- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00331708
Artesunate Plus Sulfadoxine-pyrimethamine Pharmacokinetics, Efficacy, Gametocytes Carriage and Birth Outcomes in Pregnant Women With Malaria
October 25, 2016 updated by: Professor Karen I Barnes
An Open-label in Vivo Drug Study to Evaluate Artesunate Plus Sulfadoxine-pyrimethamine (ASSP) Pharmacokinetics, Therapeutic Efficacy, Gametocyte Carriage and Birth Outcomes in Pregnant Women With Uncomplicated Falciparum Malaria
The main purpose of this study is to compare the drug levels of artesunate and sulfadoxine-pyrimethamine found in pregnant women with malaria to those drug levels found in non-pregnant women from other studies.
In addition the efficacy and safety of the study drugs will be determined for pregnant women and their babies.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Detailed Description
The resistance of Plasmodium falciparum to anti-malarial drugs is a serious impediment to the control of malaria, and this poses a particular problem for the treatment of pregnant women, a group especially vulnerable to malaria; pregnancy increases the risk of disease progression and complications with up to a 10-fold increase in the malaria case fatality rate in areas of low transmission.
As falciparum parasites can sequester in the placenta, pregnant women have been shown to develop recrudescence up to 85 days after quinine treatment, and are at increased risk of gametocyte carriage.
Artemisinin-based combination therapies have been shown to improve cure rates and to delay antimalarial resistance.
In humans the efficacy and safety of artesunate in the treatment of malaria in pregnancy has been studied in over 1000 women in which no evidence of foetal harm was demonstrated.
Quinine is the only alternative currently available in Mozambique for treating malaria in pregnancy however there is relatively little data available on its efficacy or safety.
There is no published information on the pharmacokinetics of SP in pregnancy, however data show a marked reduction in bioavailability of artesunate and its active metabolite, dihydroartemisinin.
Thus, we cannot be confident that the standard dosage regimens of SP and of artesunate are optimal for the treatment of acute uncomplicated malaria in pregnancy or whether altered pharmacokinetics is contributing to the SP-treatment failures observed in pregnancy.
This study creates the opportunity to study whether the pharmacokinetic properties of SP and artesunate are altered by physiological changes that occur during pregnancy.
Study Type
Interventional
Enrollment (Actual)
3
Phase
- Not Applicable
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
-
-
Maputo
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Ndlavela, Maputo, Mozambique
- Ndlavela Health Centre
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-
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
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Female
Description
Inclusion Criteria:
- Pregnant female, older than 18 years, > 35kg.
- Gestational age > 16 weeks (fundal height > 16cm) and below 36 weeks gestation.
- Diagnoses of uncomplicated acute P. falciparum malaria parasitaemia of up to 250 000 asexual parasites/ul blood with axillary temperature of greater than or equal to 37.5°C or history of fever (defined as fever within the previous 24 hours).
- Documented written informed consent.
- Lives close enough to the study site for reliable follow up and is willing to attend ANC and follow-up visits regularly.
- Is willing to stop taking folate for 7 days if applicable.
Exclusion Criteria:
- Has received anti-malarial treatment in the past 7 days.
- Severely ill (based on WHO Criteria for severe malaria ) or if patient is considered, in the opinion of the investigator or designee, to have moderately severe malaria (e.g. prostrate, repeated vomiting, dehydrated) or other danger signs (Appendix 2).
- Known hepatic or renal impairment
- Has received chloramphenicol 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, or other artemisinin derivatives e.g. co-artemether).
- 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
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 |
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Experimental: Artesunate plus sulphadoxine-pyrimethamine
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
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Pharmacokinetic parameters by measurement of whole blood levels of sulfadoxine and pyrimethamine and plasma levels of artesunate and its active metabolite dihydroartemisinin to determine Cmax, Tmax, AUC, half life, volume of distribution and clearance
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Correlation of treatment outcome with pharmacokinetic parameters and pregnancy status.
|
Secondary Outcome Measures
Outcome Measure |
---|
Association of gametocyte carriage with pregnancy status
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Correlation of frequency of DHFR mutations at codons 108, 51, 59 (164) and DHPS mutations at codons 436, 437, 540 and 581 in maternal and placental samples with treatment outcome
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Birth outcomes in terms of congenital abnormalities, spontaneous abortions, still births and neonatal deaths, gestational age and birth weight, placental weight, newborn head circumference
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Risk of harm by describing adverse events and their causality assessments, neurodevelopmental assessment of infants and changes in full blood count (or haemoglobin), glucose, bilirubin, creatinine, urea and ALT
|
Capacity building by describing the training and development of study teams and their subsequent skills attained.
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Karen I Barnes, MBChB, University of Cape Town
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
April 1, 2006
Primary Completion (Actual)
July 1, 2007
Study Completion (Actual)
July 1, 2007
Study Registration Dates
First Submitted
May 30, 2006
First Submitted That Met QC Criteria
May 30, 2006
First Posted (Estimate)
May 31, 2006
Study Record Updates
Last Update Posted (Estimate)
October 26, 2016
Last Update Submitted That Met QC Criteria
October 25, 2016
Last Verified
October 1, 2016
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Infections
- Vector Borne Diseases
- Parasitic Diseases
- Protozoan Infections
- Malaria
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antineoplastic Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Antimalarials
- Anthelmintics
- Folic Acid Antagonists
- Schistosomicides
- Antiplatyhelmintic Agents
- Anti-Infective Agents, Urinary
- Renal Agents
- Pyrimethamine
- Artesunate
- Sulfadoxine
- Fanasil, pyrimethamine drug combination
Other Study ID Numbers
- SEACAT2.1
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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