Evaluation of the Efficacy of Artemisinin Combination Therapy in Kenya

NCT ID: NCT01899820

Last Updated: 2013-10-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 2100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-30
• Study Completion Date: 2015-07-31

Brief Summary

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

Conditions

Malaria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Artemether lumefantrine

Tablets, 1-4 tablets (weight calculated dose), BD, at hr 0, 8, 24, 36, 48 and 60.

Group Type: ACTIVE_COMPARATOR

Artemether lumefantrine

Intervention Type: DRUG

Artemether 20mg Lumefantrine 120mg

Dihydroartemisinin piperaquine

Tablets, 2 paediatric tablets/1 adult tablet, OD, every 24 hours for 48 hours

Group Type: EXPERIMENTAL

Dihydroartemisinin piperaquine

Intervention Type: DRUG

Dihydroartemisinin 20mg Piperaquine 160mg

Interventions

Artemether lumefantrine

Artemether 20mg Lumefantrine 120mg

Intervention Type: DRUG

Dihydroartemisinin piperaquine

Dihydroartemisinin 20mg Piperaquine 160mg

Intervention Type: DRUG

Other Intervention Names

Coartem; Duocortexin

Eligibility Criteria

Inclusion Criteria

1. Age between 6 months - 5 years (in high endemic areas); 6 months to 10 years (in low endemic areas) inclusive.

2. Presence of axillary temperature > 37.5oC or rectal / tympanic temp > 38.0oC, or history of fever in the last 24 hours.

3. 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)

4. Ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule; and

5. Signed informed consent form by the parents or legal guardian.

Exclusion Criteria

1. 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;

2. Mixed or mono-infection with another Plasmodium species detected by microscopy;

3. 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);

4. History of hypersensitivity reactions or contraindications to any of the medicine(s) being tested or used as alternative treatment(s).

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 10 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

World Bank

OTHER

Sponsor Role: collaborator

Kenya Medical Research Institute

OTHER

Sponsor Role: collaborator

Sabah Ahmed Omar

OTHER

Sponsor Role: lead

Responsible Party

Sabah Ahmed Omar

Centre Director of KEMRI CGMR-C and Study Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Sabah A Omar, PhD

Role: PRINCIPAL_INVESTIGATOR

KEMRI CGMR-C

Locations

Busia district hospitals

Busia, Busia County, Kenya

Kisii district hospitals

Kisii, Kisii County, Kenya

Kitale district hospitals

Kitale, Kitale, Kenya

Msambweni sub-district hospital

Msambweni, Kwale County, Kenya

Machakos district hospital

Machakos, Machakos County, Kenya

Malindi district hospitals

Malindi, Malindi, Kenya

Nyando district hospital

Nyando, Nyando, Kenya

Countries

Kenya

Other Identifiers

SSC 2276

Identifier Type: OTHER

Identifier Source: secondary_id

KEMRI_CT_2013/0017

Identifier Type: -

Identifier Source: org_study_id