Clinical trial NCT01939886: Treatment Efficacy and Malaria TRANSmission After Artemisinin Combination Therapy 2 (TRANSACT2)
Official title: Treatment Efficacy and Malaria TRANSmission After Artemisinin Combination Therapy 2 (TRANSACT2)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Malaria
Keywords: Malaria treatment efficacy
Malaria transmission
Lead sponsor: London School of Hygiene and Tropical Medicine
Sponsor class: OTHER
Collaborators: name: Kilimanjaro Christian Medical Centre, Tanzania
name: Radboud University Medical Center
name: European Union
First posted: 2013-09-11
Enrollment: 219
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 combination therapy (ACT) with artemether lumefantrine (AL) is currently the first line treatment policy in Kenya. 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. Clinical trials in Asia showed that mefloquine-artesunate (MQ-AS) may be more efficacious than AL and may have a more pronounced beneficial effect on post-treatment malaria transmission. MQ-AS is registered and used in Kenya but there have been no reported direct comparisons of AL and MQ-AS with clinical and transmission endpoints (i.e. adequately clearing parasites and preventing transmission to mosquitoes).

Screening for molecular markers that are related to parasite susceptibility to ACT drugs and to post-ACT treatment malaria transmission can assist strategies to prevent the development and spread of ACT resistance.

In the current study, we compare AL and MQ-AS for the treatment of uncomplicated malaria. Our endpoints are i) clinical efficacy, ii) post-treatment gametocytaemia by molecular techniques.

In the current study, the investigators compare AL and MQ-AS for the treatment of uncomplicated malaria. The investigators endpoints are

clinical efficacy post-treatment gametocytaemia by molecular techniques

Detailed description: Accurate diagnosis followed by prompt and efficacious treatment is the backbone of any malaria control programme. However, malaria treatment has been facing huge challenges in recent years. A number of affordable antimalarial drugs have been used to cure malaria since the 1940s: these include chloroquine (CQ), sulphadoxine-pyrimethamine (SP; Fansidar®), mefloquine (MQ), amodiaquine (AQ) and quinine. The emergence and spread of resistance to these commonly-used drugs has been largely responsible for the worsening of the malaria situation observed in the past decades.

Across the African continent, guidelines have recently been changed. The World Health Organization (WHO) recommends for falciparum malaria the use of combination therapies, preferably those containing artemisinin derivatives (ACT, artemisinin-based combination therapy). Artemisinin derivatives, e.g. artesunate, artemether and dihydroartemisinin, being extremely potent antimalarial agents are the ideal partners in combinations with other antimalarials. ACTs have three demonstrable advantages over conventional therapy, they i) are efficacious in clearing asexual parasites, ii) substantially reduce post-treatment gametocyte carriage and iii) "protect" the partner drug from selecting resistant parasites.

In Kenya, both CQ and SP have lost clinical efficacy. CQ was replaced by SP in 1998 and in the year 2006, SP was effectively replaced by Artemether-Lumefantrine (AL: Coartem®). The policy change to the artemisinin-based drug AL is in line with the WHO recommendations to shift to ACT as first line antimalarial treatment.The most efficacious ACT, however, needs local comparisons in terms of treatment efficacy and transmission-reducing activity.

Eligibility 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.

Primary outcomes:
measure: the number of participants with clinical and parasitological treatment failure after treatment artemether-lumefantrine (AL) and mefloquine-artesunate MQ-AS
timeFrame: 42 day follow-up
Secondary outcomes:
measure: the number of individuals with gametocytes after treatment with AL or MQ-AS
timeFrame: 42 days follow-up
Other outcomes:
Locations:
city: Mbita
country: Kenya
facility: St. Jude's Clinic, ICIPE Thomas Odhiambo Campus
state: Nyanza
Study officials:
affiliation: KCMC/ICIPE
name: Patrick Sawa, MB.Ch.B, MSc.
role: PRINCIPAL_INVESTIGATOR
affiliation: KCMC
name: Jaffu Chilongola, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: London School of Hygiene and Tropical Medicine
name: Colin Sutherland, PhD
role: STUDY_DIRECTOR
affiliation: KIT, Amsterdam
name: Henk Schallig, PhD
role: STUDY_CHAIR
References:
citation: Beshir KB, Sutherland CJ, Sawa P, Drakeley CJ, Okell L, Mweresa CK, Omar SA, Shekalaghe SA, Kaur H, Ndaro A, Chilongola J, Schallig HD, Sauerwein RW, Hallett RL, Bousema T. Residual Plasmodium falciparum parasitemia in Kenyan children after artemisinin-combination therapy is associated with increased transmission to mosquitoes and parasite recurrence. J Infect Dis. 2013 Dec 15;208(12):2017-24. doi: 10.1093/infdis/jit431. Epub 2013 Aug 14.
citation: Sawa P, Shekalaghe SA, Drakeley CJ, Sutherland CJ, Mweresa CK, Baidjoe AY, Manjurano A, Kavishe RA, Beshir KB, Yussuf RU, Omar SA, Hermsen CC, Okell L, Schallig HD, Sauerwein RW, Hallett RL, Bousema T. Malaria transmission after artemether-lumefantrine and dihydroartemisinin-piperaquine: a randomized trial. J Infect Dis. 2013 Jun 1;207(11):1637-45. doi: 10.1093/infdis/jit077. Epub 2013 Mar 6.