MalariaNCT00331708
Artesunate Plus Sulfadoxine-pyrimethamine Pharmacokinetics, Efficacy, Gametocytes Carriage and Birth Outcomes in Pregnant Women With Malaria
A study testing Artesunate plus sulfadoxine-pyrimethamine in people with Malaria, run by Professor Karen I Barnes at 1 site in Mozambique.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Malaria
- What is being tested?
- Artesunate plus sulfadoxine-pyrimethamine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteMozambique
- Study dates
- Apr 2006to Jul 2007
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Malaria
- Being tested
- Artesunate plus sulfadoxine-pyrimethamine
- Keywords
- Malaria, Efficacy, Pharmacokinetic, Gametocyte, Molecular markers, Sulfadoxine-pyrimethamine, Artesunate, Artemisinin
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Artesunate plus sulfadoxine-pyrimethamineDrug
| Study group | Role | What they receive |
|---|---|---|
| Artesunate plus sulphadoxine-pyrimethamine | Experimental | Not described Receives: Drug: Artesunate plus sulfadoxine-pyrimethamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Correlation of treatment outcome with pharmacokinetic parameters and pregnancy status.
Secondary outcomes (5)
Association of gametocyte carriage with pregnancy status
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
Birth outcomes in terms of congenital abnormalities, spontaneous abortions, still births and neonatal deaths, gestational age and birth weight, placental weight, newborn head circumference
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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2006 (estimated)
- Study startApr 2006
- Primary completionJul 2007
- Study completionJul 2007
Why it stopped: Lack of suitable participants
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MalariaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Professor Karen I Barnes
- Sponsor type
- University, hospital or other
- Collaborators
- Global Fund, Medical Research Council, South Africa
- Responsible party
- Sponsor-investigator, Professor Karen I Barnes, University of Cape Town
- Investigators
- Karen I Barnes, MBChB, Principal investigator, University of Cape Town
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00331708
- Sponsor's protocol ID
- SEACAT2.1
- Status last verified
- Oct 2016
- First submitted
- 30 May 2006
- Last updated
- 26 Oct 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00331708
- Acronym / sponsor ID
- SEACAT2.1
- Conditions
- Malaria
- Keywords
- Malaria, Efficacy, Pharmacokinetic, Gametocyte, Molecular markers, Sulfadoxine-pyrimethamine, Artesunate, Artemisinin
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of suitable participants
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Professor Karen I BarnesUniversity, hospital or other
- Collaborators
- Global Fund, Medical Research Council, South Africa
- Study start
- Apr 2006
- Primary completion
- Jul 2007 (actual)
- Study completion
- Jul 2007 (actual)
- First posted
- 31 May 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Artesunate plus sulphadoxine-pyrimethamine | Experimental | Drug: Artesunate plus sulfadoxine-pyrimethamine |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Artesunate plus sulfadoxine-pyrimethamine | Drug | Artesunate plus sulphadoxine-pyrimethamine |
Primary outcome
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
Correlation of treatment outcome with pharmacokinetic parameters and pregnancy status.
5 secondary outcomes
Association of gametocyte carriage with pregnancy status
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
Birth outcomes in terms of congenital abnormalities, spontaneous abortions, still births and neonatal deaths, gestational age and birth weight, placental weight, newborn head circumference
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.
Results and safety
The study was stopped early (reason given: Lack of suitable participants). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Karen I Barnes, MBChB principal investigator
University of Cape Town
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Artesunate plus sulfadoxine-pyrimethamine in people with Malaria, run by Professor Karen I Barnes at 1 site in Mozambique.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Mozambique. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Lack of suitable participants). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2016.