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Efficacy and Safety of Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine in Cameroon

Primary Purpose

Malaria

Status
Not yet recruiting
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Artemether-Lumefantrine Drug Combination
Dihydroartemisinin-Piperaquine drug combination
Sponsored by
University of Yaounde 1
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Malaria focused on measuring Plasmodium falciparum, Malaria, Artemether-lumefantrine, Dihydroartemisinin-piperaquine, Cameroon

Eligibility Criteria

6 Months - 120 Months (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Children of either gender, aged 6 months to 10 years will be recruited.
  • Uncomplicated P. falciparum malaria confirmed by microscopy using Giemsa-stained thick film with an asexual parasite density within the range of 1000 to 200000 parasites/μl.
  • Presenting with fever (axillary temperature ≥ 37.5 ºC) or having a history of fever in the preceding 24 hours.
  • Able to ingest tablets orally (either suspended in water or uncrushed with food).
  • Willing to participate in the study with written informed consent from parent/guardian.
  • Willing and able to attend the clinic on stipulated regular follow-up visits.

Exclusion Criteria:

  • Mixed or mono-infection with another Plasmodium species detected by microscopy.
  • Children who are currently suffering or had the following within the last 2 months: tuberculosis, HIV, schistosomiasis, diabetes mellitus, cardiovascular disease, gout, rheumatoid arthritis, underlying chronic hepatic or renal disease, hypoglycemia, jaundice, respiratory distress, and other inflammatory-related diseases.
  • Signs/symptoms indicating severe/complicated malaria" according to WHO criteria (WHO definition) such as:

    1. Not able to drink or breastfeed.
    2. Persistent vomiting (>2 episodes within the previous 24 hours).
    3. Convulsions (>1 episode within the previous 24 hours).
    4. Lethargic/unconscious.
    5. Severe anemia (hemoglobin < 5 g/dl).
  • Serious gastrointestinal disease.
  • Presence of severe malnutrition defined as a child aged between 6-60 months whose weight-for-height is below -3 z-score (W/H < 70%) or has symmetrical edema involving at least the feet or has a mid-upper arm circumference <115 mm).
  • Regular medication, which may interfere with antimalarial pharmacokinetics.
  • History of hypersensitivity reactions or contraindications to any of the medicine (s) being tested or used as alternative treatment (s).
  • Individuals who have taken part in anti-malarial efficacy and safety studies in the last 3 months.
  • Participants who have taken antimalarial drugs within the last one month.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Experimental

    Arm Label

    Artemether-lumefantrine

    Dihydroartemisinin-piperaquine

    Arm Description

    Drug: Artemether-lumefantrine drug combination Artemether-lumefantrine is formulated as tablets and will be provided in blister packs. Each tablet contains 20 mg artemether and 120 mg lumefantrine. Every pack has a picture showing how the drug should be given and contains a blister of 12 tablets. It will be administered each day as one, two or three tablets depending on the weight of the child.

    Drug: Dihydroartemisinin-piperaquine drug combination Dihydroartemisinin-piperaquine is formulated as tablets and will be provided in blister packs. Each tablet contains 40 mg dihydroartemisinin and 320 mg piperaquine. Every pack has a picture showing how the drug should be given and contains a blister of 6 tablets and given each day as half, one, two or three tablets depending on the weight of the child.

    Outcomes

    Primary Outcome Measures

    The number of participants with treatment success and adverse events following treatment with AL and DHA-PPQ in children infected with uncomplicated P. falciparum malaria.
    Eligible children for whom parent/guardian informed consents are obtained will be randomized to receive either artemether-lumefantrine (group A) or dihydroartemisinin-piperaquine (group B) in the ratio of 1:1.

    Secondary Outcome Measures

    The proportion of patients with early treatment failure, late clinical failure, late parasitological failure or an adequate clinical and parasitological response as indicators of efficacy according to the WHO 2009 guidelines.
    Eligible children for whom parent/guardian informed consents are obtained will be randomized to receive either artemether-lumefantrine (group A) or dihydroartemisinin-piperaquine (group B) in the ratio of 1:1. Recrudescence will be distinguished from re-infection by polymerase chain reaction (PCR) analysis.
    The number of participants with treatment-related adverse events as assessed by CTCAE v4.0.
    Eligible children for whom parent/guardian informed consents are obtained will be randomized to receive either artemether-lumefantrine (group A) or dihydroartemisinin-piperaquine (group B) in the ratio of 1:1.
    The number of children with single nucleotide polymorphisms of P. falciparum genes responsible for resistance to AL and DHA-PPQ.
    Pre-treatment and recrudescence/reinfection samples during follow-up shall be used to characterize the molecular markers of Plasmodium falciparum chloroquine resistant transporter(Pfcrt), Plasmodium falciparum multi-drug resistant 1 (Pfmdr1), and Plasmodium falciparum K13 (Pfk13) propeller domain conferring resistance to artemisinins or partner drugs.
    The number of children with single nucleotide polymorphisms of P. falciparum histidine-rich protein 2 and 3 genes.
    Pre-treatment shall be used to detect single nucleotide polymorphisms present in Plasmodium falciparum histidine-rich protein 2 and 3 genes.

    Full Information

    First Posted
    April 11, 2022
    Last Updated
    April 15, 2022
    Sponsor
    University of Yaounde 1
    Collaborators
    Biotechnology Center (BTC), University of Yaounde I, Cameroon, National Malaria Control Program (NMCP), Cameroon, Association Camerounaise pour le Marketing Social (ACMS), Cameroon, Impact Malaria, Cameroon
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05340153
    Brief Title
    Efficacy and Safety of Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine in Cameroon
    Official Title
    Efficacy and Safety of Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Plasmodium Falciparum Malaria Among Children in the North Region of Cameroon
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    April 11, 2022 (Anticipated)
    Primary Completion Date
    December 31, 2022 (Anticipated)
    Study Completion Date
    December 31, 2022 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    University of Yaounde 1
    Collaborators
    Biotechnology Center (BTC), University of Yaounde I, Cameroon, National Malaria Control Program (NMCP), Cameroon, Association Camerounaise pour le Marketing Social (ACMS), Cameroon, Impact Malaria, Cameroon

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    Malaria is an infectious disease transmitted by the bite of an infected female anopheles mosquito. The most vulnerable group that bears the highest disease burden includes children less than five years and pregnant women. Artemether-lumefantrine (AL) has been used for the treatment of uncomplicated Plasmodium falciparum in Cameroon since 2006. In 2020, the government of Cameroon also adopted the use of dihydroartemisinin-piperaquine (DHA-PPQ) as one of the first line drugs for the treatment of malaria. Globally, several studies among children have reported high efficacy and safety of artemisinin-based combination therapies (ACTs). However, there is paucity of data to support the continuous use of AL and DHA-PPQ in Cameroon. The main objective of this study is to assess the efficacy and safety of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA-PPQ) uncomplicated P. falciparum malaria in the North Region of Cameroon. A randomized, open-label, controlled clinical trial comparing artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA-PPQ) will be carried out from 11th April to 31st December, 2022 at two hospitals in the North Region of Cameroon. The study participants shall include febrile patients aged 6 months to 10 years with confirmed uncomplicated P. falciparum infection. Eligible children for whom parent/guardian assents are obtained will be randomized to receive either artemether-lumefantrine (group A) or dihydroartemisinin-piperaquine (group B) in the ratio 1:1. A minimum sample of 76 patients will be required for the study. With a 20 % increase to allow loss to follow-up and withdrawals during the 28-days (AL) or 42-days (DHA-PPQ) follow-up period, 92 patients will be enrolled into each of the two study arms. The study will recruit a total of 184 patients. However, since 2 study sites will be involved, a minimum of 92 (46 per drug arm) participants shall be enrolled per site. Drug intake will be done under strict supervision on days 0, 1 and 2. Follow-up visits will be performed on days 3, 7, 14, 21, 28, 35 and 42 to evaluate clinical and parasitological resolution of their malaria episode as well as adverse events. Polymerase chain reaction (PCR) of Plasmodium falciparum merozoite surface proteins 1 and 2 (Pfmsp1, Pfmsp2), glutamate-rich protein (Pfglurp) and microsatellites will be used to differentiate between recrudescence and new infection.
    Detailed Description
    Brief title: Efficacy and Safety of Artemether-Lumefantrine (AL) and Dihydroartemisinin-Piperaquine (DHA-PPQ) in Cameroon Official title: Efficacy and Safety of Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria among children in the North Region of Cameroon Purpose: To assess the efficacy and safety of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA-PPQ) for the treatment of uncomplicated P. falciparum malaria among children 6 to 120 months at District Hospital Figuil and District Hospital Guider in the North Region of Cameroon. Background: Malaria is an infectious disease transmitted by the bite of an infected female anopheles mosquito. The most vulnerable group includes children less than five years and pregnant women. artemether-lumefantrine (AL) has been used for the treatment of uncomplicated Plasmodium falciparum in Cameroon since 2006. In 2020, the government of Cameroon also adopted the use of dihydroartemisinin-piperaquine (DHA-PPQ) as one of the first line drugs for the treatment of malaria. Globally, several studies among children have reported high efficacy and safety of artemisinin-based combination therapies (ACTs). However, there is paucity of data to support the continuous use of AL and DHA-PPQ in Cameroon. Objective: To assess the efficacy and safety of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA-PPQ) for the treatment of uncomplicated P. falciparum malaria among children 6 to 120 months at District Hospital Figuil and District Hospital Guider in the North Region of Cameroon. Study sites: District Hospital Guider and District Hospital Figuil in the North Region of Cameroon. Study period: 11th April to 31st December 2022. Study design: This surveillance study is a two-arm, open-label, randomized controlled clinical trial. Patient population: Febrile patients aged 6 months to 10 years, with confirmed uncomplicated P. falciparum infection. Eligible children for whom parent/guardian informed consents are obtained will be randomized to receive either artemether-lumefantrine (group A) or dihydroartemisinin-piperaquine (group B) in the ratio 1:1. Sample size: A minimum sample of 76 patients will be required for the study. With a 20 % increase to allow for loss to follow-up and withdrawals during the 28-days and 42-days follow-up period, 92 patients will be enrolled for each of the two study arms. The study will recruit a total of 184 patients. At least 46 participants shall be enrolled into each drug arm of at the two sites. Treatment (s) and follow-up: Drug intake will be done under strict supervision on days 0, 1 and 2. Follow-up visits will be performed on days 3, 7, 14, 21, 28 (AL), 35 and 42 (DHA-PPQ) to evaluate clinical and parasitological resolution of their malaria episode as well as adverse events. Polymerase chain reaction (PCR) of Plasmodium falciparum merozoite surface proteins 1 and 2 (Pfmsp1, Pfmsp2), glutamate-rich protein (Pfglurp) and microsatellites will be used to differentiate between recrudescence and new infection. Classification of treatment outcomes: Classification of treatment outcomes will be done based on the WHO 2009 guidelines: treatment failure (Early Treatment Failure-ETF, Late Clinical failure-LCF and Late Parasitological Failure-LPF) and treatment success (Adequate Clinical and Parasitological Response-ACPR).

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Malaria
    Keywords
    Plasmodium falciparum, Malaria, Artemether-lumefantrine, Dihydroartemisinin-piperaquine, Cameroon

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 4
    Interventional Study Model
    Parallel Assignment
    Model Description
    Eligible children for whom parent/guardian authorization and assent are obtained will be randomized to receive either artemether-lumefantrine (group A) or dihydroartemisinin-piperaquine (group B) in the ratio 1:1
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    184 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Artemether-lumefantrine
    Arm Type
    Active Comparator
    Arm Description
    Drug: Artemether-lumefantrine drug combination Artemether-lumefantrine is formulated as tablets and will be provided in blister packs. Each tablet contains 20 mg artemether and 120 mg lumefantrine. Every pack has a picture showing how the drug should be given and contains a blister of 12 tablets. It will be administered each day as one, two or three tablets depending on the weight of the child.
    Arm Title
    Dihydroartemisinin-piperaquine
    Arm Type
    Experimental
    Arm Description
    Drug: Dihydroartemisinin-piperaquine drug combination Dihydroartemisinin-piperaquine is formulated as tablets and will be provided in blister packs. Each tablet contains 40 mg dihydroartemisinin and 320 mg piperaquine. Every pack has a picture showing how the drug should be given and contains a blister of 6 tablets and given each day as half, one, two or three tablets depending on the weight of the child.
    Intervention Type
    Drug
    Intervention Name(s)
    Artemether-Lumefantrine Drug Combination
    Other Intervention Name(s)
    Coartem dispersible
    Intervention Description
    Artemether-lumefantrine is formulated as tablets and will be provided in blister packs. Each tablet contains 20 mg artemether and 120 mg lumefantrine. Every pack has a picture showing how the drug should be given and contains 1 blister of 12 tablets. It will be administered each day as two, four, six or eight tablets depending on the weight of the child.
    Intervention Type
    Drug
    Intervention Name(s)
    Dihydroartemisinin-Piperaquine drug combination
    Other Intervention Name(s)
    D-ARTEPP dispersible
    Intervention Description
    Dihydroartemisinin-piperaquine is a formulated as tablets and will be provided in blister packs. Each tablet contains 40 mg dihydroartemisinin and 320 mg piperaquine. Every pack has a picture showing how the drug should be given and contains 1 blister of 6 tablets. It will be given each day as a half, one, two or three tablets depending on the weight of the child.
    Primary Outcome Measure Information:
    Title
    The number of participants with treatment success and adverse events following treatment with AL and DHA-PPQ in children infected with uncomplicated P. falciparum malaria.
    Description
    Eligible children for whom parent/guardian informed consents are obtained will be randomized to receive either artemether-lumefantrine (group A) or dihydroartemisinin-piperaquine (group B) in the ratio of 1:1.
    Time Frame
    10 months
    Secondary Outcome Measure Information:
    Title
    The proportion of patients with early treatment failure, late clinical failure, late parasitological failure or an adequate clinical and parasitological response as indicators of efficacy according to the WHO 2009 guidelines.
    Description
    Eligible children for whom parent/guardian informed consents are obtained will be randomized to receive either artemether-lumefantrine (group A) or dihydroartemisinin-piperaquine (group B) in the ratio of 1:1. Recrudescence will be distinguished from re-infection by polymerase chain reaction (PCR) analysis.
    Time Frame
    10 months
    Title
    The number of participants with treatment-related adverse events as assessed by CTCAE v4.0.
    Description
    Eligible children for whom parent/guardian informed consents are obtained will be randomized to receive either artemether-lumefantrine (group A) or dihydroartemisinin-piperaquine (group B) in the ratio of 1:1.
    Time Frame
    10 months
    Title
    The number of children with single nucleotide polymorphisms of P. falciparum genes responsible for resistance to AL and DHA-PPQ.
    Description
    Pre-treatment and recrudescence/reinfection samples during follow-up shall be used to characterize the molecular markers of Plasmodium falciparum chloroquine resistant transporter(Pfcrt), Plasmodium falciparum multi-drug resistant 1 (Pfmdr1), and Plasmodium falciparum K13 (Pfk13) propeller domain conferring resistance to artemisinins or partner drugs.
    Time Frame
    10 months
    Title
    The number of children with single nucleotide polymorphisms of P. falciparum histidine-rich protein 2 and 3 genes.
    Description
    Pre-treatment shall be used to detect single nucleotide polymorphisms present in Plasmodium falciparum histidine-rich protein 2 and 3 genes.
    Time Frame
    10 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    6 Months
    Maximum Age & Unit of Time
    120 Months
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Children of either gender, aged 6 months to 10 years will be recruited. Uncomplicated P. falciparum malaria confirmed by microscopy using Giemsa-stained thick film with an asexual parasite density within the range of 1000 to 200000 parasites/μl. Presenting with fever (axillary temperature ≥ 37.5 ºC) or having a history of fever in the preceding 24 hours. Able to ingest tablets orally (either suspended in water or uncrushed with food). Willing to participate in the study with written informed consent from parent/guardian. Willing and able to attend the clinic on stipulated regular follow-up visits. Exclusion Criteria: Mixed or mono-infection with another Plasmodium species detected by microscopy. Children who are currently suffering or had the following within the last 2 months: tuberculosis, HIV, schistosomiasis, diabetes mellitus, cardiovascular disease, gout, rheumatoid arthritis, underlying chronic hepatic or renal disease, hypoglycemia, jaundice, respiratory distress, and other inflammatory-related diseases. Signs/symptoms indicating severe/complicated malaria" according to WHO criteria (WHO definition) such as: Not able to drink or breastfeed. Persistent vomiting (>2 episodes within the previous 24 hours). Convulsions (>1 episode within the previous 24 hours). Lethargic/unconscious. Severe anemia (hemoglobin < 5 g/dl). Serious gastrointestinal disease. Presence of severe malnutrition defined as a child aged between 6-60 months whose weight-for-height is below -3 z-score (W/H < 70%) or has symmetrical edema involving at least the feet or has a mid-upper arm circumference <115 mm). Regular medication, which may interfere with antimalarial pharmacokinetics. History of hypersensitivity reactions or contraindications to any of the medicine (s) being tested or used as alternative treatment (s). Individuals who have taken part in anti-malarial efficacy and safety studies in the last 3 months. Participants who have taken antimalarial drugs within the last one month.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Wilfred Fon Mbacham, PhD
    Phone
    (+237) 677579180
    Email
    wfmbacham@yahoo.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Peter Thelma Ngwa Niba, MSc
    Phone
    (+237) 653254729
    Email
    thelma2009@yahoo.co.uk
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Wilfred Fon Mbacham, PhD
    Organizational Affiliation
    University of Yaounde I
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    Research findings will be communicated to the scientific community and policymakers. This will be done through public engagements and publications in peer-review journals.
    IPD Sharing Time Frame
    31st December 2022 for at least 10 years
    IPD Sharing Access Criteria
    Not available for now

    Learn more about this trial

    Efficacy and Safety of Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine in Cameroon

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