Efficacy of Antimalarial Drugs Used for the Treatment of Uncomplicated Malaria, Plasmodium Falciparum, at the Agadez, Gaya and Tessaoua Sentinel Sites

NCT05070520 | Completed Phase 4

• 1 other identifier: 033/2020/CNERS
• Study Type: interventional
• Target: 259
• Locations: 1 country
• Sites: 1

Brief Summary

In Niger, malaria is a major public health problem. It is the main cause of morbidity and mortality among children. The management of malaria cases is based on the principle of early diagnosis and rapid treatment with effective drugs. It is confronted with the appearance of strains resistant to antimalarial drugs, hence the need to monitor antimalarial drug sensitivity. The study was conducted in three regions representing epidemiological strata of the country: Agadez (Centre de santé Intégré of Dagamanet in the Health district of Agadez), Maradi (Centre de santé intégré of Guindaoua in Tessaoua) and Dosso (Centre de santé Intégré centre in Gaya). The protocol used is the WHO standardized protocol of 2009. Artemether/Lumefantrine (AL) was administered with a 28-day follow-up in children aged 3 months to 15 years. A Polymerase Chain Reaction (PCR) correction is planned to differentiate between treatment failure and re-infestation as well as a study of genes responsible for resistance on the main drugs used.

Conditions

MALARIA

Keywords

Malaria; Efficacy; Arthemeter; Lumefantrine; Niger

Outcome Measures

Primary Outcomes (12)

• Percentage of patients with asexual falciparum parasitaemia on Day 0.

  Parasitaemia always refers to falciparum species. Mixed infections detected by light microscopy was excluded.

  4 weeks

• Number of patiants with presence of gametocytes on Day 0

  4 weeks

• Percentage of patients with danger signs of malaria on Day 1

  Depending on the classification, a patient will be considered as having experienced treatment failure if the danger signs are associated with the presence of parasites.

  4 weeks

• Proportion of patients with 'adequate clinical and parasitological response' (ACPR) before PCR-corrected

  absence of parasitaemia on day 28 (day 42), irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure

  8 weeks

• Proportion of patients with 'adequate clinical and parasitological response' (ACPR) after PCR-corrected

  PCR analysis

  24 weeks

• Proportion of patients with 'early treatment failure' (ETF) before PCR-corrected

  * Danger signs or severe malaria on day 1, 2 or 3, in the presence of parasitaemia; * Parasitaemia on day 2 higher than on day 0, irrespective of axillary temperature; * Parasitaemia on day 3 with axillary temperature ≥ 37.5 °C; and * Parasitaemia on day 3 ≥ 25% of count on day 0

  8 weeks

• Proportion of patients with 'early treatment failure' (ETF) after PCR-corrected

  -PCR analysis

  24 weeks

• Proportion of patients with 'late clinical failure' (LCF) before PCR-corrected

  * danger signs or severe malaria in the presence of parasitaemia on any day between day 4 and day 28 (day 42) in patients who did not previously meet any of the criteria of early treatment failure; and * presence of parasitaemia on any day between day 4 and day 28 (day 42) with axillary temperature ≥ 37.5 °C in patients who did not previously meet any of the criteria of early treatment failure

  8 weeks

• Proportion of patients with 'late clinical failure' (LCF) after PCR-corrected

  PCR analysis

  24 weeks

• Proportion of patients with 'late parasitological failure' (LPF) before PCR-corrected

  presence of parasitaemia on any day between day 7 and day 28 (day 42) with axillary temperature \< 37.5 °C in patients who did not previously meet any of the criteria of early treatment failure or late clinical failure.

  8 weeks

• Proportion of patients with 'late parasitological failure' (LPF) after PCR-corrected

  PCR analysis

  24 weeks

• Percentage of the known mutations associated with artemisinin resistance observed.

  PCR analysis

  24 weeks

Interventions

Artemether-lumefantrine DRUG

Efficacy of artemether lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in three sentinel sites in Niger (Agadez, Gaya and Tessaoua) in 2020

Eligibility Criteria

• Age: 3 Months - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Brachial circumference (BC) \> 125 mm and P/T z-score \> -2 Standard Deviation (SD)
• Age between three months and fifteen years,
• Monospecific Plasmodium falciparum infestation detected by microscopy;
• Parasitemia between 1000 and 200000 asexual parasitic forms/µl ;
• Axillary temperature ≥37.5° or history of fever in the past 24 hours ;
• Ability to take oral medications;
• Ability and willingness to adhere to the protocol for the duration of the study and to adhere to the visit schedule ;
• Informed consent of the accompanying person (guardian or parent).

You may not qualify if:

• Inability to take oral medications
• History of antimalarial treatment in the past two weeks, including sulfadoxine-pyrimethamine (SPAQ) for seasonal malaria chemoprevention (SMC)
• Lack of consent for pregnancy testing
• Presence of general danger signs in children under five years of age or signs of severe P. falciparum malaria as defined by World Health Organization (WHO);
• Mixed infestation or monospecific infestation with another Plasmodium species, detected by microscopic examination;
• Severe malnutrition defined by a BC \<125 mm AND P/T z-score \< -3 Standard Deviation (SD)
• Moderate malnutrition defined by a BC \<125 mm AND a -3 ≤P/T z-score \< -2 SD
• Febrile condition due to illnesses other than malaria (e.g., measles, acute lower respiratory tract infection, severe diarrheal illness with dehydration) or other known chronic or severe underlying illnesses (e.g., cardiac, renal, or liver disease, HIV/AIDS) ;
• Regular use of medications that may interfere with antimalarial pharmacokinetics;
• History of hypersensitivity or contraindication to any of the drugs tested or used as replacement therapy;
• Lack of informed consent from the patient or accompanying person

Sponsors & Collaborators

• Programme National de Lutte contre le Paludisme, Niger: lead

Study Sites (1)

Programme National de Lutte Contre Le Paludisme

Niamey, 00227, Niger

Location

Related Publications (2)

• Severe falciparum malaria. World Health Organization, Communicable Diseases Cluster. Trans R Soc Trop Med Hyg. 2000 Apr;94 Suppl 1:S1-90. No abstract available.

  PMID: 11103309 RESULT

• Laminou IM, Issa I, Adehossi E, Maman K, Jackou H, Coulibaly E, Tohon ZB, Ahmed J, Sanoussi E, Koko D. Therapeutic efficacy and tolerability of artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria in Niger, 2020. Malar J. 2024 May 13;23(1):144. doi: 10.1186/s12936-024-04945-8.

  PMID: 38741101 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Hadiza JACKOU, Dr

  PROGRAMME NATIONAL DE LUTTE CONTRE LE PALUDISME

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: This surveillance study is a prospective one-arm evaluation of clinical and parasitological responses to treatment of uncomplicated malaria with direct observation of treatment. Individuals with uncomplicated malaria, who meet the study inclusion criteria, will be recruited and treated at the sites by AL. They will be monitored for 28 days. Follow-up will consist of a series of fixed-date monitoring visits and corresponding clinical examinations and laboratory tests. Based on the results of these assessments, patients will be classified as having treatment failure (early or late) or adequate response. The proportion of patients with treatment failure during follow-up will be used to assess the efficacy of the study drugs. PCR analysis will be used to distinguish between true recrudescence due to treatment failure and episodes of re-infestation. A proportion of 10% of the slides read in the field will be submitted for quality control.

Study Record Dates

• First Submitted: September 24, 2021
• First Posted: October 7, 2021
• Study Start: September 1, 2020
• Primary Completion: September 30, 2020
• Study Completion: October 28, 2020
• Last Updated: October 7, 2021

Record last verified: 2021-10

Locations

NI (1)