Clinical trial NCT04829695: Efficacy and Safety of Artesunate-amodiaquine and Artemether-lumefantrine for the Treatment of Malaria in Cameroon
Official title: Efficacy and Safety of Artesunate-amodiaquine (ASAQ) and Artemether-lumefantrine (AL) for the Treatment of Uncomplicated Plasmodium Falciparum Malaria in the Center Region of Cameroon
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Falciparum Malaria
Keywords: Malaria
Plasmodium falciparum
Artesunate-amodiaquine
Artemether-lumefantrine
Lead sponsor: University of Yaounde 1
Sponsor class: OTHER
Collaborators: name: Biotechnology Center (BTC), University of Yaounde I, Cameroon
name: National Malaria Control Program (NMCP), Cameroon
name: Impact Malaria, Cameroon
name: Association Camerounaise pour le Marketing Social (ACMS), Cameroon
First posted: 2021-04-02
Enrollment: 184
Sex: ALL
Minimum age (years): 6
Maximum age (years): 120
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

Detailed description: Brief title: Efficacy and safety of artesunate-amodiaquine and artemether-lumefantrine for the treatment of malaria in Cameroon.

Official title: Monitoring the efficacy and safety of artesunate-amodiaquine and artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria among children in the Center Region of Cameroon.

Purpose: To monitor the efficacy and safety of artesunate-amodiaquine and artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria among children in the Center Region of Cameroon.

Background: Malaria remains a major public health concern in Cameroon especially among vulnerable groups such as children less than 5 years and pregnant women. artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) are currently being used for the treatment of uncomplicated Plasmodium falciparum in Cameroon. 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.

Objective: To assess the efficacy and safety of artesunate-amodiaquine and artemether-lumefantrine during a 28-day follow-up period among children with acute uncomplicated P. falciparum malaria in Center Region of Cameroon.

Study sites: District Hospital Akonolinga, District Hospital Mfou, District Hospital Soa, District Hospital Mbalmayo, District Hospital Mbandjock, and District Hospital Ngog-Mapubi in the Center Region of Cameroon.

Study period: 5th April to 31st December, 2021. 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 artesunate-amodiaquine (group A) or artemether-lumefantrine (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 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. At least 30 participants shall be enrolled at each of the six study 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, 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.

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).

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 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.

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, hypoglycaemia, 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 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.

Primary outcomes:
measure: 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
timeFrame: 10 months
Secondary outcomes:
measure: 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
timeFrame: 10 months
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: 10 months
measure: Number of children with single nucleotide polymorphisms of P. falciparum genes responsible for resistance to ASAQ and AL
timeFrame: 10 months
measure: Number of children with single nucleotide polymorphisms of P. falciparum histidine-rich protein 2 and 3 genes
timeFrame: 10 months
Other outcomes:
Locations:
Study officials:
affiliation: University of Yaounde I
name: Wilfred Fon Mbacham, PhD
role: PRINCIPAL_INVESTIGATOR
References: