Have Malaria Infections in Kenya Become Less Responsive to Artemisinin Treatment?

NCT ID: NCT01190371

Last Updated: 2018-02-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 175 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-30
• Study Completion Date: 2018-12-31

Brief Summary

The purpose of this study is to determine whether P. falciparum infections in Kilifi District have developed tolerance to the artemisinin class of drugs.

Detailed Description

Artemisinin-based combination therapies (ACT) are the treatment of choice for episodes of uncomplicated P. falciparum malaria in all endemic countries. Rapid clearance of pathogenic blood stage malaria parasites by artemisinins is associated with swift recovery from mild malaria and reduced mortality from severe forms of the disease. In Kenya, and most malaria endemic sub-saharan Africa, artemether-lumefantrine has been introduced as first-line treatment in the public health care sector in 2006. Alarmingly, despite the short time since the introduction of ACTs artemisinin-resistant P. falciparum malaria has already emerged in South-East Asia, an area that has historically been the cradle of global spreads of drug-resistant malaria parasites.

In a previous study in Kilifi we have observed a significant drop in early response rates to treatment with two ACTs from 2005 to 2008. Conventional markers of potential changes in anti-parasitic host immunity, drug exposure, or baseline parasite biomass could not account for the observed time-dependent change in response rates.

This protocol aims to establish with reasonable confidence whether P. falciparum infections in Kilifi District have developed tolerance to the artemisinin class of drugs. We propose to study treatment response rates to an established 7-day regimen of artesunate alone in the treatment of uncomplicated P. falciparum malaria in children aged 6 months to 10 years, at the KEMRI study site in Pingilikani, Kilifi District, Kenya. The study will also assess (i) pharmacokinetic parameters of artesunate; (ii) ex vivo and in vitro chemosensitivity of parasite isolates to DHA; (iii) genetic determinants of altered in vivo and in vitro responses to DHA; and (iv) ex vivo expression profiles in normally vs. slowly responding P. falciparum infections before and during treatment.

Conditions

Malaria

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Artesunate

Confirmation of artemisinin tolerance

Group Type: OTHER

Artesunate

Intervention Type: DRUG

Oral, once daily, 7-day regimen of artesunate 2mg/kg/day

Interventions

Artesunate

Oral, once daily, 7-day regimen of artesunate 2mg/kg/day

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• aged between 6 months to 10 years, inclusive
• mono-infection with P. falciparum detected by microscopy;
• parasitaemia of 10,000-300,000/µl asexual forms;
• presence of axillary temperature ≥ 37.5 °C or history of fever during the past 24 h;
• ability to swallow oral medication;
• ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule; and
• informed consent from a parent or 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 severe acute malnutrition defined as weight for height <70% of the median NCHS/WHO (Appendix 2);
• presence of febrile conditions due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhoea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases, HIV/AIDS);
• regular medication, which may interfere with antimalarial pharmacokinetics or pharmacodynamic assessments (e.g., antibiotics with known antimalarial activity); and
• 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

University of Oxford

OTHER

Sponsor Role: collaborator

Heidelberg University

OTHER

Sponsor Role: collaborator

KEMRI-Wellcome Trust Collaborative Research Program

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Roma Chilengi

Role: PRINCIPAL_INVESTIGATOR

KEMRI Centre for Geographic Medicine Research (Coast), University of Oxford, England

Steffen Borrmann

Role: PRINCIPAL_INVESTIGATOR

KEMRI Centre for Geographic Medicine Research (Coast), Heidelberg University of Medicine, Germany

Locations

Kadzinuni Dispensary

Kadzinuni, Kilifi County, Kenya

Junju Dispensary

Kilifi, , Kenya

Pingilikani Dispensary

Kilifi, , Kenya

Countries

Kenya

Other Identifiers

SSC 1821

Identifier Type: OTHER

Identifier Source: secondary_id

KEMRI_CT_2010/0013

Identifier Type: -

Identifier Source: org_study_id