Evaluation of Oral Activated Charcoal on the Ability of an Antimalarial Drug to Kill Parasites in Malian Children With Mild Malaria
- Malaria is caused by small parasites carried by some mosquitoes. People can get malaria if an infected mosquito bites them. Malaria destroys red blood cells. Most malaria is mild, but some children develop severe malaria, which kills about 660,000 people annually. About 9 in 10 who die of malaria are Sub-Saharan African children, most under 5 years old. Scientists can save many lives if they find out how to prevent or relieve severe malaria.
- To know if a common medicine called activated charcoal can reduce severe malaria symptoms.
- Children 2 to 11 years old with mild malaria who live in Kenieroba, Mali.
- For the first 2 days and nights, participants will stay in the hospital.
- They will have their medical history taken, and a physical exam.
- Blood will be drawn from a thin tube inserted in their hand or forearm. This will be done 3 times overall. A drop of blood will be taken from a finger prick 12 times overall.
- An antimalarial drug will be injected into the tube in the arm 4 times. Each time the drug is given, participants will drink a small cup of either water or activated charcoal.
- For the following 3 days, participants will take an antimalarial pill.
- On day 7, participants will visit the hospital. A drop of blood from a finger prick will be tested for malaria parasites.
Drug: Actidose Aqua
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Effect of Oral Activated Charcoal on Parasite Clearance Rates in Response to Intravenous Artesunate in Malian Children With Uncomplicated Plasmodium Falciparum Malaria|
- Serum cytokine levels at 0, 24, and 48 h [ Time Frame: Post patient recruitment ] [ Designated as safety issue: No ]
- To compare parasite clearance half-life in patients treated with oAC + IV AS or IV AS [ Time Frame: Post patient recruitment ] [ Designated as safety issue: No ]
- To assess the safety of adjunct treatment with oAC [ Time Frame: During patient recruitment and treatment ] [ Designated as safety issue: Yes ]
|Study Start Date:||September 2013|
|Estimated Study Completion Date:||March 2016|
|Estimated Primary Completion Date:||March 2016 (Final data collection date for primary outcome measure)|
Experimental: AS + oAC
All children will receive AS 2.4 mg/kg IV at 0 and 12 h, 24 h, and 48 h. Children in the AS+oAC group will be given weight-based doses of oAC (Table 1) at 0, 6, 12, and 18 h.
Drug: Actidose Aqua
Actidose Aqua (oAC)(Paddock Laboratories is sold over the counter in the United States in bottles containing 25 g/120 mL (NDC # 0574-0121-04) or 50 g/240 mL (NDC # 0574-0121-08). oAC is stable at room temperature.Drug: Artesunate
Artesunate (AS) obtained from Guilin Pharma (Shanghai), the only pharmaceutical company GMP pre-qualified by the WHO. The product artesunate for injection + 5% sodium carbonate inj + 0.9% sodium chloride inj will be delivered in vials of 30 mg and 60- mg vials, respectively, and will be dosed at 2.4 mg/kg as recommended for SM treatment by the WHODrug: Amodiaquine
Amodiaquine obtained from Pfizer (Dakar), is provided as 200-mg tablets or syrup (50 10 mg/mL), and will be provided as age-based doses per the manufacturer s directions.
Placebo Comparator: AS only (water)
Children in the AS only group will receive a weight based volume of clean water to drink rather than the oAC
Drug: Actidose Aqua
Actidose Aqua (oAC)(Paddock Laboratories is sold over the counter in the United States in bottles containing 25 g/120 mL (NDC # 0574-0121-04) or 50 g/240 mL (NDC # 0574-0121-08). oAC is stable at room temperature.
While the incidence of Plasmodium falciparum malaria declines (1) the proportion of cases with severe malaria (SM) may increase (2). The mortality associated with SM in endemic countries remains high despite the use of artesunate (AS) (3). Safe, cheap, and effective adjunct therapies preventing the development of, or reducing the mortality from, SM could have considerable and rapid public health impact. We discovered that oral administration of activated charcoal (oAC), a safe treatment for acute poisoning (4), protects mice from experimental cerebral malaria and demonstrated in a randomized controlled trial (RCT) in African adults that oAC is safe and does not interfere with the pharmacokinetics of AS (5). Here, we propose the next step to evaluate the efficacy of adjunct treatment with oAC in Malian children and to explore its mode of action. Before testing adjunct treatment with oAC in children with SM, we will perform an open-label RCT in children with uncomplicated malaria (UM) to demonstrate non-inferiority of intravenous (IV) AS plus adjunct oAC vs. IV AS alone with regards to parasite clearance rate. This study will be conducted in African children, because they are the primary target population for such an intervention. Although the adequate standard-of-care treatment for UM is oral (PO) administration of an artemisinin-based combination therapy (ACT), we will treat participants with IV AS. Like ACT treatment of UM, AS is the WHO-recommended first-line treatment for SM (1). In order for the data obtained from UM cases to be meaningful for our future studies in children with SM, we will administer AS to the UM cases in this trial via the same IV route that is used to administer AS to SM cases. Exploratory objectives include: (i) to compare the kinetics of plasma cytokines in both groups, and (ii) to preserve RNA for gene transcription analysis for future studies into the mode of action of oAC. The study will be nested within an NIAID-funded study (Principal Investigators Drs. Fairhurst, Diakite) that assesses parasite clearance rates in response to AS treatment in Kenieroba (6). Children aged 2-10 years with UM and initial parasite densities 10,000 70,000 parasites per micro L will be enrolled. Parasite clearance rates will be expressed as the parasite half-life (Ph), estimated from parasite clearance curves using a formula that has been validated in this cohort (7). Children will be randomized 1:1 to receive IV AS+oAC or IV AS only, respectively, until complete specimen and data sets for 35 children per group are obtained. oAC will be administered as Actidose Aqua[registered] at 0, 6, 12, and 18 hours. AS will be administered IV following WHO recommendations for use of AS in SM (8), followed by 3 daily doses of amodiaquine (AQ). Subsequently and in a separate study, we plan a proof-of-concept RCT to determine whether adjunct oAC reduces disease severity and morbidity (assessed by scoring systems (9)) in hospitalized children with SM and to define the mode of action of oAC. Since oAC is a licensed, inexpensive drug without sophisticated storage requirements, which has an extremely long shelf life at room temperature and can be given orally or via nasogastric tube at high doses without major side effects (4, 10), this drug has an ideal profile for use at the primary health-care level to reduce mortality from SM, or even prevent the development of SM.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01955382
|Contact: Mahamadou Diakite, Pharm.D.||Not Listed|
|Contact: Rick M Fairhurst, M.D.||(301) firstname.lastname@example.org|
|Universite des Sciencies, Techniques et Technologies de Bamako||Recruiting|
|Principal Investigator:||Rick M Fairhurst, M.D.||National Institute of Allergy and Infectious Diseases (NIAID)|