Parasite Clearance Time and Time to Recurrent Infection Following Treatment With Artemether/Lumefantrine (PCT)

March 15, 2014 updated by: Richard Mwaiswelo, Muhimbili University of Health and Allied Sciences

Parasite Clearance Time and Time to Recurrent Infection Following Treatment With Artemether/Lumefantrine Among Children With Uncomplicated P. Falciparum Malaria Five Years After Wide Scale Use of the Drug in Tanzania

Plasmodium falciparum resistance against artemisinins has been confirmed in South-East Asia and it is expressed phenotypically as a slow rate of parasite clearance. Nonetheless, it is not known whether the problem exist in Tanzania. This study assessed parasite clearance time and time to recurrent infection following treatment with Artemether/Lumefantrine (AL) among children with uncomplicated malaria.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Artemether/Lumefantrine (AL) has been in wide scale use in Tanzania since 2007 as first line treatment for uncomplicated falciparum malaria. Nonetheless, reports of confirmed resistance against Artemisinin derivatives expressed phenotypically as prolonged parasite clearance have emerged from South-East Asia (SEA), signifying reduced parasites susceptibility to the otherwise rapidly acting artemisinins. Prolonged clearance is associated with an increase in day 28 treatment failure, gametocytes carriage and transmission of resistance. Nonetheless, no detailed study has been done in East Africa to assess parasite clearance time following treatment with Artemisinin based combination therapies (ACTs).

In order to evaluate time to parasite clearance following treatment with AL, we conducted a detailed clinical trial with twenty blood sampling time points prior, during and after treatment. Detailed sampling allowed us to assess parasite clearance, and selection of Plasmodium falciparum multidrug resistance (Pfmdr) 1 N86Y and Plasmodium falciparum chloroquine resistance transporter (Pfcrt) K76T genes between different time points and its association with parasite clearance and recurrence. Furthermore, as a sensitive tool and an ideal early warning system, nested polymerase chain reaction (PCR) was used to assess parasite clearance and compare it with microscopic findings.

Study Type

Interventional

Enrollment (Actual)

45

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Tanzania
      • Dar es Salaam, Tanzania, 65001
        • Muhimbili University of Health and Allied Sciences

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months to 10 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age 6-120 months
  • Presence of asexual P. falciparum parasitaemia of 2000-200 000/μL
  • No general danger signs or severe malaria present
  • Hemoglobin ≥5 g/dL
  • History of fever within 24 hours or axillary temperature ≥ 37.5 degree Celsius
  • No other cause of fever is detectable
  • No severe malnutrition
  • Guardian/patient has consented

Exclusion Criteria:

  • general danger signs or signs of severe falciparum malaria
  • severe malnutrition
  • febrile condition due to diseases other than malaria
  • regular medication which might interfere with antimalarial pharmacokinetics
  • contraindications to any medicine being used

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Artemether/lumefantrine

Artemether/lumefantrine tablets, 6 doses, for 3 days

Dosage:

  1. tablet for body weight between 5-14.9 Kilograms.
  2. tablets for body weight between 15-24.9 Kilograms.
  3. tablets for body weight between 25-34.9 Kilograms.
Drug: Artemether/lumefantrine
Medication was given at 0, 8, 24, 36, 48 and 60 hours. Food was given to all patients prior to medication to ensure proper absorption of the drug.
Other Names:
  • Coartem

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to parasite clearance
Time Frame: 72 hours
Time to parasite clearance was assessed by taking blood samples and examining it by light microscopy prior (0 hour) and during treatment at 4, 8, 12 hours and then 6 hourly until two consecutive negative blood slides.
72 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to recurrent infection
Time Frame: 42 days
Time taken for parasites to reappear in the peripheral blood of the participant after initial treatment was assessed during the 42 days of follow up from blood samples taken on days 14, 21, 28 and 42.
42 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to parasite clearance
Time Frame: 7 days
Blood samples collect on filter papers prior (0 Hour), during and after medication at 4, 8, 12 and after every 6 hours until 72 hours and on day 7 were analyzed by PCR to assess parasite clearance. Parasite positivity after day 7 was considered as recurrent infection.
7 days
Time to alleles clearance
Time Frame: 168 hours
Time to clearance of parasites carrying Pfmdr 1 N86Y and Pfcrt K76T alleles was assessed by molecular genotyping using blood samples collected during the early phase of treatment.
168 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Muhimbili University of Health and Allied Sciences

Collaborators

Karolinska Institutet

Investigators

  • Study Director: Andreas Martensson, PhD, Karolinska Institutet

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2012

Primary Completion (Actual)

June 1, 2012

Study Completion (Actual)

July 1, 2012

Study Registration Dates

First Submitted

November 15, 2013

First Submitted That Met QC Criteria

November 23, 2013

First Posted (Estimate)

November 28, 2013

Study Record Updates

Last Update Posted (Estimate)

March 18, 2014

Last Update Submitted That Met QC Criteria

March 15, 2014

Last Verified

March 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2.0.2011

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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