TES of Artemether-lumefantrine for Pf and Chloroquine for Pv in the Philippines From 2013-2014

NCT04222088 | Completed Results DMC FDA Drug

• 1 other identifier: 2003-25-12_2013
• Study Type: observational
• Target: 159
• Locations: 0 countries
• Sites: N/A

Brief Summary

An antimalarial drug efficacy trial was conducted for artemether-lumefantrine (AL) and chloroquine (CQ) in the three (3) municipalities (Bataraza, Brookes and Rizal) of Palawan. Study subjects are febrile individuals between \> 6 months old and 59 years old with confirmed uncomplicated P. falciparum or P. vivax infections. Patients with P. falciparum was treated with Artemether-lumefantrine administered 3 days (Days 0, 1 and 2) according to body weight. Primaquine at 0.75 mg base/kg body weight single dose was given on Day 3. For Plasmodium vivax patients chloroquine were administered according to body weight at a total dose of 25 mg/kg over 3 days (10 mg/kg on Day 0; 10 mg/kg on Day 1 and 5 mg/kg on Day 2), and primaquine following the National Treatment Guidelines. During the period that this report covers, 84 and 75 patients met the inclusion criteria for Pf and Pv respectively. Clinical and parasitological parameters were monitored over a 28-day follow-up period for both drugs. The presence of only 1 Late Clinical Failure (LCF) of P. falciparum parasitemia out of 84 enrolled patients and 2 Late Parasitological Failure (LPF) of P. vivax patients out of 75 enrolled patients within the 28 days follow up suggest that both drugs are still efficacious.

Conditions

Malaria; Falciparum Malaria; Vivax Malaria; Malaria Recrudescence

Keywords

malaria; TES; Plasmodium falciparum; Artemether-lumefantrine; Plasmodium vivax; Chloroquine

Outcome Measures

Primary Outcomes (4)

• Early Treatment Failure (ETF)

  The classification of treatment outcomes will be based on an assessment of the parasitological and clinical outcomes of antimalarial treatment according to the latest guidelines of WHO. Accordingly, all patients will be classified as having an Early Treatment Failure by microscopy results P without PCR correction * 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)

  Patients with late clinical failure without PCR correction: * Development of danger signs or severe malaria on any day from day 4 to day 28 in the presence of parasitaemia, 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

• Late Parasitological Failure (LPF)

  Patients with late parasitological failure without PCR correction: • 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 to day 28

• Adequate Clinical and Parasitological Response (ACPR)

  Adequate Clinical and Parasitological Response (ACPR): 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 (2)

Patients detected with Plasmodium falciparum (Artemether-lumefantrine)

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

Drug: Arthemeter-lumefantrine; Drug: Primaquine

Patients detected with Plasmodium vivax (Chloroquine)

Patients with mono-infection of Plasmodium falciparum with ≥ 250 per µl

Drug: Chloroquine; Drug: Primaquine

Interventions

Arthemeter-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)

Chloroquine DRUG

Chloroquine will be administered according to body weight at a total dose of 25 mg base/kg over 3 days (10 mg base/kg on Day 0; 10 mg base/kg on Day 1 and 5 mg base/kg on Day 2). Correct drug dosage will be determined using the dosing chart (in accordance with national treatment guidelines)

Patients detected with Plasmodium vivax (Chloroquine)

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); Patients detected with Plasmodium vivax (Chloroquine)

Eligibility Criteria

• Age: 6 Months - 59 Years
• Sex: all
• Healthy Volunteers: No
• 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 and vivax malaria attending the study health clinic, and having given, or whose parents or legal guardians have given an 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) and P. vivax (≥250/ul)
• Axillary temperature ≥37.5 °C or oral/rectal temperature of ≥38 °C;
• Glucose-6-dehydrogenase (G6PD) test normal for vivax patients if available
• 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; and
• Consent for pregnancy testing from female 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; Malaria, Falciparum; Malaria, Vivax

Interventions

Artemether, Lumefantrine Drug Combination; Chloroquine; 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

Results Point of Contact

• Title: Dr. Fe Esperanza Caridad J. Espino
• Organization: Research Institute for Tropical Medicine

fe.espino2019@gmail.com

63288072628

Study Officials

• Fe Esperanza Caridad J Espino, MD, PhD

  Research Institute for Tropical Medicine, Philippines

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: December 15, 2019
• First Posted: January 9, 2020
• Study Start: May 1, 2013
• Primary Completion: December 30, 2014
• Study Completion: December 30, 2014
• Last Updated: July 21, 2023
• Results First Posted: February 23, 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