Anti-Malarial Drug Resistance in Cameroon

January 11, 2017 updated by: Brian Greenwood, London School of Hygiene and Tropical Medicine

Anti-malarial Drug Resistance in Cameroon: Therapeutic Efficacy and Biological Markers of Resistance

The project is a three-armed study designed to evaluate the efficacy of amodiaquine(AQ), sulphadoxine-pyrimethamine(SP) and(AQ+SP) in three sites in Cameroon that differ in their baseline characteristics for malaria. In addition, drug resistance will be determined by measurement of blood drug levels,and identification of molecular markers of resistance.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The objectives of this study are:- .

  • to evaluate the therapeutic efficacy of amodiaquine(AQ), Fansidar(SP) and the combination amodiaquine/Fansidar in three sites in Cameroon namely, Garoua (Sahel-savanna), Yaounde (Forest-savannah mosaic) and Limbe (Littoral-forest)
  • to determine the prevalence of molecular markers associated with resistance to chloroquine,AQ,and SP in Limbe and Garoua and of mefloquine in Yaounde.
  • to investigate biological factors that may enhance anti-malaria therapeutic efficacy. This will involve an exploratory, pilot study conducted during the second year of the program.

Patients will be rapidly screened for temperature and sent to the laboratory to determine the presence or absence of malaria parasites. The patients will then be examined clinically for inclusion or exclusion. Consent will be sort from the parents and the children randomised and assigned study numbers. To avoid bias in assigning the patients to groups and to ensure equal numbers in the treatment groups, blocked randomization will be performed, using a table of random variables of varying block sizes. The physician is blinded to what treatment the patient gets.

Amodiaquine will be administered at 10mg/kg on each of the three days to children in the AQ treatment group, together with Fansidar dummy tablets. Fansidar will be given at 25 mg/kg on day 0 and quinine as rescue drug at 10mg/kg per 8H for 6 days. For the AQ/SP combination, on D0, patients will be given both 25 mg/kg SP and 10mg/kg AQ. On subsequent days the AQ or its dummy tablets(SP arm) will be given.

Clinical assessment during the study will include: physical examination and monitoring of vital signs on D0, D3, D7, D14 and D28. Hematological measurements will include: blood films, haemoglobin,glucose,blood drug levels,and baseline haematology. A maximum of 3ml of blood will be withdrawn from the patients in Yaoundé for complete analyses(see below). For patients recruited at Limbe and Garoua only finger prick blood filter paper samples will be obtained.

Day 0 blood samples (3mL) will be collected aseptically by venepuncture before therapy from each of 50 patients in Yaoundé using acid-citrate-dextrose buffer (ACD) as anticoagulant. This will be processed to provide plasma for immunological determinations and for haematology and blood drug level determinations.

The molecular characterization of diversity and mutations:

  • the genetic heterogeneity of the study population will be established using primers for msp1 and msp2 shown previously to distinguish between strains.
  • PCR products will be digested with restriction enzyme (RFLP-PCR) for pyrimethamine resistance genes dhfr and dhps, and for chloroquine resistant strains of the pfcrtgene.

Study Type

Interventional

Enrollment

755

Phase

  • Phase 2
  • Phase 3

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 4 years (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  • Children 6-59 months of age
  • Recorded temperature between 37.5oC and 39.5 oC
  • Signs/symptoms of acute uncomplicated P. falciparum malaria.
  • Positive microscopy for mono-infection with P falciparum malaria
  • Asexual blood stage parasitaemia in the range 1,000 to 100,000 asexual parasites per ul
  • Consent from parent or guardian of a child.
  • No other apparent cause for the child's illness.

Exclusion criteria:

  • Presence of signs of severe complicated falciparum malaria.
  • Cerebral malaria (unrousable coma)
  • Vomiting > twice within preceding 24 hours
  • More than one convulsion within preceding 24 hours
  • Inability to drink or breast-feed, or to take oral medication
  • Haemoglobin less than 5g/dl or a hematocrit of less than 15%.
  • Documented evidence of adequate treatment with drugs expected to be effective in the preceding 72 hours
  • Presence of underlying diseases (cardiac, renal, hepatic,malnutrition, gastrointestinal)
  • History of allergy to study drug
  • Inability to attend for the stipulated follow-up visits,
  • Difficulty in accessing the health facility, or any situation or condition which may compromise the patients ability to comply with the trial procedures.

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: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Adequate clinical and parasitological response(ACPR) on Day 28

Secondary Outcome Measures

Outcome Measure
ACPR Day 14
Early treatment failure, between days 1 and 3
Late treatment failure, between days 4 and 14

Collaborators and Investigators

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

Sponsor

London School of Hygiene and Tropical Medicine

Collaborators

University of Yaounde

Investigators

  • Principal Investigator: Wilfred Mbacham, ScD, Laboratory for Public Health Biotechnology, University of Yaounde I

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

August 1, 2003

Study Completion

May 1, 2005

Study Registration Dates

First Submitted

September 5, 2005

First Submitted That Met QC Criteria

September 5, 2005

First Posted (ESTIMATE)

September 7, 2005

Study Record Updates

Last Update Posted (ESTIMATE)

January 12, 2017

Last Update Submitted That Met QC Criteria

January 11, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ITDCVG34

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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