Efficacy and safety of artemether-lumefantrine, artesunate-amodiaquine and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in three provinces in Angola

• Register: ANZCTR
• Last refreshed on: 13 January 2020
• Main ID: ACTRN12615000107527
• Date of registration: 05/02/2015
• Prospective Registration: Yes
• Primary sponsor: Ministry of Health
• Public title: Efficacy and safety of artemether-lumefantrine, artesunate-amodiaquine and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in three provinces in Angola
• Scientific title: Efficacy and safety of artemether-lumefantrine, artesunate-amodiaquine and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in three provinces in Angola
• Date of first enrolment: 02/03/2015
• Target sample size: 600
• Recruitment status: Not yet recruiting
• URL: https://anzctr.org.au/ACTRN12615000107527.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: Not Applicable

Countries of recruitment

Angola

Contacts

• Name: Dr Mateusz Plucinski

• Name: Dr Mateusz Plucinski

Key inclusion & exclusion criteria

Inclusion criteria: 1. age between 6 months to 9 years;
2. weight greater than or equal to 5 kg;
3. mono-infection with P. falciparum detected by microscopy;
4. parasitaemia of 2000 - 100000 asexual forms per microliter;
5. presence of axillary or tympanic temperature greater than or equal to 37.5 degree centigrade or history of fever during the past 24 h;
6. hemoglobin greater than 5.0g/dl;
7. ability to swallow oral medication;
8. easy access to the health facility and ability/willingness to return to the health facility over the course of the four weeks (six weeks for DP) of follow-up;
9. informed consent from the parent or guardian.

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. pneumonia or bronchopneumonia;
3. history of taking antimalarials (or antibiotics with antimalarial activity such as cotrimoxazol, tetracycline or doxycycline) in the last 14 days;
4. mixed or mono-infection with another Plasmodium species detected by microscopy;
5. presence of severe malnutrition defined as a child aged 6-60 months whose weight-for-height is below –3 z-score
6. 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);
7. regular medication, which may interfere with antimalarial pharmacokinetics;
8. 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: 9 Years
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 (i) artemether/lumefantrine (20 mg of artemether and 120 mg of
lumefantrine in a tablet) with dose regimen (one tablet to those weighing 5-14kg; two tablets for 15-24 kg; three tablets for 25-34 kg and four tablets for greater than or equal to 35 kg); (ii) artesunate+amodiaquine with dose regimen(4.5-8.9 kg:1 tablet of 25 mg AS/67.5 mg AQ), 9-17.9 kg: 1 tablet 50 mg AS/135 mg AQ, 18-35.9kg: 1 tablet 100 mg AS/270 mg AQ, greater than or equal to 36 kg: 2 tablets 100 mg AS/270 mg AQ);and (iii) dihydroartemisinin-piperaquine (40mg/320mg) with dose regimen of for the treatment of 5-9.9 kg: 0.5 tablet, 10-19.9 kg:1 tablet, 20-39.9 kg: 2 tablets, greater than or equal to 40 Kg: 3 tablets) for uncomplicated P. falciparum infection. The treatment will be taken orally. Eligibile subjects
will be treated for three days (daily dose for
artesunate+amodiaquine and dihydroartemisinin and twice daily dose for artemether lumefantrine).

All treatment was given under observation of the health worker who is administering the drug.

Primary Outcome(s)

Dihydroartemisinin+piperaquine:
Percent of treatment failures (early treatment failure + late clinical failure + late parasitological failure) for dihydroartemisinin+piperaquine. It is composite primary outcome.

Enrolled patients will be assessed for parasitological (using microscopy), clinical responses during the 42 days and treatment outcomes will be classified according to the latest WHO protocol.[At day 42 following initiation of dihydroartemisinin+piperaquine treatment. ]

Artemether+lumefantrine:
Percent of treatment failures (early treatment failure + late clinical failure + late parasitological failure) for artemether+lumefantrine. It is composite primary outcome.


Enrolled patients will be assessed for parasitological (using microscopy), clinical responses during the 28 days follow-up and treatment outcomes will be classified according to the latest WHO protocol.[At day 28 following initiation of artemether+lumefantrine treatment.]

Artesunate+amodiaquine:
Percent of treatment failures (early treatment failure + late clinical failure + late parasitological failure) for artesunate+amodiaquine. It is composite primary outcome.

Enrolled patients will be assessed for parasitological (using microscopy), clinical responses during the 28 days follow-up and treatment outcomes will be classified according to the latest WHO protocol.[At day 28 following initiation of treatment of artesunate+amodiaquine treatment.]

Secondary Outcome(s)

Artesunate+amodiaquine:
Percent of adverse event will be documented. abdominal pain, asthenia, cough, diarrhoea, dizziness, insomnia, loss of appetite, nausea, vomiting.

Patients or parents/guardians of enrolled patients 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 day 28 following initiation of artesunate+amodiaquine treatment.]

Prevalence of artemisinin resistance molecular markers (K13). Parasite DNA will be extracted from the dried blood spots and will be analyzed by PCR and sequencing for the presence of molecular markers of resistance to artemisinin specifically to K13-propeller. [At Day 0 (prior of initiation of treatment)]

Dihydroartemisinin+piperaquine:
Percent of adverse event will be documented. The known adverse events of dihydroartemisinin/piperaquine are abdominal discomfort, nausea, headache and dizziness.

Patients or parents/guardians of enrolled patients 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 day 42 following initiation of dihydroartemisinin+piperaquine treatment.]

Artemether+lumefantrine:
Percent of adverse event will be documented. The known adverse events of artemether/lumefantrine are abdominal discomfort, nausea, headache and dizziness.

Patients or parents/guardians of enrolled patients 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 day 28 following initiation of artemether+lumefantrine treatment.]

Secondary ID(s)

Nil

Source(s) of Monetary Support

World Health Organization

Secondary Sponsor(s)

National Malaria Control Centre

Ethics review

Status: Approved
Approval date:
Contact:

WHO Ethical Research Committee