Treatment Efficacy and Malaria TRANSmission After Artemisinin Combination Therapy (TRANSACT) - Full Text View

Sponsors and Collaborators:	Radboud University Kilimanjaro Christian Medical Centre, APRIORI programme European Union, FP7-HEALTH-2007-Grant agreement no.: 201889
Information provided by:	Radboud University
ClinicalTrials.gov Identifier:	NCT00868465

Purpose

Artemisinin combination therapy (ACT) with artemether lumefantrine (AL) is currently the first line treatment policy in Tanzania. AL is an efficacious drug that also has the capacity to reduce malaria transmission to mosquitoes. Nevertheless, there is concern about the development of parasite resistance against AL and there have been very few clinical trials that compared different ACT regimens. A recent clinical trial shows that the combination of dihydroartemisinin-piperaquine (DP) may be more efficacious than AL and may have a more pronounced beneficial effect on post-treatment malaria transmission. Screening for molecular markers that are related to parasite susceptibility to ACT drugs and to post-ACT treatment malaria transmission can assist in preventing the development and spread of ACT resistance. In the current study, the investigators compared AL and DP for the treatment of uncomplicated malaria. The investigators endpoints are

clinical efficacy
post-treatment gametocytaemia by molecular techniques
post-treatment malaria transmission.

Condition	Intervention
Uncomplicated Malaria	Drug: Artemether-Lumefantrine Drug: Dihydroartemisinin-piperaquine

MedlinePlus related topics: Malaria

Drug Information available for: Artemisinin Dihydroquinghaosu Artemether Benflumetol Piperaquine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Outcomes Assessor), Active Control, Parallel Assignment, Efficacy Study

Further study details as provided by Radboud University:

Primary Outcome Measures:

To determine the clinical efficacy of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) in the treatment of uncomplicated falciparum malaria in children living in north-western Tanzania and in western Kenya. [ Time Frame: during 42 day follow-up ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To determine (sub-microscopic) gametocyte carriage after treatment with AL and DP [ Time Frame: during 42 day follow-up ] [ Designated as safety issue: No ]
To determine malaria transmission to mosquitoes after treatment with AL or DP [ Time Frame: day 7 after initiation treatment ] [ Designated as safety issue: No ]
To determine molecular markers that are predictive of reduced susceptibility of parasite strains for AL and DP [ Time Frame: day 7 after initiation treatment ] [ Designated as safety issue: No ]
To determine molecular markers that are related to gametocytaemia or malaria transmission after treatment with AL and DP [ Time Frame: during 42 day follow-up ] [ Designated as safety issue: No ]
To determine the relation between treatment success and the presence of anti-malaria antibodies [ Time Frame: during 42 day follow-up ] [ Designated as safety issue: No ]
To explore the role of cellular oxidative stress in treatment with AL and DP [ Time Frame: during 42 day follow-up ] [ Designated as safety issue: No ]
To determine the relation between transmission to mosquitoes and the presence of anti-malaria antibodies [ Time Frame: day 7 after initiation treatment ] [ Designated as safety issue: No ]

Estimated Enrollment:	600
Study Start Date:	April 2009
Estimated Study Completion Date:	September 2009
Estimated Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Artemether-lumefantrine; currently the first line treatment in Tanzania	Drug: Artemether-Lumefantrine Treatment with artemether-lumefantrine (AL; Coartem; Novartis Pharma), administered as half a tablet (20 mg of artemether and 120 mg of lumefantrine) per 5 kg of body weight in a 6-dose regimen (at enrolment and 8, 20, 32, 44, and 56 h [+/-90 min] after the initiation of treatment). AL is currently the first line treatment in Tanzania
2: Experimental Dihydroartemisinin-piperaquine, alternative ACT	Drug: Dihydroartemisinin-piperaquine Dihydroartemisinin-piperaquine (DP; Artekin; Duocotexin, Holley Pharm, 40 mg dihydroartemisinin/320 mg piperaquine tablets), with a dihydroartemisinin dose of 2.5 mg per kilogram and a piperaquine phosphate dose of 20 mg per kilogram daily for 3 days. DH is registered in Tanzania as Artekin and has been tested extensively in Asia and recently in clinical trials in Uganda and Rwanda

Arms

Assigned Interventions

1: Active Comparator

Artemether-lumefantrine; currently the first line treatment in Tanzania

Drug: Artemether-Lumefantrine

Treatment with artemether-lumefantrine (AL; Coartem; Novartis Pharma), administered as half a tablet (20 mg of artemether and 120 mg of lumefantrine) per 5 kg of body weight in a 6-dose regimen (at enrolment and 8, 20, 32, 44, and 56 h [+/-90 min] after the initiation of treatment). AL is currently the first line treatment in Tanzania

2: Experimental

Dihydroartemisinin-piperaquine, alternative ACT

Drug: Dihydroartemisinin-piperaquine

Dihydroartemisinin-piperaquine (DP; Artekin; Duocotexin, Holley Pharm, 40 mg dihydroartemisinin/320 mg piperaquine tablets), with a dihydroartemisinin dose of 2.5 mg per kilogram and a piperaquine phosphate dose of 20 mg per kilogram daily for 3 days. DH is registered in Tanzania as Artekin and has been tested extensively in Asia and recently in clinical trials in Uganda and Rwanda

Show Detailed Description

Eligibility

Ages Eligible for Study:	6 Months to 10 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age 6 months - 10 years
Residents of research area (5 km around the clinic)
Willingness to come for complete scheduled follow-up.
Uncomplicated malaria with P. falciparum mono-infection
Parasitaemia of 1000-200,000 parasites/ul
Temperature > 37.5°C and < 39.5°C, or history of fever in previous 24 hours.
No history of adverse reactions to AL
Understanding of the procedures of the study by parent or guardian and willing to participate by signing informed consent forms.

Exclusion Criteria:

General signs of severe malaria
Haemoglobin concentration < 5g/dl
Presence of disease other than malaria causing febrile conditions
Mixed infection with P. malariae or other non-falciparum malaria species
Unwilling to participate and sign informed consent forms.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00868465

Contacts

Contact: Teun Bousema, PhD	+255 782390707	jt_bousema@yahoo.co.uk
Contact: Seif Shekalaghe, MD	+255 755470472	sshekalaghe@yahoo.com

Locations

Kenya, Suba District
International Centre for Insect Physiology and Ecology - St. Judes Clinic	Recruiting
Mbita, Suba District, Kenya
Contact: Patrick Sawa, MD +254 59 22620 psawa@mbita.mimcom.net
Contact: Hortance Manda, PhD +254 59 22217 hmanda@mbita.mimcom.net
Principal Investigator: Patrick Sawa, MD
Tanzania, Kilimanjaro Region
Kilimanjaro Christian Medical Centre, Magugu Field Site	Not yet recruiting
Moshi, Kilimanjaro Region, Tanzania
Contact: Seif Shekalaghe, MD +255 755470472 sshekalaghe@yahoo.com
Contact: Frank Mosha, PhD +255 784317316 fwmosha@hotmail.com
Principal Investigator: Seif Shekalaghe, MD

Sponsors and Collaborators

Radboud University

Kilimanjaro Christian Medical Centre, APRIORI programme

European Union, FP7-HEALTH-2007-Grant agreement no.: 201889

More Information

Publications:

Bousema JT, Schneider P, Gouagna LC, Drakeley CJ, Tostmann A, Houben R, Githure JI, Ord R, Sutherland CJ, Omar SA, Sauerwein RW. Moderate effect of artemisinin-based combination therapy on transmission of Plasmodium falciparum. J Infect Dis. 2006 Apr 15;193(8):1151-9. Epub 2006 Mar 15.

Hallett RL, Sutherland CJ, Alexander N, Ord R, Jawara M, Drakeley CJ, Pinder M, Walraven G, Targett GA, Alloueche A. Combination therapy counteracts the enhanced transmission of drug-resistant malaria parasites to mosquitoes. Antimicrob Agents Chemother. 2004 Oct;48(10):3940-3.

Responsible Party:	Kilimanjaro Christian Medical Centre ( Teun Bousema )
Study ID Numbers:	TRANSACT09
Study First Received:	March 24, 2009
Last Updated:	April 6, 2009
ClinicalTrials.gov Identifier:	NCT00868465 History of Changes
Health Authority:	Tanzania: National Institute for Medical Research; Kenya: KEMRI Ethical Review Committee

Study placed in the following topic categories:

Benflumetol
Protozoan Infections
Artemether-lumefantrine combination
Clotrimazole
Miconazole
Artemisinine
Tioconazole
Malaria

Anthelmintics
Artemether
Piperaquine
Antimalarials
Artemisinins
Antifungal Agents
Parasitic Diseases
Dihydroquinghaosu

Additional relevant MeSH terms:

Benflumetol
Protozoan Infections
Anti-Infective Agents
Antiprotozoal Agents
Antiplatyhelmintic Agents
Coccidiosis
Anthelmintics
Malaria
Schistosomicides
Pharmacologic Actions

Artemether
Piperaquine
Antimalarials
Antiparasitic Agents
Artemisinins
Antifungal Agents
Therapeutic Uses
Parasitic Diseases
Dihydroquinghaosu
Coccidiostats

ClinicalTrials.gov processed this record on May 07, 2009