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Pharmacokinetics, Efficacy, Gametocyte Carriage, Birth Outcomes Following Sulfadoxine-pyrimethamine Intermittent Presumptive Treatment in Pregnant Women

Primary Purpose

Malaria

Status
Completed
Phase
Not Applicable
Locations
Mozambique
Study Type
Interventional
Intervention
sulfadoxine-pyrimethamine
Sponsored by
Professor Karen I Barnes
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Malaria focused on measuring Malaria, Intermittent presumptive treatment, IPT, Pharmacokinetic, Efficacy, Gametocyte, Molecular markers

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Pregnant female, older than 18 years, > 35kg.
  • Gestational age > 16 weeks (fundal height > 16cm) and below 36 weeks gestation.
  • Documented informed consent.
  • Lives close enough to the study site for reliable follow up and is willing to attend ANC and follow-up visits regularly.

Exclusion Criteria:

  • Diagnoses of uncomplicated acute P. falciparum malaria parasitaemia
  • Has received anti-malarial treatment in the past 7 days and/or sulfadoxine-pyrimethamine in the past 28 days.
  • Known hepatic or renal impairment
  • Has received chloramphenicol, cotrimoxazole or tetracyclines (including doxycycline) in the past 7 days or is likely to require these during the study period.
  • History of G6PD deficiency.
  • Has a history of allergy to any of the study drugs (including other sulphonamides e.g. cotrimoxazole).
  • Serious underlying disease that in the opinion of the clinic team and/or Principal Investigator would make the patient unsuitable for the study in terms of their safety or study analysis.
  • Imminent delivery expected.
  • Prior inclusion in this study.

Sites / Locations

  • Ndlavela Health Centre

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

SP plus artesunate

Arm Description

SP (Fansidar®, Roche South Africa) at a dose of 25/1.25mg/kg of sulfadoxine/pyrimethamine respectively on day 0 only, and artesunate (Arsumax®, Sanofi-Aventis, South Africa) at a dose of 4mg/kg on days 0, 1, and 2

Outcomes

Primary Outcome Measures

Pharmacokinetic parameters by measurement of whole blood levels of sulfadoxine and pyrimethamine and plasma levels of artesunate to determine Cmax, Tmax, AUC, half life, volume of distribution and clearance

Secondary Outcome Measures

Correlation of treatment outcome and gametocyte carriage with pharmacokinetic parameters and pregnancy status
Correlation of frequency of DHFR mutations at codons 436, 437, 540 and 581 in maternal and placental samples with treatment outcomes
Birth outcomes in terms of major congenital abnormalities, spontaneous abortions, still births and neonatal deaths, gestational age and birth weight, placental weight, newborn head circumference, arm circumference and neurological development
Risk of harm by describing all adverse events and their causality assessments and changes in full blood count, glucose, bilirubin, creatinine, urea and ALT
Capacity building by describing the training and development of study teams and their subsequent skills attained

Full Information

First Posted
September 22, 2006
Last Updated
October 25, 2016
Sponsor
Professor Karen I Barnes
Collaborators
Global Fund, Medical Research Council, South Africa
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1. Study Identification

Unique Protocol Identification Number
NCT00380146
Brief Title
Pharmacokinetics, Efficacy, Gametocyte Carriage, Birth Outcomes Following Sulfadoxine-pyrimethamine Intermittent Presumptive Treatment in Pregnant Women
Official Title
An Open-label in Vivo Drug Study to Evaluate the Pharmacokinetics, Therapeutic Efficacy, Gametocyte Carriage and Birth Outcomes Following Sulfadoxine-pyrimethamine Intermittent Presumptive Treatment (SP IPT) in Pregnant Women
Study Type
Interventional

2. Study Status

Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
September 2006 (undefined)
Primary Completion Date
February 2008 (Actual)
Study Completion Date
March 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Professor Karen I Barnes
Collaborators
Global Fund, Medical Research Council, South Africa

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The main purpose of this study is to compare the drug levels of sulfadoxine-pyrimethamine found when given to pregnant women for the prevention of malaria to those found in pregnant women given the same drug with artesunate for the treatment of malaria, and also with those drug levels found in non-pregnant women in other malaria treatment studies.
Detailed Description
Pregnancy increases the risk of malaria progression and complications with up to a 10-fold increase in the malaria case fatality rate in areas of low transmission. Sulfadoxine-pyrimethamine (SP) is used widely in Africa for the systematic intermittent presumptive, or preventive, treatment (IPTp) during the second and third trimester of pregnancy and a national program of IPTp with SP has been implemented recently in Mozambique. There is evidence that the kinetics of several other antimalarial drugs are altered in pregnancy to the extent that doses are not adequate in pregnancy, however no published study has included a pharmacokinetic component to confirm that standard doses of SP are optimal in this vulnerable patient group. This study therefore creates the opportunity to study whether the pharmacokinetic properties of SP are altered by physiological changes that occur during pregnancy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria
Keywords
Malaria, Intermittent presumptive treatment, IPT, Pharmacokinetic, Efficacy, Gametocyte, Molecular markers

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SP plus artesunate
Arm Type
Experimental
Arm Description
SP (Fansidar®, Roche South Africa) at a dose of 25/1.25mg/kg of sulfadoxine/pyrimethamine respectively on day 0 only, and artesunate (Arsumax®, Sanofi-Aventis, South Africa) at a dose of 4mg/kg on days 0, 1, and 2
Intervention Type
Drug
Intervention Name(s)
sulfadoxine-pyrimethamine
Primary Outcome Measure Information:
Title
Pharmacokinetic parameters by measurement of whole blood levels of sulfadoxine and pyrimethamine and plasma levels of artesunate to determine Cmax, Tmax, AUC, half life, volume of distribution and clearance
Time Frame
0 hours (pre treatment) and repeated on day 0 or 1 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours, and days 2, 3, 7, 14, 21, 28 and 42
Secondary Outcome Measure Information:
Title
Correlation of treatment outcome and gametocyte carriage with pharmacokinetic parameters and pregnancy status
Time Frame
0 hours (pre treatment) and repeated on day 0 or 1 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours, and days 2, 3, 7, 14, 21, 28 and 42 , and time of birth outcome
Title
Correlation of frequency of DHFR mutations at codons 436, 437, 540 and 581 in maternal and placental samples with treatment outcomes
Time Frame
Day 42 (or day of withdrawal)
Title
Birth outcomes in terms of major congenital abnormalities, spontaneous abortions, still births and neonatal deaths, gestational age and birth weight, placental weight, newborn head circumference, arm circumference and neurological development
Time Frame
Day of birth outcome
Title
Risk of harm by describing all adverse events and their causality assessments and changes in full blood count, glucose, bilirubin, creatinine, urea and ALT
Time Frame
Days 3, 7, 14, 21, 28 and every 2 weeks thereafter until birth (for a minimum of 42 days) or withdrawal visit
Title
Capacity building by describing the training and development of study teams and their subsequent skills attained
Time Frame
Duration of trial

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Pregnant female, older than 18 years, > 35kg. Gestational age > 16 weeks (fundal height > 16cm) and below 36 weeks gestation. Documented informed consent. Lives close enough to the study site for reliable follow up and is willing to attend ANC and follow-up visits regularly. Exclusion Criteria: Diagnoses of uncomplicated acute P. falciparum malaria parasitaemia Has received anti-malarial treatment in the past 7 days and/or sulfadoxine-pyrimethamine in the past 28 days. Known hepatic or renal impairment Has received chloramphenicol, cotrimoxazole or tetracyclines (including doxycycline) in the past 7 days or is likely to require these during the study period. History of G6PD deficiency. Has a history of allergy to any of the study drugs (including other sulphonamides e.g. cotrimoxazole). Serious underlying disease that in the opinion of the clinic team and/or Principal Investigator would make the patient unsuitable for the study in terms of their safety or study analysis. Imminent delivery expected. Prior inclusion in this study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Karen I Barnes, MBChB
Organizational Affiliation
University of Cape Town
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ndlavela Health Centre
City
Ndlavela
State/Province
Maputo
Country
Mozambique

12. IPD Sharing Statement

Learn more about this trial

Pharmacokinetics, Efficacy, Gametocyte Carriage, Birth Outcomes Following Sulfadoxine-pyrimethamine Intermittent Presumptive Treatment in Pregnant Women

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