Clinical trial NCT00682578: A Comparative Study of Artekin With Standard Malarial Treatment Regimes in Afghanistan
Official title: Randomized Clinical Trial of the Efficacy and Safety of Dihydroartimisinine+Papiraquine (Artekin) Compared With First Line Drugs for Treatment of Vivax and Uncomplicated Falciparum Malaria in Afghanistan
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Uncomplicated Falciparum Malaria
Vivax Malaria
Keywords: falciparum malaria
vivax malaria
dihydroartemisinin-piperaquine
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: Wellcome Trust
name: Ministry of public Health Afghanistan
First posted: 2008-05-22
Enrollment: 1086
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Malaria is a major public health problem in many provinces of Afghanistan the failure rate of chloroquine (CQ) and amodiaquine (AQ) treated Plasmodium falciparum(Pf) malaria has risen to more than 60% overall and as high as 90% in Jalalabad. CQ remains fully effective against P vivax, and sulphadoxine-pyrimethamine (SP) remains effective against P falciparum (10-15% of cases fail to cure). The current malaria treatment protocol still continuing CQ for P.vivax and adopted Artmisinine based combination therapy (ACT) for treating (Pf) malaria, as most than 50% malaria has being diagnosed clinically, so due to this and other operational reasons the protocol needs to be simplified.

By comparing 56 day PCR corrected cure rate of DHA-PPQ with the standard treatment regimen as primary objective and comparing the safety, gametocytecidal effect and parasite clearance time as secondary objectives, our study titled: Randomized, Open Label, controlled, non-inferiority clinical trial for comparison of Efficacy \& safety, will provide scientific evidence to lead the simplification and improvement of the standard malaria treatment regimen in Afghanistan; to adopt a policy of treating both vivax and falciparum malaria with the same drug regimen.

With a significance level (α) = 0.05 and a power=80%, the calculated sample size is 274 per study arm. Therefore about1100 patients (274 per study-arm: 548 patients with falciaprum malaria and 548 patients with vivax malaria) will be recruited in Malaria reference Centers (MRCs) of three malaria endemic provinces (Nangarhar in the east, Thakhar in the north-east and Faryab in the north-west of country) after signing written inform consent form, according the inclusion and exclusion criteria and will be treated as out patients by giving the randomized drug dose under observation of study team and followed-up daily for 3 days (as treatment course of either arm is once daily dose for three days) and after than weekly up to day 56. and the study is planed to conducted in 3 provinces of Afghanistan for approximately 2 years.

Patients will be assessed clinically as well necessary laboratory tests will be performed and all the bio-medical findings will be recorded in special patient case record form, the electronic form of which will be broth to Trop. Med of Mahidol University for final analysis. The patients will be receiving the reasonable transportation cost for follow-up visits as well as one bed-net at the end of enrollment.


Eligibility criteria: Inclusion Criteria:

* Uncomplicated falciparum or vivax malaria or mixed species infection, as confirmed in a peripheral blood slide.
* No signs of severe malaria
* Age over three months.
* Non-pregnant, (test for β-HCG in women of child-bearing age).
* Weight ≥5 kg
* Willingness to participate and written informed consent provided by the patient or in case of children by attending guardians/parents.
* Not enrolled in any other investigational drug study in the previous month

Exclusion Criteria:

* Clinical or laboratory features suggesting severe malaria.
* Known cardiac, renal, hepatic or other severe disease, or requirement for hospital treatment
* Recurrent vomiting.
* Not eligible for follow-up.
* Lactating mother
* Hyperparasitemia of P. falciparum \> 100,000/µL
* Treatment with Artesunate or Chloroquine in the past one month, Fansidar in the past one and the half months and Artekin in past 3 months.

Primary outcomes:
measure: PCR corrected adequate clinical and parasitological response (PCR corrected 'adequate clinical and parasitological response' or ACPR)
timeFrame: Day 56
Secondary outcomes:
measure: Crude or PCR uncorrected ACPR
timeFrame: Day 56
measure: Early treatment failure (failure to clear parasitaemia)
timeFrame: 7 days
measure: fever clearance times
timeFrame: Days
measure: parasite clearance times with no recrudescence over the observation period
timeFrame: days
measure: gametocyte clearance times
timeFrame: weeks
measure: Haemoglobin levels on day 14 compared to admission
timeFrame: day 14
measure: safety and tolerability (rate and severity of adverse events)
timeFrame: day 56
Other outcomes:
Locations:
city: Faryab
country: Afghanistan
facility: Provincial Malaria Control Centers (MRC)
city: Jalalabad
country: Afghanistan
facility: Provincial Malaria Control Centers (MRC)
city: Maimana
country: Afghanistan
facility: Provincial Malaria Control Centers (MRC)
city: Takhar
country: Afghanistan
facility: Provincial Malaria Control Centers (MRC)
Study officials:
affiliation: Provincial Malaria Control Centers (MRC)
name: Ghulam R Awab, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Awab GR, Imwong M, Pukrittayakamee S, Alim F, Hanpithakpong W, Tarning J, Dondorp AM, Day NP, White NJ, Woodrow CJ. Clinical trials of artesunate plus sulfadoxine-pyrimethamine for Plasmodium falciparum malaria in Afghanistan: maintained efficacy a decade after introduction. Malar J. 2016 Feb 25;15:121. doi: 10.1186/s12936-016-1167-z.
citation: Awab GR, Pukrittayakamee S, Imwong M, Dondorp AM, Woodrow CJ, Lee SJ, Day NP, Singhasivanon P, White NJ, Kaker F. Dihydroartemisinin-piperaquine versus chloroquine to treat vivax malaria in Afghanistan: an open randomized, non-inferiority, trial. Malar J. 2010 Apr 21;9:105. doi: 10.1186/1475-2875-9-105.