Safety and tolerability of artesunate-amodiaquine, artemether-lumefantrine and quinine plus clindamycin in the treatment of uncomplicated Plasmodium falciparum malaria in Kinshasa, the Democratic Republic of the Congo


Autoři: Yves Lula Ntamba aff001;  Hypolite Muhindo Mavoko aff002;  Marion Kalabuanga aff004;  Blaise Fungula aff004;  Pierre-Michel Ntamabyaliro Nsengi aff001;  Gaston Tona Lutete aff001;  Raquel Inocencio da Luz aff002;  Jean-Pierre Van geertruyden aff002;  Pascal Lutumba aff003
Působiště autorů: Clinical Pharmacology and Pharmacovigilance Unit, University of Kinshasa, Kinshasa, Democratic Republic of the Congo aff001;  Global Health Institute, Faculty of Medicine, University of Antwerp, Antwerp, Belgium aff002;  Department of Tropical Medicine, University of Kinshasa, Kinshasa, Democratic Republic of the Congo aff003;  Lisungi Health Centre, Kinshasa, Democratic Republic of the Congo aff004
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0222379

Souhrn

Introduction

Artemisinin-based combination therapy is currently the best option for the treatment of uncomplicated malaria. Quinine is recommended as a rescue treatment. Safety information during repeated treatment with the same drug is scarce. We report safety data from the Quinact randomized clinical trial (RCT) that was designed to assess efficacy and safety of artesunate-amodiaquine (ASAQ), artemether-lumefantrine (AL) and quinine+clindamycin (QnC).

Methodology

Males and females aged 12 to 59 months with uncomplicated malaria were treated with ASAQ and followed up during 42 days (preRCT). Clinical failures were randomized to one of the 3 treatments and followed up for 28 days (RCT). Subsequent failures were repeatedly treated with ASAQ several times as needed (postRCT1, postRCT2 and so on) until a 28-days follow up period without parasitaemia.

Results

Eight hundred and sixty-five, 242 and 64 patients were recruited respectively in preRCT, RCT and postRCTs. In preRCT, 433 (50.0%) patients experienced at least one drug-related adverse event (AE). The most reported AEs were anorexia (22.9%), asthenia (19.4%), and abnormal behavior (14.6%). Twenty-nine AEs (3.5%) were reported to be severe. In RCT, at least one drug-related AE was reported in 54.7%, 21.5% and 40.0% of patient randomized respectively to ASAQ, AL and QnC (p<0.001). During postRCT1 (n = 64), postRCT 2 (n = 17) and postRCT3 (n = 7), respectively 32.8%, 35.3% and 71.4% of patients experienced at least one drug-related AE. Three serious adverse events occurred but not judged related to study medication.

Conclusion

The proportion of AEs did not increase over the treatment courses with ASAQ. However, continuous monitoring is important.

Klíčová slova:

Medicine and health sciences – Parasitic diseases – Malaria – Tropical diseases – Pharmacology – Drugs – Antimalarials – Amodiaquine – Drug research and development – Randomized controlled trials – Mental health and psychiatry – Eating disorders – Anorexia nervosa – Clinical medicine – Clinical trials – Hematology – anémia – Diagnostic medicine – Signs and symptoms – Pathology and laboratory medicine – Research and analysis methods – Research design – Clinical research design – Adverse events – Biology and life sciences – Physiology – Physiological processes – Coughing


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