An Open Label Randomized Comparative Study to Assess the Efficacy and Tolerability of Eurartesim® Versus Chloroquine and Nonrelapse Therapy With Primaquine for Uncomplicated Plasmodium Vivax Monoinfection Malaria

CAAE: 69476017.3.0000.0005

Plasmodium vivax can be cause of severe malaria and mortality. There are serious public health implications associated with cases of P. vivax resistant to Chloroquine in the Americas as well there are efforts of many countries to eliminate this disease. In this way, it is critically important to evaluate an alternative radical cure treatment efficient to amazon scenario. The objectives of this trial are to demonstrate the superiority of adequate parasitological response at D42 of Dihydroartemisinin plus Piperaquine (DHA-PQP or Eurartesim®) versus Chloroquine and to evaluate the proportion of failure until D180 considering different starting days of Primaquine (0.50 mg/kg/day) for 14 days. It is an open, 4 arms, randomised, comparative trial. Total of 460 patients are initially planned to be included. To demonstrate the superiority of DHA-PQP compared to Chloroquine, the 95% confidence interval of the difference observed between both treatment success rates will be determined. Each recurrence will be passively and actively detected for 180 days.

2018-07-05

2021-07-02

2021-07-02

Completed

Early phase I

419

1 Inclusion criteria: 1. Adults and children over 6 months old (bodyweight\>5 kg) 2. Body weight ≥5 kg and \<100 kg (or above, upon justification of the investigator); 3. Biologically confirmed symptomatic Monoinfection by Plasmodium vivax, with parasite density between 100 and 100,000; 4. Efficient activity of the enzyme Glucose-6-Phosphate Dehydrogenase (G6PD); 5. Conditions for oral treatment; 6. Plans known to remain in the area of the research center during the follow-up period (180 days); 7. Hemoglobin concentration (Hb) at baseline\> 7g / dL. 8. Women with reproductive potential (defined as women who are not in postmenopausal dust for at least 24 consecutive months, ie without menstruation within 24 months of admission to the study, and women who have not undergone surgical sterilization, specifically hysterectomy or bilateral oophorectomy) must have a negative pregnancy test or urine test within 48 hours prior to admission to the study; NOTE: The history reported by the participant is considered acceptable documentation of hysterectomy, bilateral oophorectomy, and menopause. Women are considered menopausal if they have not had a menstrual period for at least 12 months and have had a follicle-stimulating hormone (FSH) greater than 40 IU/L; if the FSH test not available, they must be in amenorrhea for 24 or more consecutive months. For women of child-bearing age, provision is made for using contraceptives as described in research product and primaquine information. Contraceptives should preferably be used at least two weeks prior to the start of study drug and continued for least one week after the discontinuation of any drug from the study. In case the patient reports that she has not used any contraceptive method in the two weeks prior to inclusion, she may be included if the doctor discards the possibility of pregnancy; 9. If the patient engage in sexual activity that could lead to pregnancy, women should use a form of contraception. At least one of the following methods should be used properly: Condoms (male or female) with or without spermicidal agent; Diaphragm or cervical cap with spermicide Intrauterine device (IUD) Hormonal contraceptive Ligation Tubal microimplants i. Women with no reproductive potential, as defined above, are without the use of contraceptives. j. Ability and willingness of the participant or legal guardian to provide free and informed consent in writing. Children who are able to understand the goals and risks of the study will sign a consent form. 2. Non-inclusion criteria: a. Participate in another ongoing clinical trial; b. Signs of severe malaria such as: recent history of seizures (1-2 within 24 hours), unconscious state, lethargy, inability to drink or breastfeed, constant vomiting, inability to get up / sit due to weakness; c. Known hypersensitivity to any of the experimental medicinal products or to any of the excipients d. Evidence or report of ingestion of antimalarial treatment in the 60 days prior to inclusion; e. Concomitant or underlying serious illness, such as porphyria or psoriasis or known disturbances of electrolyte balance, such as hypokalemia or hypomagnesemia; f. Liver function test with ALT\> 3x the reference value, which, according to the researcher's assessment, endangers the safety of the participant; 3. Exclusion criteria: 1. Withdrawal of consent; 2. The researcher's opinion, based on the risk and benefit assessment of the study; 3. Detection of mixed infection by malaria; 4. Women who become pregnant by the 63rd day of follow-up; 5. Women of childbearing age who give up using effective contraception during the first 63 days of follow-up study; 6. Discontinuation of blood schizonticidal treatment for any reason.

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2023-06-12