Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01899820
Recruitment Status : Unknown
Verified October 2013 by Sabah Ahmed Omar, KEMRI-Wellcome Trust Collaborative Research Program.
Recruitment status was:  Active, not recruiting
First Posted : July 15, 2013
Last Update Posted : October 8, 2013
Sponsor:
Collaborators:
World Bank
Kenya Medical Research Institute
Information provided by (Responsible Party):
Sabah Ahmed Omar, KEMRI-Wellcome Trust Collaborative Research Program

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

Condition or disease Intervention/treatment Phase
Malaria Drug: Artemether lumefantrine Drug: Dihydroartemisinin piperaquine Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Care Provider)
Primary Purpose: Treatment
Official Title: Evaluation of the Efficacy of Artemisinin Combination Therapy in Kenya
Study Start Date : April 2013
Estimated Primary Completion Date : June 2014
Estimated Study Completion Date : July 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
Active Comparator: Artemether lumefantrine
Tablets, 1-4 tablets (weight calculated dose), BD, at hr 0, 8, 24, 36, 48 and 60.
Drug: Artemether lumefantrine
Artemether 20mg Lumefantrine 120mg
Other Name: Coartem

Experimental: Dihydroartemisinin piperaquine
Tablets, 2 paediatric tablets/1 adult tablet, OD, every 24 hours for 48 hours
Drug: Dihydroartemisinin piperaquine
Dihydroartemisinin 20mg Piperaquine 160mg
Other Name: Duocortexin




Primary Outcome Measures :
  1. 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 ]

    ACPR is defined as the absence of parasitaemia on day 42 irrespective of the temperature without previously meeting any of the criteria of early treatment failure or late clinical or parasitological failure.

    Patients with late asexual parasite reappearance will be considered ACPR if the CR analyses shows a new infection rather than a recrudescence (through PCR genotyping).

    The total treatment failure is defined according to the WHO criteria as the sum of early and late treatment failures.



Secondary Outcome Measures :
  1. Crude (PCR uncorrected) ACPR ratio at day 28 (PCR uncorrected ACPR) [ Time Frame: Day 28 ]
  2. 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 ]
  3. Fever Clearance Time (FCT) [ Time Frame: 0 to 48 hours ]
    This will be defined as the time (hrs) from the start of a patient's treatment to the first consecutive axillary temp measurements below 37.5 for at least 48 hrs

  4. Asexual parasite clearance time (PCT) [ Time Frame: Day 0 to day 28, upto day 42 ]
    PCT(proportion of patients remaining parasitaemic) defined as the time (in hours) from the start of a patient's treatment to 2 consecutive negative blood slides (collected at different days)

  5. 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 ]
  6. Changes of haemoglobin (Hb) concentration from day 0 to days 28, and 42 [ Time Frame: Day 0, day 28 and day 42 ]
  7. Number of participants with adverse events [ Time Frame: Up to day 42 ]
  8. Comparison between adverse events related to artemether lumefantrine and dihydroartemisinin piperaquine [ Time Frame: Up to day 42 ]
  9. Temperature [ Time Frame: Up to day 42 ]
  10. Oxygen saturation [ Time Frame: Up to day 42 ]
  11. Heart rate [ Time Frame: Up to day 42 ]
  12. Respiratory rate [ Time Frame: Up to day 42 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   6 Months to 10 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01899820


Locations
Layout table for location information
Kenya
Msambweni sub-district hospital
Msambweni, Kwale, Kenya
Busia district hospitals
Busia, Kenya
Kisii district hospitals
Kisii, Kenya
Kitale district hospitals
Kitale, Kenya
Machakos district hospital
Machakos, Kenya
Malindi district hospitals
Malindi, Kenya
Nyando district hospital
Nyando, Kenya
Sponsors and Collaborators
Sabah Ahmed Omar
World Bank
Kenya Medical Research Institute
Investigators
Layout table for investigator information
Principal Investigator: Sabah A Omar, PhD KEMRI CGMR-C
Layout table for additonal information
Responsible Party: Sabah Ahmed Omar, Centre Director of KEMRI CGMR-C and Study Principal Investigator, KEMRI-Wellcome Trust Collaborative Research Program
ClinicalTrials.gov Identifier: NCT01899820    
Other Study ID Numbers: KEMRI_CT_2013/0017
SSC 2276 ( Other Identifier: KEMRI Scientific Steering Committee )
First Posted: July 15, 2013    Key Record Dates
Last Update Posted: October 8, 2013
Last Verified: October 2013
Additional relevant MeSH terms:
Layout table for MeSH terms
Malaria
Protozoan Infections
Parasitic Diseases
Infections
Vector Borne Diseases
Lumefantrine
Artemether
Piperaquine
Artemether, Lumefantrine Drug Combination
Artenimol
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents