TES of Artemether-lumefantrine for Pf in the Philippines in 2017-2018

NCT05958810 | Completed DMC FDA Drug

• 1 other identifier: 2003-25-12_2017
• Study Type: observational
• Target: 80
• Locations: 0 countries
• Sites: N/A

Brief Summary

The emergence and spread of drug resistance is a major obstacle to combating malaria. The World Health Organization (WHO) recommends that regular efficacy monitoring should be undertaken by all malaria endemic countries that have deployed artemisinin combination therapy (ACT), to help early detection of drug resistant strains of the parasite and contain their rapid spread. Artemether-lumefantrine (AL) has been the first-line antimalarial drug against uncomplicated Plasmodium falciparum malaria in the Philippines since 2009, with primaquine as an anti-relapse drug. The objective of this study is to assess the safety and efficacy of artemether-lumefantrine for the treatment of uncomplicated P. falciparum infections in the Philippines. The study was conducted in three (3) municipalities (Bataraza, Brooke's Point, and Rizal) of Palawan. Single-arm prospective study of a 28-day follow-up was conducted from February 2017 to December 2018 according to the revised WHO 2014 drug efficacy study protocol. Study subjects were consenting individuals seeking care at the selected Rural Health Units, who were aged \>6 months old to 59 years old with confirmed uncomplicated P. falciparum infections. AL was administered for 3 days according to body weight (Days 0, 1 and 2) and primaquine 0.75 mg/kg body weight single dose was given on Day 3 following the National Treatment Guidelines.

Conditions

Malaria,Falciparum; Malaria Recrudescence

Keywords

Malaria; TES; Artemether-lumefantrine

Outcome Measures

Primary Outcomes (4)

• Number of Patients with Early Treatment Failure (ETF)

  The number of patients with the following criteria based on microscopy results without PCR: * Development of danger signs or severe malaria on day 1, day 2, or day 3 in the presence of parasitemia; * Parasitaemia on day 2 higher than day 0 count irrespective of axillary temperature; * Parasitaemia on day 3 with axillary temperature ≥37.5 ºC; * Parasitaemia on day 3 ≥25% of count on day 0.

  Day 1-3

• Late Clinical Failure (LCF)

  The number of patients with the following criteria based on microscopy results without PCR: * Development of danger signs or severe malaria on any day from day 4 to day 28 in the presence of parasitemia, without previously meeting any of the criteria of Early Treatment Failure; * Presence of parasitemia and axillary temperature ≥37.5 ºC (or history of fever in low/moderate transmission areas) on any day from day 4 to day 28, without previously meeting any of the criteria of Early Treatment Failure.

  Day 4-28

• Number of Patients with Late Parasitological Failure (LPF)

  The number of patients with the presence of parasitemia on any day from day 7 to day 28 and axillary temperature \<37.5 ºC, without previously meeting any of the criteria of Early Treatment Failure or Late Clinical Failure.

  Day 7-28

• Number of Patients with Adequate Clinical and Parasitological Response (ACPR)

  The number of patients with absence of parasitemia on day 28 irrespective of axillary temperature without previously meeting any of the criteria of Early Treatment Failure or Late Clinical Failure or Late Parasitological Failure.

  Day 0-28

Study Arms (1)

Patients detected with Plasmodium falciparum (Artemether-lumefantrine)

Patients with mono-infection of Plasmodium falciparum with 1,000-100,000 asexual forms per µl

Drug: Artemether-lumefantrine; Drug: Primaquine

Interventions

Artemether-lumefantrine DRUG

Artemether-lumefantrine will be administered for 3 days according to body weight (Days 0 and 8 hours after, 1 and 2). Dosage depending on body weight or age if weight cannot be determined. Dosage: 1 tablet contains 20 mg artemether and 120 mg lumefantrine Dosage per weight: 1 tablet (5 to \<16kg); 2 tablets (15 to \<25kg); 3 tablets (25 to \<35kg), 4 tablets for \>35 kg) Dosage per age, if weight cannot be determined: 1 tablet (6 months old to 3 years old); 2 tablets (4 to 8 years old); 3 tablets (9-13 years old), 4 tablets (\>13 years old)

Also known as: Coartem

Patients detected with Plasmodium falciparum (Artemether-lumefantrine)

Primaquine DRUG

For Pf patients, primaquine at 0.75 mg base/kg body weight single dose will be given on Day 3 for Pf patients; For Pv patients primaquine will be withheld for 28 days and will be given after Day 28 follow-up, at 0.25 mg base/kg per day for 14 days.

Patients detected with Plasmodium falciparum (Artemether-lumefantrine)

Eligibility Criteria

• Age: 6 Months - 59 Years
• Sex: all
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The population of interest consists of patients aged between \> 6 months to 59 years old diagnosed with uncomplicated falciparum malaria attending the study health clinic, and having given, or whose parents or legal guardians have given informed consent for study inclusion and assent in children as appropriate.

You may qualify if:

• Above 6 months old to 59 years old;
• Mono-infection with P. falciparum (1000-100 000 asexual forms per µl)
• Axillary temperature ≥37.5 °C or oral/rectal temperature of ≥38 °C;
• Ability to swallow medication;
• Ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule;
• Informed consent from the patient or from a parent or legal guardian in the case of children less than 18 years old;
• Informed assent from any minor participant aged 12 - 17 years;
• Consent for pregnancy testing from females of child-bearing potential and from their parent or guardian if under 18 years old.

You may not qualify if:

• Presence of general danger signs among children \<5 years old or other signs of severe and complicated falciparum malaria according to current WHO definitions
• Mixed Plasmodium species;
• Presence of severe malnutrition
• Presence of febrile conditions due to diseases other than malaria (measles, acute lower tract respiratory infection, severe diarrhea with dehydration, etc.), or other known underlying chronic or severe diseases (e.g. cardiac, renal, hepatic diseases, HIV/AIDS)
• History of hypersensitivity reactions to any of the drug(s) being tested or used as alternative treatment.

Sponsors & Collaborators

• Research Institute for Tropical Medicine, Philippines: lead
• World Health Organization: collaborator

Related Publications (2)

• Council for International Organizations of Medical Sciences. International ethical guidelines for biomedical research involving human subjects. Bull Med Ethics. 2002 Oct;(182):17-23.

  PMID: 14983848 BACKGROUND

• World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013 Nov 27;310(20):2191-4. doi: 10.1001/jama.2013.281053. No abstract available.

  PMID: 24141714 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Capillary blood (malaria blood film and filter paper)

MeSH Terms

Conditions

Malaria, Falciparum; Malaria

Interventions

Artemether, Lumefantrine Drug Combination; Primaquine

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; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Fe Esperanza Caridad J Espino, MD, PhD

  Research Institute for Tropical Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Specialist IV, Principal Investigator, Head of Parasitology Department

Study Record Dates

• First Submitted: June 30, 2023
• First Posted: July 25, 2023
• Study Start: January 2, 2017
• Primary Completion: December 28, 2018
• Study Completion: December 28, 2018
• Last Updated: July 25, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data information will be provided upon request
• Access Criteria: Data Transfer