Improving Anti-malarial Treatment Options in Guinea-Bissau - Part A
Efficacy and Safety of Artemether + Lumefantrine and Dihydroartemisinin + Piperaquine for the Treatment of Uncomplicated Malaria in Guinea-Bissau.
1 other identifier
interventional
346
1 country
1
Brief Summary
Plasmodium falciparum causes malaria and approximately 665 000 deaths each year. chloroquine and sulphadoxine-pyrimethamine resistant P. falciparum are widespread. An artemisinin derivative combined with lumefantrine, amodiaquine or piperaquine is therefore recommended for the treatment of malaria in Africa. However, artemisinin resistance appears to be developing and resistance/tolerance to amodiaquine and lumefantrine exists. We are presently conducting a study in Guinea-Bissau. Preliminary data indicates that the effectiveness and availability of artemether-lumefantrine (AL), the 1st line drug, is poor. Consequently there is a need for another treatment option. Dihydroartemisinin-piperaquine (DP) has been shown to be efficacious and well tolerated in several African countries and is therefore such an option. A clinical trial comparing the safety and efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine is therefore needed. Parents to children seeking Bandim Health Centre (CSB) with symptoms compatible with malaria will be informed of the study. If accepting and the child fulfil the inclusion criteria, the child will be randomised to treatment with either AL or DP. The treatment will be given supervised at the health centre in the morning and the evening on day 0, day 1, and day 2. At each visit and in the morning on day 3, the child will be examined, the mother asked for any symptoms and signs of side-effects, the temperature measured. Furthermore, a blood sample will be taken for examination of malaria parasites. On day 0 samples for measurement of antimalarial drugs and for genotyping of the parasites will be taken on filterpaper. In a subgroup of 50 children a blood sample for in vitro culturing and for analysis of the number of leucocytes will also be taken. After having finished the treatment the children will be followed on day 7 and then once a week until day 42. At each visit the condition of the child will be examined and a bloodsample taken for examination of parasites in the blood. Furthermore, a filterpaper bloodsample will be collected for measurement of the drug concentration of if the child has recrudescence for genotyping of the parasites. On day 0, 3 and 42 the haemoglobin level will be examined. The result of the two treatments will be evaluated by comparing the number of children with recurrent parasitaemia, both corrected and uncorrected (recrudescence vs. reinfections). This will be presented as adequate clinical and parasitological response rates PCR-corrected and PCR-uncorrected. Furthermore, the chance in haemoglobin level from day 0 till day 3 and till day 42 will be compared. The concentration of the antimalarial drug in the blood samples taken at the visit before the re-parasitaemia will be capered to the concentrations in children without re-parasitaemia. Assuming a 20% loss to follow up a total of 346 children should be included. For the children included, health care and medications at Bandim Health Centre will be free during the study period but no other gifts or payments will be made. Results will be presented to the staff at the Bandim health centre and the ministry of Health and will be published in an international peer reviewed journal.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Nov 2012
Longer than P75 for phase_4
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 9, 2012
CompletedFirst Posted
Study publicly available on registry
October 11, 2012
CompletedStudy Start
First participant enrolled
November 1, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2016
CompletedMay 26, 2021
August 1, 2015
2.9 years
October 9, 2012
May 25, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Adequate clinical and parasitological response rate
The data will be analysed using survival estimates of per protocol treatment failure rates but also intention to treat treatment failure rates.
42 days
Secondary Outcomes (1)
the safety of AL and DP
42 days
Other Outcomes (3)
To determine the capacity of each drug combination to protect against re-infection and to differentiate recrudescence from re-infections using PCR based methods
42 days
Genetic polymorphisms in P. falciparum causing reparasitaemia (by PCR) and in 50 children perform a characterisation of P. falciparum geno- and phenotypes.
42 days
haemoglobin values
days 0, 3 and 42
Study Arms (2)
Artemether-lumefantrine
ACTIVE COMPARATOR6-dose regime will be used:
Dihydroartemisinin-piperaquine
ACTIVE COMPARATORA 3 dose regime will be used
Interventions
Eligibility Criteria
You may qualify if:
- A) Age ≥6 months, and \<13 years. B) Mono-infection with P. falciparum detected by microscopy. C) Parasitemia of 1.000-200.000/µl asexual forms. D) Axillary temperature ≥37.5 ˚C or a history of fever within 24 hours. E) Ability to swallow oral medication.
- F) Ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule. G) Informed consent from a parent or guardian
You may not qualify if:
- A) Signs or symptoms of severe malaria, incl. hyperparasitaemia (\>200.000/ µl asexual forms) B) Presence of general danger signs in children under 5 C) Presence of severe malnutrition. D) Any evidence of chronic disease or acute infection other than malaria. E) Regular medication which may interfere with antimalarial pharmacokinetics. F) History of hypersensitivity reactions or contraindications to AL, DP or quinine.
- G) Domicile outside the study area.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Bandim Health Projectlead
- Karolinska Institutetcollaborator
Study Sites (1)
Bandim Health Project
Bissau, Guinea-Bissau
Related Publications (1)
Jovel IT, Kofoed PE, Rombo L, Rodrigues A, Ursing J. Temporal and seasonal changes of genetic polymorphisms associated with altered drug susceptibility to chloroquine, lumefantrine, and quinine in Guinea-Bissau between 2003 and 2012. Antimicrob Agents Chemother. 2015 Feb;59(2):872-9. doi: 10.1128/AAC.03554-14. Epub 2014 Nov 24.
PMID: 25421474DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 9, 2012
First Posted
October 11, 2012
Study Start
November 1, 2012
Primary Completion
October 1, 2015
Study Completion
July 1, 2016
Last Updated
May 26, 2021
Record last verified: 2015-08