Active clinical trials for "Malaria, Falciparum"

Malaria is caused by protozoan parasites of the genus Plasmodium and it is the most important parasitic disease in terms of mortality and morbidity. Estimates of 247 million malaria cases and 619.000 deaths worldwide were reported by WHO for the year 2021 (1). Plasmodium falciparum can lead to severe malaria and accounts for 90% of malaria deaths that mainly occur in children below the age of 5 years in Sub-Saharan Africa. A simplified treatment regimen, ideally a single-day cure (or at most 2-day dosing regimen), of uncomplicated malaria due to P. falciparum would be the magic in the antimalarial armamentarium. Improving treatment adherence is one of the key factors in reducing mortality and morbidity and also the transmission of malaria, and such a regimen would substantially increase adherence. To find a new non-artemisinin combination therapy with a shorter regimen, ideally, a single-dose cure, with low resistance potential would be the aim. The two compounds tested here are ZY19489, a triaminopyrimidine, and ferroquine (FQ), a next-generation 4-aminoquinoline. Both compounds show unique features in terms of long half-life, and activity against current drug-resistant strains. Therefore, the main goal of this clinical trial is to assess the safety of the ZY19489-FQ combination given as a 1- or 2-day dose regimen.

Mozambique is among the ten countries with the highest burden of malaria worldwide, with an estimated 9.3 million cases in 2018, and constitutes a core target for the World Health Organization (WHO) and the Roll Back Malaria Partnership to End Malaria's country-led 'high burden to high impact' initiative. At the same time, the National Malaria Control Program (NMCP) of Mozambique seeks to accelerate elimination in the south, where transmission is lowest. NMCP is currently working with partners (Malaria Consortium, PMI, Global Fund) to set up a high-resolution surveillance system that can drive decision-making across all transmission strata through strengthening of routine data quality, data use and data to action packages. However, decisions become more complex as control reveals heterogeneity and better tools are required for a strategic use of information to drive impact. The overall objective of the study is to operationalize a functional malaria molecular surveillance (MMS) system that generates reliable and reproducible genomic data over time for programmatic decisions. The integration of genomic data into routine surveillance activities has the potential to increase the actionable intelligence for making programmatic decisions on the optimal mix of control and elimination measures in Mozambique by: Informing drug and diagnostic choices through the monitoring of antimalarial drug resistance and diagnostic resistance (hrp2/3 deletions); Targeting the reservoirs sustaining transmission through the use of transmission network models to quantify parasite importation, identify sources and characterize local transmission in near-elimination settings; Improving stratification, monitoring and impact evaluations in different epidemiological and health system contexts through the use of measures of P. falciparum genetic diversity (routinely from positive cases) to supplement traditional surveillance, especially where it is sparse; Using alternative, cost-effective, approaches targeting easy-access populations (e.g. pregnant women at antenatal care clinics) to monitor transmission and antimalarial/diagnostic resistance.

The aim of this study is to investigate if diabetes, obesity and metabolic syndrome affects disease presentation and severity of malaria in adults in a hospital setting in Cameroon.

Lactating women requiring treatment for uncomplicated malaria will be identified and invited for sampling. The decision to treat them with first-line treatment will have been made by the clinician, not by a member of the study team. The study team will not make any adjustments to the prescribed treatment. Artemether-lumefantrine comprises six doses of medication, with the initial two doses given 8 hours apart on Day 1, and dosing 12-hourly on Day 2 and Day 3. Intensive pharmacokinetic sampling will be undertaken after Dose 5, as indicated in the schema under Section 5: plasma and breastmilk samples will be obtained pre-dose and at 2, 4, 6, 8 hours after dose. In addition, sparse sampling will be undertaken on either of these occasions; at pre-dose and between 1 to 6 hours after the first dose; a trough (pre-dose) sample after the Dose 3 or Dose 4 and lastly at 5, 7, and up to 14-days after the first dose. A heelprick sample will also be obtained from the breastfed infants at maternal trough (prior to maternal dose) and at a random timepoint (once per infant) over the 8-hour pharmacokinetic sampling visit to characterize concentrations of these drugs over an 8-hour dosing interval. In addition, a single heelprick sample will be obtained from the infant whenever the mother returns after treatment for the late sampling time points (5, 7, and 14 days post the first dose). Due to the long half-life of lumefantrine of approximately 6 days plasma sampling will be performed up to day 14 to characterise the terminal elimination of the drug. Concentrations of total plasma and breastmilk lumefantrine and desbutyl-lumefantrine will be determined.

This is to develop a model to test the efficacy of vaccines and/or drugs designed to block transmission of malaria to mosquitoes and to identify the targets of transmission-blocking immunity to malaria.

This is an open i.e. not blinded, cluster-randomised, controlled intervention study. The study will use a factorial design to estimate the protective effectiveness of mass drug administrations, mass vaccinations, combined mass vaccinations and drug administrations versus the current standard of care.

Background: Mortality from severe malaria remains ~15% despite the use of the most rapidly parasiticidal antimalarial therapy, artesunate. Adjunctive treatments may improve outcome. Our overall goal is to determine if adjunctive treatment with L-arginine is safe and improves outcomes in severe malaria. In studies to date, we have shown that L-arginine is safe in moderately severe malaria, increases nitric oxide production and improves endothelial function. We now propose to extend these studies to patients with severe malaria. Aims: To determine the safety, preliminary efficacy, pharmacokinetics and pharmacodynamics of L-arginine infusion in severe malaria. Hypothesis: L-arginine will improve endothelial function, lactate clearance time and tissue oxygen delivery compared to saline with no clinically significant adverse effects. Methods: Based on previous pharmacokinetic modeling and simulations, we propose a phase 2A randomised controlled trial of L-arginine vs saline in severe malaria, each given over 8 hours. If safety is demonstrated this will be followed by a phase 2B open-label study of 24-hour infusion of L-arginine in severe malaria with safety and preliminary efficacy compared with the 8 hour infusions given in phase 2A. The primary outcomes will be the improvement in endothelial function and lactate clearance in patients given L-arginine infusion compared with those who received saline. Among the secondary outcomes will be safety and the effect of L-arginine vs saline on tissue oxygen delivery (NIRS). Data from both phase 2A and 2B will be used to generate a pharmacokinetic/ pharmacodynamic model.

This is a two-arm, open label Treatment Study comparing the efficacy, safety, tolerability and pharmacokinetics of a three-day course of Dihydroartemisinin-Piperaquine (DP) with or without single-dose primaquine in patients with uncomplicated Plasmodium falciparum malaria. On the last day of DP therapy, volunteers will be randomized to receive either a single 45 mg dose of primaquine (PQ) or DP treatment only (no primaquine).

In camps for displaced persons located along the Thai-Myanmar border, mefloquine and artesunate combination therapy has been used since 1992. In vivo efficacy of a 3 day regimen of mefloquine + artesunate (MAS3) has been monitored regularly since its introduction in 1992. In 2009 Carrara et al summarised the in vivo PCR-adjusted cure rates at Day 42 and Day 63 in patients treated with MAS3 between 1995 and 2005, as well as the in-vitro parasite susceptibility to MAS3 during that same period, and the changes in pfmdr1 copy numbers.The proportion of patients with parasitaemia persisting on day-2 increased significantly from 4.5% before 2001 to 21.9% after 2002 (p<0.001). Delayed parasite clearance was associated with increased risk of developing gametocytaemia (AOR = 2.29; 95% CI, 2.00-2.69, p = 0.002). MAS3 efficacy declined slightly but significantly (Hazards ratio 1.13; 95% CI, 1.07-1.19, p<0.001), although efficacy in 2007 remained well within acceptable limits: 96.5% (95% CI, 91.0-98.7). The proportion of infections caused by parasites with increased pfmdr1 copy number rose from 30% (12/40) in 1996 to 53% (24/45) in 2006 (p = 0.012, test for trend). Evidence of reduced susceptibility to artemisinins in Western Cambodia was first reported in January 2007. Artemisinin resistance was manifest by a marked slowing of parasite clearance. A more recent analysis of parasite clearance data collected prospectively in patients with uncomplicated hyperparasitaemic malaria has shown a progressive decline in parasite clearance rates over the last decade suggesting a decline following the same trajectory as in Western Cambodia but with a time lag of a few years. Surveillance data collected in 2011 have shown a dramatic and worrying decline in efficacy of MAS3, albeit in a small number of patients. This decline in efficacy of mefloquine + artesunate is likely to be attributable to reduced parasite susceptibility to mefloquine. The other fixed dose combinations available dihydroartemisinin-piperaquine (DP) is the best option to replace mefloquine-artesunate since it is thought that it remains effective in the presence of high pfmdr1 copy numbers. In addition DP is administered once daily and needs no special dietary modification to ensure adequate absorption. In this study it is hypothesised that efficacy of DP (estimated to be 95%) will be significantly higher than that of MAS3 (estimated to be 65%), therefore the investigators propose to conduct a randomised controlled trial between DP and MAS3 for the treatment of P.falciparum.

The purpose of this study is to determine the tolerability and pharmacokinetics of Sevuparin/DF02 when administered as an i.v. infusion in combination with Malanil® (atovaquone/proguanil) as anti-malarial treatment in subjects affected with uncomplicated malaria. The study will also assess the potential of Sevupatin/DF02 to reduce infected erythrocyte sequestration and rosette formation. The study consists of a dose escalation part (part 1) followed by an open labelled, randomized comparison of treatment with Sevuparin/DF02 and Malanil® versus Malanil® alone (part 2).