Clinical trial NCT01899820: Evaluation of the Efficacy of Artemisinin Combination Therapy in Kenya
Official title: Evaluation of the Efficacy of Artemisinin Combination Therapy in Kenya
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Malaria
Lead sponsor: KEMRI-Wellcome Trust Collaborative Research Program
Sponsor class: OTHER
Collaborators: name: World Bank
name: Kenya Medical Research Institute
First posted: 2013-07-15
Enrollment: 2100
Sex: ALL
Minimum age (years): 6
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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).

Primary outcomes:
measure: The primary endpoint will be the PCR-corrected and parasitological response (PCR corrected ACPR) at days 28 and 42. Change in this outcome measure will be assessed.
timeFrame: Day 28 and day 42
Secondary outcomes:
measure: Crude (PCR uncorrected) ACPR ratio at day 28 (PCR uncorrected ACPR)
timeFrame: Day 28
measure: Cure ratios at day 28, 42, (PCR corrected and PCR uncorrected). Change in this outcome measure will be assessed.
timeFrame: Day 28 and day 42
measure: Fever Clearance Time (FCT)
timeFrame: 0 to 48 hours
measure: Asexual parasite clearance time (PCT)
timeFrame: Day 0 to day 28, upto day 42
measure: Gametocyte carrier rates and geometric mean densities (excluding negatives) will be compared on days 7, 14, 28 and 42. Change in this outcome measure will be assessed.
timeFrame: Day 7, 14, 28 and 42
measure: Changes of haemoglobin (Hb) concentration from day 0 to days 28, and 42
timeFrame: Day 0, day 28 and day 42
measure: Number of participants with adverse events
timeFrame: Up to day 42
measure: Comparison between adverse events related to artemether lumefantrine and dihydroartemisinin piperaquine
timeFrame: Up to day 42
measure: Temperature
timeFrame: Up to day 42
measure: Oxygen saturation
timeFrame: Up to day 42
measure: Heart rate
timeFrame: Up to day 42
measure: Respiratory rate
timeFrame: Up to day 42
Other outcomes:
Locations:
city: Msambweni
country: Kenya
facility: Msambweni sub-district hospital
state: Kwale
city: Busia
country: Kenya
facility: Busia district hospitals
city: Kisii
country: Kenya
facility: Kisii district hospitals
city: Kitale
country: Kenya
facility: Kitale district hospitals
city: Machakos
country: Kenya
facility: Machakos district hospital
city: Malindi
country: Kenya
facility: Malindi district hospitals
city: Nyando
country: Kenya
facility: Nyando district hospital
Study officials:
affiliation: KEMRI CGMR-C
name: Sabah A Omar, PhD
role: PRINCIPAL_INVESTIGATOR
References: