Treatment Efficacy and Malaria TRANSmission After Artemisinin Combination Therapy 2 (TRANSACT2)
Information source: London School of Hygiene and Tropical Medicine
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Malaria
Intervention: Mefloquine - Artesunate (Drug); Artemether-lumefantrine combination (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: London School of Hygiene and Tropical Medicine Official(s) and/or principal investigator(s): Patrick Sawa, MB.Ch.B, MSc., Principal Investigator, Affiliation: KCMC/ICIPE Jaffu Chilongola, PhD, Principal Investigator, Affiliation: KCMC Colin Sutherland, PhD, Study Director, Affiliation: LSHTM Henk Schallig, PhD, Study Chair, Affiliation: KIT, Amsterdam
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
Clinical Details
Official title: Treatment Efficacy and Malaria TRANSmission After Artemisinin Combination Therapy 2 (TRANSACT2)
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Caregiver, Investigator), Primary Purpose: Treatment
Primary outcome: the number of participants with clinical and parasitological treatment failure after treatment artemether-lumefantrine (AL) and mefloquine-artesunate MQ-AS
Secondary outcome: the number of individuals with gametocytes after treatment with AL or MQ-AS
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
Minimum age: 6 Months.
Maximum age: 10 Years.
Gender(s): Both.
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.
Locations and Contacts
St. Jude's Clinic, ICIPE Thomas Odhiambo Campus, Mbita, Nyanza 40305, Kenya
Additional Information
Related publications: 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. 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.
Starting date: April 2013
Last updated: November 27, 2013
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