NCT04829695

Brief Summary

Malaria remains a major public health concern in Cameroon especially among vulnerable groups such as children less than five years and pregnant women. Artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) have been used for the treatment of uncomplicated Plasmodium falciparum in Cameroon since 2004. Worldwide, several studies among children have reported high efficacy and safety of artemisinin-based combination therapies (ACTs). There is paucity of data to support the continuous use of ASAQ and AL in Cameroon. The main objective of this study is to assess 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 the Center Region of Cameroon. A randomized, open-labelled, controlled clinical trial comparing artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) will be carried out from 5th April to 31st December, 2021 at six hospitals in the Center 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 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. However, since 6 sites will be involved, a minimum of 30 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, 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

35
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
184

participants targeted

Target at P50-P75 for phase_4

Timeline
Completed

Started Apr 2021

Shorter than P25 for phase_4

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 31, 2021

Completed
2 days until next milestone

First Posted

Study publicly available on registry

April 2, 2021

Completed
3 days until next milestone

Study Start

First participant enrolled

April 5, 2021

Completed
9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2021

Completed
Last Updated

April 2, 2021

Status Verified

March 1, 2021

Enrollment Period

9 months

First QC Date

March 31, 2021

Last Update Submit

March 31, 2021

Conditions

Keywords

MalariaPlasmodium falciparumArtesunate-amodiaquineArtemether-lumefantrine

Outcome Measures

Primary Outcomes (1)

  • Number of participants with treatment success and adverse events following treatment with ASAQ and AL during 28 days follow-up period in children with uncomplicated P. falciparum malaria

    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.

    10 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

    10 months

  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    10 months

  • Number of children with single nucleotide polymorphisms of P. falciparum genes responsible for resistance to ASAQ and AL

    10 months

  • Number of children with single nucleotide polymorphisms of P. falciparum histidine-rich protein 2 and 3 genes

    10 months

Study Arms (2)

Artesunate-amodiaquine (Arm A)

EXPERIMENTAL

Artesunate-amodiaquine 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.

Drug: Artesunate-amodiaquine drug combination

Artemether-lumefantrine (Arm B)

ACTIVE COMPARATOR

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 two blisters for each day with one, two or three tablets depending on the weight of the child.

Drug: Artemether-lumefantrine drug combination

Interventions

Artesunate-amodiaquine 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.

Also known as: Coarsucam
Artesunate-amodiaquine (Arm A)

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 two blisters for each day with one, two or three tablets depending on the weight of the child.

Also known as: Coartem
Artemether-lumefantrine (Arm B)

Eligibility Criteria

Age6 Months - 120 Months
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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 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 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, 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 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 oedema 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 within the last one month.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

MeSH Terms

Conditions

Malaria, FalciparumMalaria

Interventions

amodiaquine, artesunate drug combinationArtemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

Protozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne Diseases

Intervention Hierarchy (Ancestors)

ArtemetherArtemisininsReactive Oxygen SpeciesFree RadicalsInorganic ChemicalsOrganic ChemicalsLumefantrineFluorenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsSesquiterpenesTerpenesPolycyclic CompoundsDrug CombinationsPharmaceutical Preparations

Study Officials

  • Wilfred Fon Mbacham, PhD

    University of Yaounde I

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Wilfred Fon Mbacham, PhD

CONTACT

PeterThelma Ngwa Niba, MSc

CONTACT

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Eligible children for whom parent/guardian informed consent are obtained will be randomized to receive either artesunate-amodiaquine (group A) or artemether-lumefantrine (group B) in the ratio 1:1.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor Wilfred Fon Mbacham

Study Record Dates

First Submitted

March 31, 2021

First Posted

April 2, 2021

Study Start

April 5, 2021

Primary Completion

December 31, 2021

Study Completion

December 31, 2021

Last Updated

April 2, 2021

Record last verified: 2021-03

Data Sharing

IPD Sharing
Will share

Research findings will be communicated with the scientific community and policymakers. This will be done through public engagements and publications in peer-review journals.

Shared Documents
STUDY PROTOCOL, CSR
Time Frame
31st December 2021 for at least 10 years
Access Criteria
Not available for now