Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in two sites in Yemen.

• Register: ANZCTR
• Last refreshed on: 9 August 2022
• Main ID: ACTRN12617000283370
• Date of registration: 23/02/2017
• Prospective Registration: Yes
• Primary sponsor: Ministry of Public Health and Population
• Public title: Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in two sites in Yemen.
• Scientific title: Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in two sites in Yemen.
• Date of first enrolment: 03/12/2019
• Target sample size: 110
• Recruitment status: Completed
• URL: https://anzctr.org.au/ACTRN12617000283370.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Non-randomised trial; Masking: Open (masking not used);Assignment: Single group;Type of endpoint: Safety/efficacy;
• Phase: Phase 4

Countries of recruitment

Yemen

Contacts

• Name: Dr Marian Warsame

• Name: Dr Methaq Abdulla Alssada

Key inclusion & exclusion criteria

Inclusion criteria: 1. age 6 months and above, excluding female minors 12-17 years old and unmarried females aged 18 years and above;
2. mono-infection with P. falciparum detected by microscopy;
3. parasitaemia of 500-200000 per microL asexual forms;
4. presence of axillary temperature greater or equal to 37.5 degrees C 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 the patient or from a parent or guardian in the case of children aged less than 18 years;
8. informed assent from any minor participant aged from 12 to 17 years; and
9. consent for pregnancy testing from female of child-bearing potential and from their parent or guardian if under the age of majority years.

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 6-60 months who has a mid-upper arm circumference < 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);
8. a positive pregnancy test or breastfeeding; and
9. unable to or unwilling to take pregnancy test or to use contraception for married women.


Age minimum: 6 Months
Age maximum: 60 Weeks
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Malaria;
Malaria

Infection - Studies of infection and infectious agents

Intervention(s)

To assess the efficacy and safety of 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 separately. The patient will be given 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 a composite primary outcome.

Enrolled patients will be assessed for parasitological (using microscopy) and clinical responses and treatment outcomes will be classified according to the latest WHO protocol. [At days 1, 2, 3, 7, 14, 21, 28 ]

Secondary Outcome(s)

Percent of adverse event following treatment.
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 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. [At 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). [At day 0 (prior to initiation of the treatment. ]

Secondary ID(s)

None

Source(s) of Monetary Support

Ministry of Public Health and Population

Ethics review

Status: Approved
Approval date: 01/04/2019
Contact:

WHO ERC

Results

• Results available: Yes
• Date Posted: 27/07/2022
• Date Completed: 04/02/2020