Active clinical trials for "Malaria"

The purpose of this study is to study the efficacy of sulfadoxine-pyrimethamine on its own and compare this with efficacy of a new combination antimalarial therapy, either sulphadoxine-pyrimethamine plus artesunate or artemether-lumefantrine.

This is a prospective cohort study where HIV-infected and uninfected children will be enrolled between 6 weeks and 9 months of age and followed to the age of 21 months. All HIV-infected children will be given trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis as of 6 weeks of age. HIV-uninfected children born to HIV-infected mothers will be given TMP/SMX prophylaxis for the duration of breastfeeding and then randomized to the continuation of TMP/SMX or discontinuation of TMP/SMX prophylaxis. HIV-uninfected children born to HIV-uninfected mothers will not be given TMP/SMX prophylaxis. Study participants will be followed for all of their health care needs in a designated study clinic. All mother-child pairs will receive a basic care package including insecticide-treated bednets (ITNs) at enrollment. All HIV-infected mothers and children will receive antiretroviral therapy if eligible according to standardized World Health Organization (WHO) criteria. Study participants 4 months of age or older and at least 5 kg will be randomized to treatment with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) at the time of their first diagnosis of uncomplicated malaria. Study participants will receive the same antimalarial treatment regimen for all future episodes of uncomplicated malaria. Study participants less than 4 months of age or less than 5 kg diagnosed with malaria and all episodes of complicated malaria will be treated with quinine in accordance with local guidelines. The investigators will test the hypotheses that: TMP/SMX prophylaxis is highly effective in preventing malaria in both HIV-infected and HIV-uninfected children The use of TMP/SMX prophylaxis is associated with an increased risk of infection with malaria parasites containing antifolate resistance-conferring mutations. The use of antiretroviral (ARV) drugs is associated with a decreased incidence of malaria. The efficacy, safety, and tolerability of AL and DP for the treatment of uncomplicated malaria differ. In 2008, we received approval and funding to extend the trial until 2012. We are now following all children through 5 years of age. First randomization to continue or discontinue TMP/SMX prophylaxis in our HIV-exposed population occurs 6-8 weeks after cessation of breastfeeding when HIV status can be confirmed as negative by DNA PCR. A second randomization occurs at 2 years of age in our HIV-exposed participants. At that point all HIV-exposed children who were originally randomized to continue TMP/SMX prophylaxis are again randomized to either immediately discontinue TMP/SMX prophylaxis or continue prophylaxis until age 4 years. All children will be off TMP/SMX between 4 and 5 years of age. We have also added an additional hypothesis to test during the study extension: Prolonged TMP/SMX prophylaxis will result in an increased incidence of malaria in children in the year immediately following cessation of prophylaxis compared to children who have not used prophylaxis for over a year and those who have never been on prophylaxis.

The primary objective of the study is to evaluate the effectiveness of 2 intravenous artesunate dosing regimens (2.4 mg/kg initially and at 12, 24, 48, and 72 hours or 4.0 mg/kg initially and at 24 and 48 hours) in clearing P. falciparum parasites in children with severe malaria. Secondary objectives include: To compare the tolerability and safety of the 2 intravenous artesunate dosing regimens. To evaluate differences in the pharmacokinetic profile of intravenous artesunate by patient age and clinical presentation.

The main objective is to compare the safety and efficacy of 4 artemisinin-based combinations (ACT) [amodiaquine-artesunate (AQ+AS), dihydroartemisinin-piperaquine (DHAPQ), artemether-lumefantrine (AL) and chlorproguanil/dapsone plus artesunate] for single and repeat treatments of uncomplicated malaria in children. Safety will be determined by registering adverse events and grading, laboratory, and vital signs evaluations. Their incidence will be compared between the different study arms. TO BE NOTED: following GlaxoSmithKline decision to discontinue the clinical development of the fixed-doses combination of Lapdap (Chlorproguanil-Dapsone) and artesunate, the Lapdap plus Artesunate arm was immediately discontinued in this study, on 17th February 2008. A formal amendment has been submitted to all the concerned ECs and competent authorities. The leading EC approved the amendment on 2nd June 2008. TO BE NOTED: since the batches of the study drug DHAPQ expire at the end of October 2008, and because of the unavailability of a new batch of DHAPQ from the manufacturer, the recruitment in the DHAPQ arm had to be discontinued on 30th October 2008. A formal amendment has been submitted to all the concerned ECs and competent authorities.

The trial will identify the best dose of the synthetic peroxide RBx11160 to treat uncomplicated malaria. Patients will be treated over 7 days with daily doses of 50, 100 or 200 mg RBx11160. The study is designed to assess the antimalarial activity and safety of 3 dose levels of RBx 11160 administered once daily for 7 consecutive days. The primary endpoint will be the time to 90% parasite clearance. In future regulatory studies, RBx 11160 is likely to be administered in combination with another antimalarial agent since the development plan follows the current recommendation of WHO for the treatment of uncomplicated malaria. However, it is critical to gather data on RBx 11160 when used as monotherapy in adult patients suffering from acute uncomplicated P. falciparum malaria. In malaria-endemic regions, an adult population is defined on the basis of immune status rather than the legal age of consent. Thus, patients as young as 13 years of age can be enrolled provided consent has been obtained from a legal guardian in accordance with local practices and regulations. This study will be conducted in compliance with International Conference on Harmonization (ICH) Good Clinical Practice (GCP).

Malaria is a life-threatening disease especially in small children. A high degree of Plasmodium falciparum resistance to chloroquine has already spread to South-Benin where this study is taking place. In the past few years, the recommendation for a first-line treatment in this area has moved from chloroquine to sulfadoxine-pyrimethamine (SP). There is growing evidence that Plasmodium falciparum resistance to SP has come to South-Benin. The aim of the study is to compare the efficacy of SP to two compact artemisinin-based therapies (ACT): artemether-lumefantrine and the amodiaquine-artesunate coformulation. ACT will be unsupervised. The primary endpoint is an effectiveness comparison (PCR corrected) at day 28. Secondary outcomes are effectiveness comparisons (PCR corrected) at day 14 and 42 and a study on the relationships between ACT PK data (day 3) and outcome. Expected total enrollment: 225 patients Study start: April 2007; expected completion: December 2007

The purpose of this study is to test the safety of a 2100 mg dose of AQ-13, a new candidate antimalarial active against drug-resistant P. falciparum infection, and to determine the effect of a standard fatty meal on the absorption of the drug from the gut and its blood levels.

The purpose of this study is to see if providing effective antimalarial treatment at home for parents/guardians to treat their children for malaria will lead to an improved health outcome compared to conventional healthcare.

Lapdap (chlorproguanil-dapsone) is an affordable and effective drug, but patients with glucose-6-phosphate dehydrogenase (G6PD) A- deficiency are more susceptible to the haemolytic effects of the dapsone component of Lapdap; therefore there is a need to evaluate the extent to which the risks associated with the use of the drug in settings without G6PD screening might outweigh the benefits to malaria treatment. The investigators will evaluate, in operational settings, the safety and effectiveness of Lapdap and coartemether (lumefantrine-artemether) for treatment of uncomplicated malaria in patients 6 months to 10 years of age.

The purpose of this trial is to compare the effectiveness of three combination treatments for uncomplicated malaria when given in operational settings, without supervision of doses other than the first dose.