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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
University of Oxford
Heidelberg University
Information provided by (Responsible Party):
KEMRI-Wellcome Trust Collaborative Research Program
ClinicalTrials.gov Identifier:
NCT01190371
First received: August 24, 2010
Last updated: July 21, 2014
Last verified: July 2014
  Purpose

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


Condition Intervention Phase
Malaria
Drug: Artesunate
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Confirmation of Artemisinin Tolerance in Malaria Parasites Trial in Kilifi

Resource links provided by NLM:


Further study details as provided by KEMRI-Wellcome Trust Collaborative Research Program:

Primary Outcome Measures:
  • The primary endpoint of this study will be the re-infection-adjusted day 28 failure rate [ Time Frame: Day 0-28 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • The proportion of patients with positive malaria smears [ Time Frame: 24hr, 48hr, 72hr ] [ Designated as safety issue: No ]
    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.

  • The percentage reduction of parasitaemia from baseline [ Time Frame: 24hr, 48hr, 72hr ] [ Designated as safety issue: No ]
    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.

  • The mean time to parasite clearance [ Time Frame: Up to day 7 ] [ Designated as safety issue: No ]
    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.

  • The mean time to fever clearance [ Time Frame: Up to day 7 ] [ Designated as safety issue: No ]
    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.

  • To estimate the rates for late clinical and parasitological failure rates [ Time Frame: Days 28 and 42 ] [ Designated as safety issue: No ]
    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


Enrollment: 175
Study Start Date: April 2011
Estimated Study Completion Date: August 2014
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Artesunate
Confirmation of artemisinin tolerance
Drug: Artesunate
Oral, once daily, 7-day regimen of artesunate 2mg/kg/day
Other Name: Artesunate

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   6 Months to 10 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01190371

Locations
Kenya
Kadzinuni Dispensary
Kadzinuni, Kilifi, Kenya
Pingilikani Dispensary
Kilifi, Kenya
Junju Dispensary
Kilifi, Kenya
Sponsors and Collaborators
KEMRI-Wellcome Trust Collaborative Research Program
University of Oxford
Heidelberg University
Investigators
Principal Investigator: Roma Chilengi KEMRI Centre for Geographic Medicine Research (Coast), University of Oxford, England
Principal Investigator: Steffen Borrmann KEMRI Centre for Geographic Medicine Research (Coast), Heidelberg University of Medicine, Germany
  More Information

No publications provided

Responsible Party: KEMRI-Wellcome Trust Collaborative Research Program
ClinicalTrials.gov Identifier: NCT01190371     History of Changes
Other Study ID Numbers: KEMRI_CT_2010/0013, SSC 1821
Study First Received: August 24, 2010
Last Updated: July 21, 2014
Health Authority: Kenya: Pharmacy and Poisons Board

Keywords provided by KEMRI-Wellcome Trust Collaborative Research Program:
Artemisinin tolerance

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases
Artemisinins
Artesunate
Artemisinine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Amebicides

ClinicalTrials.gov processed this record on August 28, 2014