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

NCT00380146 | Completed DMC

• 1 other identifier: SEACAT2.2
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

Conditions

Malaria

Keywords

Malaria; Intermittent presumptive treatment; IPT; Pharmacokinetic; Efficacy; Gametocyte; Molecular markers

Outcome Measures

Primary Outcomes (1)

• 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

  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 Outcomes (5)

• Correlation of treatment outcome and gametocyte carriage with pharmacokinetic parameters and pregnancy status

  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

• Correlation of frequency of DHFR mutations at codons 436, 437, 540 and 581 in maternal and placental samples with treatment outcomes

  Day 42 (or day of withdrawal)

• 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

  Day of birth outcome

• Risk of harm by describing all adverse events and their causality assessments and changes in full blood count, glucose, bilirubin, creatinine, urea and ALT

  Days 3, 7, 14, 21, 28 and every 2 weeks thereafter until birth (for a minimum of 42 days) or withdrawal visit

• Capacity building by describing the training and development of study teams and their subsequent skills attained

  Duration of trial

Study Arms (1)

SP plus artesunate

EXPERIMENTAL

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

Drug: sulfadoxine-pyrimethamine

Interventions

sulfadoxine-pyrimethamine DRUG

SP plus artesunate

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Professor Karen I Barnes: lead
• Global Fund: collaborator
• Medical Research Council, South Africa: collaborator

Study Sites (1)

Ndlavela Health Centre

Ndlavela, Maputo, Mozambique

Location

MeSH Terms

Conditions

Malaria

Interventions

fanasil, pyrimethamine drug combination

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Karen I Barnes, MBChB

  University of Cape Town

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Clinical Pharmacology

Study Record Dates

• First Submitted: September 22, 2006
• First Posted: September 25, 2006
• Study Start: September 1, 2006
• Primary Completion: February 1, 2008
• Study Completion: March 1, 2008
• Last Updated: October 26, 2016

Record last verified: 2016-10

Locations

MO (1)