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Have Malaria Infections in Kenya Become Less Responsive to Artemisinin Treatment? (CATMAP)

22. februar 2018 oppdatert av: KEMRI-Wellcome Trust Collaborative Research Program

Confirmation of Artemisinin Tolerance in Malaria Parasites Trial in Kilifi

The purpose of this study is to determine whether P. falciparum infections in Kilifi District have developed tolerance to the artemisinin class of drugs.

Studieoversikt

Status

Ukjent

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

Artemisinin-based combination therapies (ACT) are the treatment of choice for episodes of uncomplicated P. falciparum malaria in all endemic countries. Rapid clearance of pathogenic blood stage malaria parasites by artemisinins is associated with swift recovery from mild malaria and reduced mortality from severe forms of the disease. In Kenya, and most malaria endemic sub-saharan Africa, artemether-lumefantrine has been introduced as first-line treatment in the public health care sector in 2006. Alarmingly, despite the short time since the introduction of ACTs artemisinin-resistant P. falciparum malaria has already emerged in South-East Asia, an area that has historically been the cradle of global spreads of drug-resistant malaria parasites.

In a previous study in Kilifi we have observed a significant drop in early response rates to treatment with two ACTs from 2005 to 2008. Conventional markers of potential changes in anti-parasitic host immunity, drug exposure, or baseline parasite biomass could not account for the observed time-dependent change in response rates.

This protocol aims to establish with reasonable confidence whether P. falciparum infections in Kilifi District have developed tolerance to the artemisinin class of drugs. We propose to study treatment response rates to an established 7-day regimen of artesunate alone in the treatment of uncomplicated P. falciparum malaria in children aged 6 months to 10 years, at the KEMRI study site in Pingilikani, Kilifi District, Kenya. The study will also assess (i) pharmacokinetic parameters of artesunate; (ii) ex vivo and in vitro chemosensitivity of parasite isolates to DHA; (iii) genetic determinants of altered in vivo and in vitro responses to DHA; and (iv) ex vivo expression profiles in normally vs. slowly responding P. falciparum infections before and during treatment.

Studietype

Intervensjonell

Registrering (Faktiske)

175

Fase

  • Fase 4

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Kenya
      • Kilifi, Kenya
        • Junju Dispensary
      • Kilifi, Kenya
        • Pingilikani Dispensary
    • Kilifi
      • Kadzinuni, Kilifi, Kenya
        • Kadzinuni Dispensary

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

6 måneder til 10 år (Barn)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria:

  • aged between 6 months to 10 years, inclusive
  • mono-infection with P. falciparum detected by microscopy;
  • parasitaemia of 10,000-300,000/µl asexual forms;
  • presence of axillary temperature ≥ 37.5 °C or history of fever during the past 24 h;
  • ability to swallow oral medication;
  • ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule; and
  • informed consent from a parent or guardian.

Exclusion Criteria:

  • presence of clinical danger signs: not able to drink or breast-feed, vomiting (>twice in 24 hours), recent history of convulsions (>1 in 24h), unconscious state, unable to sit or stand;
  • mixed or mono-infection with another Plasmodium species detected by microscopy;
  • presence of severe acute malnutrition defined as weight for height <70% of the median NCHS/WHO (Appendix 2);
  • presence of febrile conditions due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhoea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases, HIV/AIDS);
  • regular medication, which may interfere with antimalarial pharmacokinetics or pharmacodynamic assessments (e.g., antibiotics with known antimalarial activity); and
  • history of hypersensitivity reactions or contraindications to any of the medicine(s) being tested or used as alternative treatment(s).

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Annen: Artesunate
Confirmation of artemisinin tolerance
Legemiddel: Artesunate
Oral, once daily, 7-day regimen of artesunate 2mg/kg/day

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
The primary endpoint of this study will be the re-infection-adjusted day 28 failure rate
Tidsramme: Day 0-28
Cure is defined as clearance of asexual P. falciparum parasitemia until day 7 and no recrudescence of asexual P. falciparum parasitemia until day 28. Re-infections are defined by genetic fingerprinting methods as newly emerging parasite clones during follow-up.
Day 0-28

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
The proportion of patients with positive malaria smears
Tidsramme: 24hr, 48hr, 72hr
The number of patients still having parasites at these time points divided by the total treated will give an estimate of early cure rates or estimates of early treatment failure rates as a percentage.
24hr, 48hr, 72hr
The percentage reduction of parasitaemia from baseline
Tidsramme: 24hr, 48hr, 72hr
These results will be used to compute the percentage of uncleared parasites so as to evaluate cases of early treatment failure according to the WHO criteria.
24hr, 48hr, 72hr
The mean time to parasite clearance
Tidsramme: Up to day 7
Estimated by parametric survival analysis will give an estimate of how long the drug takes to clear parasites from the time of first dosing till the time of the first negative smear.
Up to day 7
The mean time to fever clearance
Tidsramme: Up to day 7
Estimated by parametric survival analysis mean time to fever clearance will be estimated to reflect the time it takes the the temperature to settle down consistently for at least 24 hours.
Up to day 7
To estimate the rates for late clinical and parasitological failure rates
Tidsramme: Days 28 and 42
We will estimate the cumulative incidence of success and failure rates at days 28 and 42, by both PCR-uncorrected and PCR-corrected for recrudescence
Days 28 and 42

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

KEMRI-Wellcome Trust Collaborative Research Program

Samarbeidspartnere

University of Oxford
Heidelberg University

Etterforskere

  • Hovedetterforsker: Roma Chilengi, KEMRI Centre for Geographic Medicine Research (Coast), University of Oxford, England
  • Hovedetterforsker: Steffen Borrmann, KEMRI Centre for Geographic Medicine Research (Coast), Heidelberg University of Medicine, Germany

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. april 2011

Primær fullføring (Faktiske)

1. november 2011

Studiet fullført (Forventet)

1. desember 2018

Datoer for studieregistrering

Først innsendt

24. august 2010

Først innsendt som oppfylte QC-kriteriene

26. august 2010

Først lagt ut (Anslag)

27. august 2010

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

23. februar 2018

Siste oppdatering sendt inn som oppfylte QC-kriteriene

22. februar 2018

Sist bekreftet

1. juli 2017

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • KEMRI_CT_2010/0013
  • SSC 1821 (Annen identifikator: KEMRI Scientific Steering Committee)

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Nei

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

produkt produsert i og eksportert fra USA

Nei

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