Effect of Liver and Blood-stage Treatment on Subsequent Plasmodium Reinfection and Morbidity

NCT02143934 | Completed Phase 4

• 1 other identifier: 07200734
• Study Type: interventional
• Target: 524
• Locations: 1 country
• Sites: 1

Brief Summary

This study specifically seeks to quantify the contribution of relapes to the burden of P. vivax infections and disease by determining on the effect of radical pre-erythrocytic and erythrocytic clearance on subsequent rates of Plasmodium spp. infection and disease in children aged 5-10 years in a treatment to re-infection study design. In order the clear liver-stage/blood-stages G6PD-normal children were randomised to receive Chloroquine (3 days, standard dose) and Coartem (3 days, standard dose) plus either i) primaquine (20 days, 0.5mg/kg) or ii) placebo (20days). These drugs were administered over a period of 4 weeks. In addition to this epidemiological data, the study will assess the natural acquisition of cellular and humoral immune responses to P. falciparum and P. vivax, thus assisting in the determination of correlates of clinical immunity to P. falciparum and P. vivax in PNG children aged 5-10 years. These data will not only be essential for development of future vaccines against P. vivax and P falciparum but provide invaluable insight into the contribution of long-lasting liver-stages to the force of infection with P. vivax that will contribute towards designing more rational approaches to the treatment of P. vivax both in the context of case management and future attempts at elimination.

Conditions

Plasmodium Vivax Infection; Plasmodium Vivax Clinical Episode; Plasmodium Falciparum Infection; Plasmodium Falciparum Clinical Episode

Keywords

Plasmodium vivax; Hypnozoites; Primaquine; Liver-stage; Blood-stage; Plasmodium falciparum

Outcome Measures

Primary Outcomes (2)

• Time to first or only Plasmodium vivax infection by light microscopy and PCR

  8 months post-baseline

• Time to first or only clinical P. vivax episode

  8 months post-baseline

Secondary Outcomes (3)

• Time to first or only P. falciparum infection by light microscopy and PCR

  8 months post-baseline

• Time to first or only P. ovale infection by light microscopy and PCR

  8 months post-baseline

• Time to first or only P. malariae infection by light microscopy and PCR

  8 months post-baseline

Study Arms (2)

Primaquine

ACTIVE COMPARATOR

Primaquine, 0.5mg/kg/day, 20 days directly observed treatment Chloroquine, 25mg/kg total dose, divided over 3 days directly observed treatment Artemether-Lumefantrine, 3 days BD

Drug: Primaquine; Drug: Chloroquine; Drug: Artemether Lumefantrine

Placebo

PLACEBO COMPARATOR

Placebo, 20 days directly observed treatment Chloroquine, mg/kg, 3 days directly observed treatment Artemether-Lumefantrine, 3 days BD

Drug: Placebo; Drug: Chloroquine; Drug: Artemether Lumefantrine

Interventions

Primaquine DRUG

Primaquine

Placebo DRUG

Sugar pills, appearance identical to Primaquine tablets

Placebo

Chloroquine DRUG

Placebo; Primaquine

Artemether Lumefantrine DRUG

Also known as: Coartem

Placebo; Primaquine

Eligibility Criteria

• Age: 5 Years - 10 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• aged 5-10 years (±3 months)
• permanent residents of the area
• absence of history of hypersensitivity reactions to the drugs

You may not qualify if:

• chronic illness
• severe malnutrition (weight-for-age nutritional Z score \[WAZ\] \<60th percentile)
• severe anemia (Hb \<5 g/dL),
• G-6-PD deficiency (\<60% G-6-PD activity)
• permanent disability, which prevents or impedes study participation. Any 1 or more of the criteria is sufficient to exclude study participation.

Sponsors & Collaborators

• Papua New Guinea Institute of Medical Research: lead
• Walter and Eliza Hall Institute of Medical Research: collaborator
• Swiss Tropical & Public Health Institute: collaborator
• Barcelona Centre for International Health Research: collaborator

Study Sites (1)

PNG Institute of Medical Research

Maprik, East Sepik Province, Papua New Guinea

Location

Related Publications (7)

• Potter GE, Callier V, Shrestha B, Joshi S, Dwivedi A, Silva JC, Laurens MB, Follmann DA, Deye GA. Can incorporating genotyping data into efficacy estimators improve efficiency of early phase malaria vaccine trials? Malar J. 2023 Dec 19;22(1):383. doi: 10.1186/s12936-023-04802-0.

  PMID: 38115002 DERIVED

• Potter GE, Callier V, Shrestha B, Joshi S, Dwivedi A, Silva JC, Laurens MB, Follmann DA, Deye GA. Can incorporating genotyping data into efficacy estimators improve efficiency of early phase malaria vaccine trials? Res Sq [Preprint]. 2023 Sep 22:rs.3.rs-3370731. doi: 10.21203/rs.3.rs-3370731/v1.

  PMID: 37790581 DERIVED

• Stadler E, Cromer D, Mehra S, Adekunle AI, Flegg JA, Anstey NM, Watson JA, Chu CS, Mueller I, Robinson LJ, Schlub TE, Davenport MP, Khoury DS. Population heterogeneity in Plasmodium vivax relapse risk. PLoS Negl Trop Dis. 2022 Dec 19;16(12):e0010990. doi: 10.1371/journal.pntd.0010990. eCollection 2022 Dec.

  PMID: 36534705 DERIVED

• Holzschuh A, Gruenberg M, Hofmann NE, Wampfler R, Kiniboro B, Robinson LJ, Mueller I, Felger I, White MT. Co-infection of the four major Plasmodium species: Effects on densities and gametocyte carriage. PLoS Negl Trop Dis. 2022 Sep 13;16(9):e0010760. doi: 10.1371/journal.pntd.0010760. eCollection 2022 Sep.

  PMID: 36099312 DERIVED

• Hofmann NE, Karl S, Wampfler R, Kiniboro B, Teliki A, Iga J, Waltmann A, Betuela I, Felger I, Robinson LJ, Mueller I. The complex relationship of exposure to new Plasmodium infections and incidence of clinical malaria in Papua New Guinea. Elife. 2017 Sep 1;6:e23708. doi: 10.7554/eLife.23708.

  PMID: 28862132 DERIVED

• Wampfler R, Hofmann NE, Karl S, Betuela I, Kinboro B, Lorry L, Silkey M, Robinson LJ, Mueller I, Felger I. Effects of liver-stage clearance by Primaquine on gametocyte carriage of Plasmodium vivax and P. falciparum. PLoS Negl Trop Dis. 2017 Jul 21;11(7):e0005753. doi: 10.1371/journal.pntd.0005753. eCollection 2017 Jul.

  PMID: 28732068 DERIVED

• Robinson LJ, Wampfler R, Betuela I, Karl S, White MT, Li Wai Suen CS, Hofmann NE, Kinboro B, Waltmann A, Brewster J, Lorry L, Tarongka N, Samol L, Silkey M, Bassat Q, Siba PM, Schofield L, Felger I, Mueller I. Strategies for understanding and reducing the Plasmodium vivax and Plasmodium ovale hypnozoite reservoir in Papua New Guinean children: a randomised placebo-controlled trial and mathematical model. PLoS Med. 2015 Oct 27;12(10):e1001891. doi: 10.1371/journal.pmed.1001891. eCollection 2015 Oct.

  PMID: 26505753 DERIVED

MeSH Terms

Conditions

Malaria, Vivax; Malaria, Falciparum

Interventions

Primaquine; Chloroquine; Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

• Ivo Mueller, PhD

  Walter and Eliza Hall Institute of Medical Research; Centre de Recerca en Salut Internacional de Barcelona (CRESIB)

  PRINCIPAL INVESTIGATOR

• Inoni Betuela, MD PhD

  PNG Institute of Medical Research

  PRINCIPAL INVESTIGATOR

• Louis Schofield, PhD

  Walter and Eliza Hall Institute of Medical Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2014
• First Posted: May 21, 2014
• Study Start: August 1, 2009
• Primary Completion: May 1, 2010
• Study Completion: May 1, 2014
• Last Updated: May 21, 2014

Record last verified: 2014-05

Locations

PA (1)