Title

Change in Hemoglobin Level (g/dL) in Asymptomatic Carriers >6 Months of Age (Per Cluster)

Description

Time Frame

Day 1 and day 28 of period 1

Secondary Outcome Measure Information:

Title

Microscopy-confirmed Gametocyte Carriers at Community Screening Campaign 4 (CSC4) (Per Cluster)

Description

Time Frame

Month 12 - period 1

Title

Microscopy Confirmed Asymptomatic Carriers of P. Falciparum at Community Screening Campaign 4 (CSC4) (Per Cluster)

Description

Time Frame

Month 12 - period 1

Title

Change in Hemoglobin Level (g/dL) From Community Screening Campaign 1(CSC1)/Day 1 to Community Screening Campaign 4 (CSC4)/Day 1 (Per Cluster)

Description

Time Frame

Day 1 (CSC1/day 1) and month 12 (CSC4/day 1) - period 1

Title

Number of Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL (SMRC5000s) Per Person-year in Post Community Screening Campaign (CSC)

Description

Time Frame

12 months - period 1

Title

Number of Participants With Hospitalizations, Severe Malaria Episodes or Death Post Community Screening Campaign (CSC)

Description

Total number of participants (all ages) with hospitalizations, severe malaria episodes or death after Community Screening Campaign (CSC) was assessed.

Time Frame

12 months - period 1

Title

Number of Participants (Infants and Children (> 6 Months and < 5 Years)) With Hospitalizations, Severe Malaria Episodes or Death Post Community Screening Campaign (CSC)

Description

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.

Time Frame

12 months - period 1

Title

Mean of Microscopy-confirmed Asymptomatic Carriers From Community Screening Campaigns 1, 2, 3 and 4 (CSC1, CSC2, CSC3 and CSC4) (Per Cluster)

Description

Time Frame

12 months - period 1

Title

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)

Description

Time Frame

12 months - period 1

Title

Number of Microscopy and qRT-PCR-confirmed Gametocyte Carriers at Community Screening Campaign 4 (CSC4)

Description

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.

Time Frame

Month 12 (CSC4/day 1) - period 1

Title

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

Description

Time Frame

Day 1 and day 28 - period 1

Title

Anemia Status Based on Community Screening Campaign 1 (CSC1)/Day 1 in Infants and Children (>6 Months and <5 Years)

Description

Time Frame

Day 1 (CSC1/day 1) - period 1

Title

Anemia Status Based on Community Screening Campaign 4 (CSC4)/Day 1 in Infants and Children (>6 Months and <5 Years)

Description

Time Frame

Month 12 (CSC4/day 1) - period 1

Title

Hemoglobin Level (g/dL) in Community Screening Campaign 1 (CSC1)/Day 1 and CSC4/Day 1 by Study Arm and Age Group (Per Cluster)

Description

Time Frame

Day 1 (CSC1/day 1) and month 12 (CSC4/day 1) - period 1

Title

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

Description

Time Frame

Day 7 of CSC1, CSC2 and CSC3 - period 1

Title

Percentage of Microscopy-confirmed Gametocyte Carriers Treated With COA566 for Asymptomatic Carriers

Description

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).

Time Frame

Day 1, day 7 and day 28 - period 1

Title

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

Description

Time Frame

Day 1 to Day 28- period 1

Title

Description

Time Frame

Day 1 to day 28 - period 1

Title

Number of Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL (SMRC5000) in Asymptomatic Carriers at Any Time of Diagnosis (Per Cluster)

Description

Time Frame

12 months - period 1

Title

Number of Asymptomatic Carriers With Complicated and Uncomplicated Episodes Combined

Description

Time Frame

12 months - period 1

Title

Cumulative Number of Subjects With Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL From Week 1 to Week 50

Description

Time Frame

Week 1 to Week 50

10. Eligibility

Sex

All

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Burkina Faso

ZIP/Postal Code

2208

Country

Burkina Faso

Facility Name

Centre National de Recherche et de Formation sur le Paludisme

City

Ouagadougou

Country

Burkina Faso

Facility Name

Novartis Investigative site

City

Ouagadougou

Country

Burkina Faso

12. IPD Sharing Statement

Citations:

PubMed Identifier

20096111

Citation

Ogutu B, Tiono AB, Makanga M, Premji Z, Gbadoe AD, Ubben D, Marrast AC, Gaye O. Treatment of asymptomatic carriers with artemether-lumefantrine: an opportunity to reduce the burden of malaria? Malar J. 2010 Jan 22;9:30. doi: 10.1186/1475-2875-9-30.

Results Reference

background

PubMed Identifier

24215306

Citation

Tiono AB, Guelbeogo MW, Sagnon NF, Nebie I, Sirima SB, Mukhopadhyay A, Hamed K. Dynamics of malaria transmission and susceptibility to clinical malaria episodes following treatment of Plasmodium falciparum asymptomatic carriers: results of a cluster-randomized study of community-wide screening and treatment, and a parallel entomology study. BMC Infect Dis. 2013 Nov 12;13:535. doi: 10.1186/1471-2334-13-535.

Results Reference

derived

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

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