NCT05340153

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.

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 2022

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

April 11, 2022

Completed
Same day until next milestone

Study Start

First participant enrolled

April 11, 2022

Completed
11 days until next milestone

First Posted

Study publicly available on registry

April 22, 2022

Completed
8 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2022

Completed
Last Updated

April 22, 2022

Status Verified

April 1, 2022

Enrollment Period

9 months

First QC Date

April 11, 2022

Last Update Submit

April 15, 2022

Conditions

Keywords

Plasmodium falciparumMalariaArtemether-lumefantrineDihydroartemisinin-piperaquineCameroon

Outcome Measures

Primary Outcomes (1)

  • 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.

    10 months

Secondary Outcomes (4)

  • 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.

    10 months

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

    10 months

  • The number of children with single nucleotide polymorphisms of P. falciparum genes responsible for resistance to AL and DHA-PPQ.

    10 months

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

    10 months

Study Arms (2)

Artemether-lumefantrine

ACTIVE COMPARATOR

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: Artemether-Lumefantrine Drug Combination

Dihydroartemisinin-piperaquine

EXPERIMENTAL

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.

Drug: Dihydroartemisinin-Piperaquine drug combination

Interventions

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.

Also known as: Coartem dispersible
Artemether-lumefantrine

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.

Also known as: D-ARTEPP dispersible
Dihydroartemisinin-piperaquine

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 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.

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, 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

MeSH Terms

Conditions

MalariaMalaria, Falciparum

Interventions

Artemether, 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

Peter Thelma 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 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
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator, Professor of Public Health Biotechnology

Study Record Dates

First Submitted

April 11, 2022

First Posted

April 22, 2022

Study Start

April 11, 2022

Primary Completion

December 31, 2022

Study Completion

December 31, 2022

Last Updated

April 22, 2022

Record last verified: 2022-04

Data Sharing

IPD Sharing
Will share

Research findings will be communicated to 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 2022 for at least 10 years
Access Criteria
Not available for now