Effectiveness and Safety of Artesunate-Amodiaquine and Artemether-Lumefantrine for the Treatment of Malaria in Yaounde

• Status: Completed
• Trial end date: 2020-11-30
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Yaounde 1
• Collaborators: Developing Excellence in Leadership, Training and Science Africa Initiative; Malaria Research Capacity Development in West and Central Africa Consortium; United Kingdom Department for International Development; Wellcome Trust United Kingdom
• Treatments: Amodiaquine; Amodiaquine, artesunate drug combination; Artemether; Artemether, Lumefantrine Drug Combination; Artesunate; Lumefantrine

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.