Efficacy and safety of Artesunate+Amodiaquine and Artemether+Lumefatrine for the treatment of uncomplicated Plasmodium falciparum malaria in children in Saclepea-Mahn Comprehensive Health Center (Saclepea-Mahn District, Nimba County), Rennie Hospital (Kakata District, Margibi County) and Sinje Health Center (Garwula District, Cape Mount County and Bensonville Hospital-Montserrado County) in Liberia

• Register: ANZCTR
• Last refreshed on: 11 November 2019
• Main ID: ACTRN12617001064392
• Date of registration: 21/07/2017
• Prospective Registration: Yes
• Primary sponsor: Ministry of Health of Liberia
• Public title: Efficacy and safety of Artesunate+Amodiaquine and Artemether+Lumefatrine for the treatment of uncomplicated Plasmodium falciparum malaria in children in Saclepea-Mahn Comprehensive Health Center (Saclepea-Mahn District, Nimba County), Rennie Hospital (Kakata District, Margibi County) and Sinje Health Center (Garwula District, Cape Mount County and Bensonville Hospital-Montserrado County) in Liberia
• Scientific title: Efficacy and safety of Artesunate+Amodiaquine and Artemether+Lumefatrine for the treatment of uncomplicated Plasmodium falciparum in children malaria in Saclepea-Mahn Comprehensive Health Center (Saclepea-Mahn District, Nimba County), Rennie Hospital (Kakata District, Margibi County) and Sinje Health Center (Garwula District, Cape Mount County and Bensonville Hospital-Montserrado County) in Liberia
• Date of first enrolment: 19/12/2017
• Target sample size: 528
• Recruitment status: Completed
• URL: https://anzctr.org.au/ACTRN12617001064392.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Non-randomised trial; Masking: Open (masking not used);Assignment: Other;Type of endpoint: Safety/efficacy;
• Phase: Phase 4

Countries of recruitment

Liberia

Contacts

• Name: Dr Benjamin Vonhm

• Name: Dr Benjamin Vonhm

Key inclusion & exclusion criteria

Inclusion criteria: 1. age 6-59 months;
2. mono-infection with P. falciparum detected by microscopy;
3. parasitaemia of 2000–200000/µl asexual forms;
4. presence of axillary or tympanic temperature greater or equal to 37.5 degree centigrade or history of fever during the past 24 h
5. ability to swallow oral medication;
6. ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule;
7. informed consent from a parent or guardian of children aged 6-59 months;
8. Patients living within 5 km radius of the health facility

Exclusion criteria: 1. Presence of general danger signs in children aged under 5 years or signs of severe falciparum malaria according to the definitions of WHO;
2. Weight under 5 kg;
3. Mixed or mono-infection with another Plasmodium species detected by microscopy;
4. Presence of severe malnutrition defined as a child aged 6-59 months whose mid-upper arm circumference less than 115 mm);
5. Presence of febrile conditions due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases, HIV/AIDS);
6. Regular medication, which may interfere with antimalarial pharmacokinetics;
7. History of hypersensitivity reactions or contraindications to any of the medicine(s) being tested or used as alternative treatment(s).


Age minimum: 6 Months
Age maximum: 59 Months
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Malaria;
Malaria

Infection - Studies of infection and infectious agents

Intervention(s)

The aim of the study is to evaluates the efficacy and safety of artesunate+amodiaquine and artemether+lumefantrine with the following dosages:
Artesunate-amodiaquine: 4 mg/kg artesunate + 10mg/kg amodiaquine once daily for 3 consecutive days will be given.
Artemether-lumefantrine containing 20 mg artemether+ 120 mg lumefantrine in each tablet will be given twice daily for three days according to the recommended weight bands as follows: 1 tablet to those weighing 5 to 14 kg; 2 tablets for 15 to 24 kg; 3 tablets for 25 to 34 kg and 4 tablets for equal or greater than 35 kg. The total target dose ranges are 5-24 mg/kg bw of artemether and 29-144 mg/kg bw of lumefantrine.

All treatments will be taken orally under direct supervision by the health worker. The two drugs will be tested sequentially. The patient will be given artesunate+amodiaquine or artemether+lumefantrine and will be followed up for 28 days.

Primary Outcome(s)

Percent of treatment failures (early treatment failure + late clinical failure +late parasitological failure). This is composite primary outcome.

Enrolled patients will be assessed for parasitological and clinical responses during the 28 days follow-up and treatment outcomes will be classified according to the latest WHO protocol. [On days 0,1,2,3,7,14,21 and 28]

Secondary Outcome(s)

Percent of adverse event following treatment of each drugs will be documented.
The known adverse events of:
Artesunate+amodiaquine are abdominal pain, asthenia, cough, diarrhoea, dizziness, insomnia, loss of appetite, nausea, vomiting.
Atemether+lumefantrine are abdominal pain, asthenia, cough, diarrhoea, dizziness, fever, headache, joint and muscle pain, loss of appetite, rush, nausea, vomiting.

Parents or guardians of all enrolled children will be asked on each visit routinely about previous symptoms and about symptoms that have emerged since the previous follow-up visit. When clinically indicated, patients will be evaluated and treated appropriately. All adverse events will be recorded on the case report form.[Days 1, 2, 3, 7, 14, 21, 28 ]

Prevalence of artemisinin resistance molecular markers (K13).

Parasite DNA extracted from the dried blood spots will be analyzed by PCR and sequencing for the presence of K13 (molecular marker for artemisinin resistance). [On day 0 (prior to treatment)]

Secondary ID(s)

None

Source(s) of Monetary Support

Ministry of Health of Liberia

Ethics review

Status: Approved
Approval date:
Contact:

WHO ERC