A Comparative Study of Artekin With Standard Malarial Treatment Regimes in Afghanistan

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Uncomplicated Falciparum Malaria, Vivax Malaria

Intervention / Treatment
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* Drug: Dihydroartemisinin + Piperaquine (Artekin)
* Drug: artesunate-sulphadoxin/pyrimethamine, chloroquine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 3 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Artekin<br>Dihydroartemisinin+ Paperaquine (DHA+PPQ, Artekin) | Drug: Dihydroartemisinin + Piperaquine (Artekin)<br>* An adult dose consists of four doses of two tablets, given at 0, 8, 24 and 48 h. The approximate total adult dose is 6/48 mg/kg (DHA/PPQ). For children, a dose of 1.6/12.8 mg/kg is given at the same time intervals; this dosage will be obtained by dissolving the tablets in 5 ml of water.<br>* Other names: Artekin;|
| Active Comparator: Standard treatment<br>The standard treatment for uncomplicated falciparum and vivax malaria are as follows: Uncomplicated falciparum: artesunate-sulphadoxin/pyrimethamine Vivax malaria: chloroquine | Drug: artesunate-sulphadoxin/pyrimethamine, chloroquine<br>* The standard treatment will be in accordance with that in Afghanistan<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PCR corrected adequate clinical and parasitological response (PCR corrected 'adequate clinical and parasitological response' or ACPR) |  | Day 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Crude or PCR uncorrected ACPR |  | Day 56 | 
| Early treatment failure (failure to clear parasitaemia) |  | 7 days | 
| fever clearance times |  | Days | 
| parasite clearance times with no recrudescence over the observation period |  | days | 
| gametocyte clearance times |  | weeks | 
| Haemoglobin levels on day 14 compared to admission |  | day 14 | 
| safety and tolerability (rate and severity of adverse events) |  | day 56 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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falciparum malaria, vivax malaria, dihydroartemisinin-piperaquine