Evaluation of the Efficacy of Artemisinin Combination Therapy in Kenya (EAPHLNP)

Sabah Ahmed Omar

Status and phase

Unknown

Phase 3

Conditions

Malaria

Treatments

Drug: Artemether lumefantrine

Drug: Dihydroartemisinin piperaquine

Study type

Interventional

Funder types

Other

Identifiers

NCT01899820

SSC 2276 (Other Identifier)

KEMRI_CT_2013/0017

Details and patient eligibility

About

Artemisinin-based combination therapies (ACTs) are recommended for use against uncomplicated malaria in areas of multi-drug resistant malaria. The Ministry of Health, Division of Malaria Control (DOMC) rolled out the use of artemether-lumefantrine as the first line treatment for uncomplicated malaria in 2006.The development of the ACTs and its derivatives are the most rapidly acting of all the current antimalarial drugs and recognition of their potential role as a component of combination therapy have led to several large trials aimed at assessing different combinations of existing drugs, and to the specific development of new combination drugs.

This proposal aims to (1) evaluate the efficacy of artemisinin-based anti-malaria combination drugs in different sites across Kenya (2) elucidate the markers of resistance to ACTs through molecular genetics and in this process further strengthen capacity in the proposed study sites as well as improve links between research and control ultimately to influence malaria treatment policy and practice.

Five groups in East Africa will conduct a multi-centre, randomised, two arm trial to assess the efficacy of dihydroartemisin-piperaquine with artemether-lumefantrine as the comparative drug. The network will determine antimalarial drug efficacy using standardised protocols and collate clinical responses and adverse events. Molecular markers to artemisinin resistance will be investigated by molecular sequencing and comparison of parasite profiles in drug failure cases. Recrudescence or re-infections will be differentiated by analysis of the MSP1, MSP2 and GLURP genes and assess transmission dynamics post treatment. Data from these studies will be captured into a database developed by the network. The latter offers several advantages including

Working towards the standardization of methodologies and common protocols as a way of comparing data across sites
Pulling together datasets and conduct a multi-centre analysis
Sharing and coordinating quality assurance mechanisms

Enrollment

2,100 estimated patients

Sex

All

Ages

6 months to 10 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age between 6 months - 5 years (in high endemic areas); 6 months to 10 years (in low endemic areas) inclusive.
Presence of axillary temperature > 37.5oC or rectal / tympanic temp > 38.0oC, or history of fever in the last 24 hours.
Monoinfection with Plasmodium falciparum with parasitaemia, asexual parasitemia between 2,000 - 200,000 p/µl (in areas of high transmission); 1,000-100,000p/ µl (in areas of low to moderate malaria transmission)
Ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule; and
Signed informed consent form by the parents or legal guardian.

Exclusion criteria

Presence of clinical danger signs: not able to drink or breast-feed, vomiting (>twice in 24 hours), recent history of convulsions (>1 in 24h), unconscious state, unable to sit or stand;
Mixed or mono-infection with another Plasmodium species detected by microscopy;
Presence of co-morbid infection (e.g. acute lower respiratory tract infection, severe diarrhoea with dehydration, Severe Anaemia) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases,Epilepsy, HIV/AIDS);
History of hypersensitivity reactions or contraindications to any of the medicine(s) being tested or used as alternative treatment(s).