Relapses in Plasmodium Ovale and Efficacy of Artemether-lumefantrine for Mixed Species and Non-falciparum Malaria

NCT02528279 | Completed

• 1 other identifier: Rep001
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

Malaria is a protozoan infection transmitted by anopheline mosquitoes. The most severe forms are caused by Plasmodium (P) falciparum and to a much lesser extent by P. vivax. Although the interest in research on malaria has increased during the last years, yet little research is conducted on the "neglected" malaria species P. ovale and P. malariae. P. ovale being first described in 1922, it still remains unclear whether it displays dormant pre-erythrocytic liver stages, so called hypnozoites, or not. Primaquine, the only marketed drug with liver stage activity at present, can cause severe hemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient persons and methemoglobinemia. Because G6PD is widely spread in Central Africa, it is important to explore whether additional intake of liver-active medication is really needed and on this account further research to investigating new treatment options with liver stage activity should be conducted. While, due to widespread resistance, treatment recommendations for P. falciparum and mixed infections have switched from chloroquine to the safer applicable artemisinin-based combination therapies (ACTs), World Health Organization (WHO) guidelines still suggest chloroquine as first line treatment for P. malariae and P. ovale mono infections. Further studies assessing alternative treatment options are largely missing. Summing up the current situation for both topics shows the need for further research. Therefore this study aims to assess the evidence and characterize the frequency of relapses in P. ovale infections with respect to differences between its subspecies as well as the effectiveness of the ACT artemether-lumefantrine in P. malariae and P. ovale mono- and mixed infections.

Conditions

Malaria

Keywords

Plasmodium ovale; relapse; artemether-lumefantrine; mixed species malaria; non-falciparum malaria

Outcome Measures

Primary Outcomes (1)

• Adequate clinical and parasitological response (WHO criteria for antimalarial drug trials)

  Adequate clinical and parasitological response on Day 28

  28 days

Secondary Outcomes (3)

• Parasite clearance time

  7 days

• Fever clearance time

  7 days

• Reappearance of P. ovale parasitemia

  from day 29 - 2 years of follow up

Study Arms (1)

Coartem

OTHER

Patients will receive the study drug combination artemether-lumefantrine (Coartem®) orally as a 6 dose regimen for three consecutive days. Tablets are available as a fixed dose combination of 20mg artemether plus 120mg lumefantrine. The dosing will be based on the body weight and follow the manufacturer's recommendations: Body weight 5-14kg: 1 tablet; Body weight 15-24kg: 2 tablets; Body weight 25-34kg: 3 tablets; Body weight \> 34kg: 4 tablets; The respective amount of tablets is to be taken at hours 0, 8, 24, 36, 48 and 60 with fatty food.

Drug: Coartem

Interventions

Coartem DRUG

Patients will receive the study drug combination artemether-lumefantrine (Coartem®) orally as a 6 dose regimen for three consecutive days. Tablets are available as a fixed dose combination of 20mg artemether plus 120mg lumefantrine. The dosing will be based on the body weight and follow the manufacturer's recommendations: Body weight 5-14kg: 1 tablet; Body weight 15-24kg: 2 tablets; Body weight 25-34kg: 3 tablets; Body weight \> 34kg: 4 tablets; The respective amount of tablets is to be taken at hours 0, 8, 24, 36, 48 and 60 with fatty food.

Coartem

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients older than 1 year
• Presence of uncomplicated malaria infection confirmed by: fever or history of fever in the previous 3 days, and positive microscopy of P. malariae, P. ovale or mixed infection with parasite density \> 10 - 200000/µl of blood
• Residence in vicinity and no travel plans for the next 6 months
• Written informed consent by the patient or the legal representative and where possible, patient assent will be sought. If the patient/parent/guardian is unable to write, witnessed consent is permitted according to local ethical considerations.

You may not qualify if:

• Presence of P. falciparum monoinfection
• Presence of severe malaria (clinical WHO criteria)
• Presence of other febrile conditions
• Known history of hypersensitivity, allergic or adverse reactions to artemether or lumefantrine
• Intake of any antimalarials or antibiotics with known antimalarial activity in the past 72 hours
• Intake of an 8-aminoquinoline antimalarial or atovaquone-proguanil in preceding 28 days
• Pregnant women in first trimenon

Sponsors & Collaborators

• Albert Schweitzer Hospital: lead
• Medical University of Vienna: collaborator

Study Sites (2)

Centre de Recherches Médicales de Lambaréné, Hôpital Albert Schweitzer

Lambaréné, Moyen-Ogooué Province, 118, Gabon

Location

Centre de Recherches Médicales de Ngounié

Fougamou, Ngouni Province, 113, Gabon

Location

Related Publications (6)

• Planche T, Krishna S, Kombila M, Engel K, Faucher JF, Ngou-Milama E, Kremsner PG. Comparison of methods for the rapid laboratory assessment of children with malaria. Am J Trop Med Hyg. 2001 Nov;65(5):599-602. doi: 10.4269/ajtmh.2001.65.599.

  PMID: 11716121 BACKGROUND

• Richter J, Franken G, Mehlhorn H, Labisch A, Haussinger D. What is the evidence for the existence of Plasmodium ovale hypnozoites? Parasitol Res. 2010 Nov;107(6):1285-90. doi: 10.1007/s00436-010-2071-z. Epub 2010 Oct 5.

  PMID: 20922429 BACKGROUND

• Maguire JD, Sumawinata IW, Masbar S, Laksana B, Prodjodipuro P, Susanti I, Sismadi P, Mahmud N, Bangs MJ, Baird JK. Chloroquine-resistant Plasmodium malariae in south Sumatra, Indonesia. Lancet. 2002 Jul 6;360(9326):58-60. doi: 10.1016/S0140-6736(02)09336-4.

  PMID: 12114045 BACKGROUND

• Greenwood BM, Bradley AK, Greenwood AM, Byass P, Jammeh K, Marsh K, Tulloch S, Oldfield FS, Hayes R. Mortality and morbidity from malaria among children in a rural area of The Gambia, West Africa. Trans R Soc Trop Med Hyg. 1987;81(3):478-86. doi: 10.1016/0035-9203(87)90170-2.

  PMID: 3318021 BACKGROUND

• Perandin F, Manca N, Calderaro A, Piccolo G, Galati L, Ricci L, Medici MC, Arcangeletti MC, Snounou G, Dettori G, Chezzi C. Development of a real-time PCR assay for detection of Plasmodium falciparum, Plasmodium vivax, and Plasmodium ovale for routine clinical diagnosis. J Clin Microbiol. 2004 Mar;42(3):1214-9. doi: 10.1128/JCM.42.3.1214-1219.2004.

  PMID: 15004078 BACKGROUND

• Groger M, Veletzky L, Lalremruata A, Cattaneo C, Mischlinger J, Zoleko-Manego R, Endamne L, Klicpera A, Kim J, Nguyen T, Flohr L, Remppis J, Matsiegui PB, Adegnika AA, Agnandji ST, Kremsner PG, Mordmuller B, Mombo-Ngoma G, Ramharter M. Prospective Clinical Trial Assessing Species-Specific Efficacy of Artemether-Lumefantrine for the Treatment of Plasmodium malariae, Plasmodium ovale, and Mixed Plasmodium Malaria in Gabon. Antimicrob Agents Chemother. 2018 Feb 23;62(3):e01758-17. doi: 10.1128/AAC.01758-17. Print 2018 Mar.

  PMID: 29311086 DERIVED

MeSH Terms

Conditions

Malaria; Recurrence

Interventions

Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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

• Michael Ramharter, Prof.

  Centre de Recherches Médicales de Lambaréné

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assoc. Prof., MD, MSc

Study Record Dates

• First Submitted: April 28, 2015
• First Posted: August 19, 2015
• Study Start: October 1, 2014
• Primary Completion: October 1, 2016
• Study Completion: October 1, 2016
• Last Updated: January 25, 2017

Record last verified: 2017-01

Locations

GA (2)