Active clinical trials for "Malaria"

The main determinant of primaquine efficacy is the total dose of primaquine administered, rather than the dosing schedule. Previous trials have demonstrated that the standard low dose regimen of primaquine (3.5 mg/kg total) fails to prevent relapses in many different endemic locations. For this reason the 2010 WHO antimalarial guidelines now recommend a high dose regimen of 7 mg/kg (equivalent to an adult dose of 30mg per day), although many countries still recommend lower doses for fear of causing more serious harm to unscreened G6PDd patients. Shorter courses of higher daily doses of primaquine have the potential to improve adherence and thus effectiveness without compromising efficacy. Primaquine also has relatively weak but clinically relevant asexual stage activity against P. vivax so larger daily doses may substantially augment chloroquine's blood stage activity at low levels of resistance. In Thailand directly observed primaquine (1mg/kg/day) administered over 7 days was well tolerated and reduced relapses by day 28 to 4%. This is encouraging but not definitive since many relapses present after one month. Longer follow-up is needed to distinguish whether relapse was prevented or deferred. If the efficacy, tolerability and safety of short-course, high-dose primaquine regimens can be assured across the range of endemic settings, along with reliable point-of-care G6PDd diagnostics, then this new primaquine regimen would be a major advance in malaria treatment improving adherence to and thus the effectiveness of anti-relapse therapy. Due to the long duration of standard primaquine treatment regimens, courses are difficult to supervise, are poorly adhered to and lack effectiveness. This proposed multicentre randomised clinical trial will provide evidence across a variety of endemic settings on the safety and efficacy of high dose-short course primaquine in G6PD normal patients. In a parallel single arm study the investigators will also gather safety data on the use of weekly primaquine in patients with G6PDd. This study aims to generate evidence that will directly inform global public health policy for the radical cure of P. vivax. A better understanding of the risks and benefits of primaquine is crucial in persuading policy makers and clinicians of the importance of the radical cure of vivax malaria that will reduce the parasite reservoir and decrease transmission. The funder is Medical Research Council, UK. Grant number: MRC Reference: MR/K007424/1

The overall aim of this study is two fold: to pilot targeted chemo-elimination of plasmodium falciparum malaria in known areas of artemisinin resistance in South East Asia. to understand the micro-epidemiology of malaria in these areas; chiefly, the prevalence and importance to on-going transmission of sub-clinical p.f malaria infections.

KAE609 will be evaluated primarily for hepatic safety of single and multiple doses in sequential cohorts with increasing doses.This study aims to determine the maximum safe dose of the investigational drug KAE609 in malaria patients.

The antimalarial drugs efficacy and safety study will be conducted in the Clinics and hospital of the Cameroon Development Corporation (CDC) Estates, Tiko Health District, located in a typical forest and rainfall area in the South West Region Cameroon. In this study, 350 children aged 6 months to 5 years who are found to have uncomplicated symptomatic malaria will be enrolled between October 2012 and March 2013. Participants will be randomized to receive one of the following medications. (i) DHA+PQ : dihydroartemisinin, 2.5 mg per kg, plus piperaquine phosphate, 20mg per kg daily for 3 days; (ii) ART LUM : Artemether, 2mg per kg, plus lumefantrine 10mg, twice daily for 3 days; (iii) AS+MQ: artesunate, 4 mg/kg/day, with mefloquine, 8 mg/kg/day orally once a day for 3 days. All study medications will be administered orally The Primary objective of this study are to compare the efficacy, safety and tolerability of orally administered artemether plus lumefantrine (ART+LUM), artesunate plus mefloquine (AS+MQ) and dihydroartemisinin plus piperaquine (DHA+PQ) combinations in the treatment of uncomplicated falciparum malaria in Cameroon in order to provide evidence that can be used to determining the optimum antimalaria treatment policy in Cameroon. The secondary objectives are as follows (i) To valuate the efficacy and safety of artemether plus lumefantrine (ART + LUM) and artesunate plus mefloquine (AS + MQ) versus dihydroartemisinin plus piperaquine (DHA + PQ) combination (ii) To compare the clearance of asexual parasites and gametocytes in each treatment arm (iii) To assess the clearance of fever (iv) Assess effect of each treatment arm on anemia This study is a randomized, double blinded clinical trial. After enrollment, participant will be randomized to one of the three treatment regimen. The treatment outcome will be assessed through a 42-day efficacy study. Participants who will exhibit early or late treatment failure and those with adequate clinical response and parasitological failure on day 14, 28 or 42 will be treated with quinine (25mg base per kg body weight per day in three divided doses for five days). In addition to antimalarial drugs oral paracetamol (50mg/kg body weight per day in three divided doses) will be administered for fever exceeding 37.5%. Polymerase Chain Reaction (PCR) -corrected 28 day and 42 day efficacy will be evaluated for each treatment episode.

The Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM) study is the first placebo-controlled randomized clinical trial of hydroxyurea treatment in a malaria endemic region. NOHARM has now achieved full enrollment; all children have completed the blinded portion of the protocol and are in the open-label study treatment portion. This extension study of maximum tolerated dose (MTD), addresses the next critical set of questions about the optimal dosing and monitoring of hydroxyurea treatment for children with SCA in low-resource settings. By providing guidance about optimal hydroxyurea treatment, the NOHARM MTD Study will directly inform policies that can transform the health of African children living with SCA.

This is a single-centre, open-label, study using induced blood stage malaria (IBSM) infection to characterize the activity of (+)-SJ000557733 or SJ733 for short, against early Plasmodium falciparum blood stage infection. The study will be conducted in two cohorts (n=8 per cohort). The anticipated efficacious dose range is expected to be within a range of 125 to 600 mg. The dose used in the first cohort was determined on the basis of the safety and PK data generated in the FIM study (NCT02661373) currently ongoing in United States (US) and will be 150 mg. Depending on the pharmacodynamics data (effect of SJ733 on parasitaemia) obtained from this first cohort, the dose in Cohort 2 may be adjusted but will not exceed 600 mg. Based on the PK from all three cohort from the FIM study, the median estimated dose to obtain the target SJ733 AUC of 13,000 (ug hr/L) is 370 mg. The dose of cohort 2 (≤600mg) is intended to provide further concentration-response information in the human challenge model. For Cohort 2 only, a second dose of SJ733 may be administered at peak gametocytaemia to assess if SJ733 can reduce gametocytes and subsequent infectivity to mosquitoes (a washout of ~15 days post initial SJ733 treatment will be observed). Depending on the data obtained from the first two cohorts, there may be a subsequent cohort, with the investigated dose of SJ733 to be determined by the Sponsor and Principal Investigator (PI) and endorsed by the Safety Review Team. Should this third dose be investigated, a substantial amendment including preliminary data from the first two cohorts will be submitted to the HREC for approval.

We plan to assess the efficacy of 3 different regimens of chloroquine and primaquine for the treatment of P. vivax infections in Cruzeiro do Sul, Acre, Brazil. Patients will be divided in 3 different groups: treatment with regular dose of primaquine (0.5 mg/kg per day for 7 days) with directly observed therapy; regular dose of primaquine without directly observed therapy; and increased total dose of primaquine (0.5 mg/kg per day for14 days) with directly observed therapy. All patients will receive chloroquine (CQ) for three days at a daily dose of approximately 25 mg/Kg in accordance with the Brazilian National Malaria Control guidelines. Clinical and parasitologic parameters will be monitored over a 28-day follow-up period to evaluate drug efficacy and for a total period of 168 days (24 weeks) to evaluate chances of recrudescence, relapse, or reinfection. Results from this drug efficacy study will be used to assist the Brazilian Ministry of Health in assessing their national malaria treatment policy for P. vivax malaria.

Primary Objective: To show the contribution of artefenomel (OZ439) to the clinical and parasiticidal effect of OZ439/Ferroquine (FQ) combination by analyzing exposure-response of OZ439 measured by Day 28 polymerase chain reaction (PCR)-corrected adequate clinical and parasitological response (ACPR) for the effect and the area under the curve (AUC) of OZ439 as pharmacokinetic (PK) predictor. Secondary Objectives: To evaluate the exposure-response of OZ439 combined with FQ on crude Day 28 ACPR. To evaluate the dose response of OZ439 combined with FQ on PCR-corrected and crude Day 28 ACPR. To evaluate the dose-response of OZ439 combined with FQ on selected secondary endpoints. To evaluate the safety and tolerability of different dosages of OZ439 in combination with FQ and FQ alone. To characterize the PK of OZ439 in plasma, and of FQ and its active metabolite SSR97213 in blood.

This study aims to determine whether a 14 day course of 0.5 mg/kg/day primaquine can eliminate subclinical P. vivax infections detected by high volume ultra-sensitive PCR (uPCR).

Safety of artesunate-amodiaquine combined with methylene blue or primaquine for falciparum malaria treatment in African children: A randomised controlled trial Elimination has become the goal of malaria programmes in an increasing number of endemic countries and regions. As resistance against artemisinin compounds has recently started to emerge in South-East Asia, there is a clear need to develop alternative malaria drug combinations. Adding another anti-malarial with a short half-life such as methylene blue to standard ACT (artemisinin-based combination therapy) could be a strategy to prevent artemisinin resistance development. Moreover, adding a gametocytocidal drug to ACT reduces the probability of transmission of P. falciparum parasites including drug-resistant parasites. Objectives: The primary objective of this trial is to investigate the safety of artesunate (AS) - amodiaquine (AQ) - methylene blue (MB) compared to AS - AQ - primaquine (PQ) in young children with uncomplicated falciparum malaria in Burkina Faso.