New combination treatment comparable to WHO-recommended ACT in children with malaria
A new fixed-dose combination regimen had similar safety and efficacy profiles compared with artemether-lumefantrine, a WHO-recommended artemisinin-based combination therapy, or ACT, among children with malaria, according to results of a recent phase 3, randomized controlled trial.
Offianan Andre Toure, MD, PhD, of the malariology department at the Institut Pasteur Côte d'Ivoire, and colleagues said the new regimen, which is administered as a single dose, once daily for 3 days, may improve treatment compliance compared with artemether-lumefantrine, or AL, which is administered twice daily for 3 days and has previously been associated with treatment failure in patients with Plasmodium falciparum.
AL is sold under the trade name Coartem (Novartis).
“ACTs are the WHO-recommended first-line treatment for uncomplicated Plasmodium falciparum malaria. However, it is difficult to administer ACT to infants and small children,” the researchers wrote in Clinical Infectious Diseases. “Therefore, a new fixed-dose combination (FDC) of arterolane maleate (AM) 37.5 mg and piperaquine phosphate (PQP) 187.5 mg dispersible tablet has been formulated with easy administration, which may enhance patient adherence and compliance.”
For the trial, Toure and colleagues randomly assigned 859 patients in India and Africa aged 6 months to 12 years with P. falciparum in a 2:1 ratio to receive dispersible tablets containing AM-PQP (n = 571) or AL (n = 288). The researchers conducted an intent-to-treat (ITT) analysis, which involved all of the study participants, and a per-protocol analysis, which included 546 patients in the AM-PQP arm and 271 patients in the AL arm.
At day 28, the overall cure rate in the PP population was 100% in the AM-PQP arm vs. 98.5% in the AL arm (difference, 1.48%; 95% CI, 0.04%-2.91%). In the ITT population, the cure rate was 96% in the AM-PQP arm and 95.8% in the AL arm (difference, 0.14%; 95% CI, 2.68%-2.95%). Cure rates remained similar at day 42 in the ITT population, with AM-PQP yielding a 94.4% cure rate and AL yielding a 93.1% cure rate. The results correspond with findings from a previous study comparing AM-PQP with AL in an older population of patients aged 12 to 65 years.
The average time to parasite clearance was 24 hours in both treatment arms. Meanwhile, fevers were resolved within approximately 6 hours among patients who received AM-PQP and 12 hours among those who received AL. The incidence of treatment-emergent adverse events was similar (93.5% for AM-PQP vs. 92.7% for AL), and most were “mild” and “resolved without sequelae,” according to the researchers. The most common adverse events included anemia, vomiting and cough. No deaths were reported.
“The results of this trial demonstrated the comparable efficacy and safety of FDC of [AM-PQP] dispersible tablets as compared to [AL] in the treatment of uncomplicated P. falciparum malaria in pediatric patients,” the researchers concluded. “This combination offers and easy-to-administer formulation with once-daily dosing, leading to improved patient convenience and compliance with rapid action.” – by Stephanie Viguers
Disclosures: Toure reports no relevant financial disclosures. Please see the studies for all other authors’ relevant financial disclosures.