Effectiveness and Safety of Artesunate-Amodiaquine and Artemether-Lumefantrine for the Treatment of Malaria in Yaounde
Monitoring the Effectiveness and Safety of Artesunate-Amodiaquine and Artemether-Lumefantrine During the Treatment of Uncomplicated Plasmodium Falciparum Malaria Among Children in Yaounde, Cameroon
1 other identifier
interventional
242
1 country
1
Brief Summary
Artesunate-amodiaquine and artemether-lumfantrine are currently being used for the treatment of uncomplicated Plasmodium falciparum in Cameroon. Globally, many studies have reported high efficacy and safety of artemisinin-based combination therapies (ACTs) mostly under strict supervision of drug intake and limited to children less than 5 years of age. Patients over 5 years of age are usually not involved in such studies. The main objective of this study is to assess the genetic markers of antimalarial drug resistance and drug metabolism subsequent to the efficacy and safety of artesunate-amodiaquine and artemether-lumefantrine during a 28-day follow-up period in children with acute uncomplicated P. falciparum malaria in Yaounde, Cameroon. A randomized, open-labelled, controlled clinical trial comparing artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) will be carried out from 9th May 2019 to 30th November 2020 at two secondary health centres (Cité Verte and Minkoameyos) in Yaounde. 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 informed consents are obtained will be randomized to receive either artesunate-amodiaquine (group A) or artemether-lumefantrine (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-day follow-up period, 92 patients will be enrolled for each of the two study arms. The study will recruit a total of 184 patients. Drug intake will be partially supervised only for the first dose and subsequent doses administered unsupervised as pertains in routine practice in the field. Patients or their parents/guardians will be advised on the time and mode of administration for the 3 days (D0, D1 and D2) treatment unobserved at home. Follow-up visits will be performed on days 3, 7, 14, 21, and 28 to evaluate clinical and parasitological resolution of their malaria episode as well as adverse events. Polymerase chain reaction (PCR) genotyping of merozoite surface proteins 1 and 2 (msp-1, msp-2) as well as glutamate rich protein (GLURP) will be used to differentiate between recrudescence and new infection.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started May 2019
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 9, 2019
CompletedFirst Submitted
Initial submission to the registry
September 17, 2020
CompletedFirst Posted
Study publicly available on registry
September 25, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 30, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
November 30, 2020
CompletedApril 2, 2021
March 1, 2021
1.6 years
September 17, 2020
March 31, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of participants with treatment success and adverse events following treatment with artesunate-modiaquine and artemether-lumefantrine during 28 days follow-up period in children with acute uncomplicated P. falciparum malaria in Yaounde
Eligible children for whom parent/guardian informed consents are obtained will be randomized to receive either artesunate-amodiaquine (group A) or artemether-lumefantrine (group B) and follow-up will be done for a duration of 28 days.
18 months
Secondary Outcomes (4)
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
18 months
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
18 months
Number of children with single nucleotide polymorphisms of P. falciparum genes responsible for AS-AQ and AL resistance
18 months
Number of children haboring single nucleotide polymorphisms in key genes involved in the metabolism of AS-AQ and AL
18 months
Study Arms (2)
Artesunate-amodiaquine (Arm A)
EXPERIMENTALArtesunate-amodiaquine (Coarsucam®: Sanofi-Aventis, France) is co-packaged as artesunate 50 mg and amodiaquine hydrochloride USP equivalent to amodiaquine base of 153.1 mg. Each child shall be given one, two or three tablets depending on the weight.
Artemether-lumefantrine (Arm B)
ACTIVE COMPARATORArtemether-lumefantrine (Coartem®: Novartis, Switzerland) 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 two blisters for each day with one, two or three tablets depending on the weight of the child.
Interventions
Artesunate-amodiaquine (Coarsucam®: Sanofi-Aventis, France) is co-packaged as artesunate 50 mg and amodiaquine hydrochloride USP equivalent to amodiaquine base of 153.1 mg. Each child shall be given one, two or three tablets depending on the weight.
Artemether-lumefantrine (Coartem®: Novartis, Switzerland) 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 two blisters for each day with one, two or three tablets depending on the weight of the child
Eligibility Criteria
You may qualify if:
- Children of either gender, aged 6 months to 120 months will be recruited.
- Acute uncomplicated P. falciparum malaria confirmed by microscopy using Giemsa-stained thick film with an asexual parasite density within the range 1000 to 200000 parasites/μl.
- Presenting with fever (axillary temperature ≥ 37.5oC) 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.
You may not qualify if:
- Mixed 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, hypoglycaemia, 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 breast feed. Persistent vomiting (\>2 episodes within previous 24 hours). Convulsions (\>1 episode within previous 24 hours). Lethargic/unconscious. Severe anaemia (haemoglobin \< 5 g/dl).
- Serious gastrointestinal disease.
- Presence of severe malnutrition defined as a child aged between 6-60 months whose weight-for-high 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 anti-malarial 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 anti-malarial drugs in the last one month.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
District Medical Center Minkoa Meyos
Yaoundé, Center, +237, Cameroon
Related Publications (1)
Niba PTN, Nji AM, Ali IM, Akam LF, Dongmo CH, Chedjou JPK, Fomboh CT, Nana WD, Oben OLA, Selly-Ngaloumo AA, Moyeh MN, Ngu JA, Ludovic AJ, Aboh PM, Ambani MCE, Omgba PAM, Kotcholi GB, Adzemye LM, Nna DRA, Douanla A, Ango Z, Ewane MS, Ticha JT, Tatah FM, Dinza G, Ndikum VN, Fosah DA, Bigoga JD, Alifrangis M, Mbacham WF. Effectiveness and safety of artesunate-amodiaquine versus artemether-lumefantrine for home-based treatment of uncomplicated Plasmodium falciparum malaria among children 6-120 months in Yaounde, Cameroon: a randomized trial. BMC Infect Dis. 2022 Feb 21;22(1):166. doi: 10.1186/s12879-022-07101-2.
PMID: 35189818DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Wilfred Fon Mbacham, PhD
Biotechnology Centre, University of Yaounde I
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
September 17, 2020
First Posted
September 25, 2020
Study Start
May 9, 2019
Primary Completion
November 30, 2020
Study Completion
November 30, 2020
Last Updated
April 2, 2021
Record last verified: 2021-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, CSR
- Time Frame
- 30th November 2020 for at least 10 years
- Access Criteria
- Not available for now
Research findings will be communicated with the scientific community and policymakers. This will be done through public engagements and publications in peer-review journals.