Overview

This trial is active, not recruiting.

Condition malaria
Treatments artemether lumefantrine, dihydroartemisinin piperaquine
Phase phase 3
Sponsor Sabah Ahmed Omar
Collaborator World Bank
Start date April 2013
End date June 2014
Trial size 2100 participants
Trial identifier NCT01899820, KEMRI_CT_2013/0017, SSC 2276

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

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking single blind (caregiver)
Primary purpose treatment
Arm
(Active Comparator)
Tablets, 1-4 tablets (weight calculated dose), BD, at hr 0, 8, 24, 36, 48 and 60.
artemether lumefantrine Coartem
Artemether 20mg Lumefantrine 120mg
(Experimental)
Tablets, 2 paediatric tablets/1 adult tablet, OD, every 24 hours for 48 hours
dihydroartemisinin piperaquine Duocortexin
Dihydroartemisinin 20mg Piperaquine 160mg

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.
time frame: Day 28 and day 42

Secondary Outcomes

Measure
Crude (PCR uncorrected) ACPR ratio at day 28 (PCR uncorrected ACPR)
time frame: Day 28
Cure ratios at day 28, 42, (PCR corrected and PCR uncorrected). Change in this outcome measure will be assessed.
time frame: Day 28 and day 42
Fever Clearance Time (FCT)
time frame: 0 to 48 hours
Asexual parasite clearance time (PCT)
time frame: Day 0 to day 28, upto day 42
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.
time frame: Day 7, 14, 28 and 42
Changes of haemoglobin (Hb) concentration from day 0 to days 28, and 42
time frame: Day 0, day 28 and day 42
Number of participants with adverse events
time frame: Up to day 42
Comparison between adverse events related to artemether lumefantrine and dihydroartemisinin piperaquine
time frame: Up to day 42
Temperature
time frame: Up to day 42
Oxygen saturation
time frame: Up to day 42
Heart rate
time frame: Up to day 42
Respiratory rate
time frame: Up to day 42

Eligibility Criteria

Male or female participants from 6 months up to 10 years old.

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).

Additional Information

Official title Evaluation of the Efficacy of Artemisinin Combination Therapy in Kenya
Principal investigator Sabah A Omar, PhD
Trial information was received from ClinicalTrials.gov and was last updated in October 2013.
Information provided to ClinicalTrials.gov by KEMRI-Wellcome Trust Collaborative Research Program.