Plasmodium Falciparum MalariaPhase 2/3NCT00701961
Pharmacokinetic of Mefloquine-Artesunate in Plasmodium Falciparum Malaria Infection in Pregnancy
A Phase 2/3 study testing Mefloquine-artesunate in people with Plasmodium Falciparum Malaria, run by Institute of Tropical Medicine, Belgium at 1 site in Burkina Faso.
Trial summary
Malaria in pregnancy is a major public health problem in Sub-Saharan Africa. Over the past decades, P. falciparum has shown increasing resistance to chloroquine and Sulphadoxine-Pyrimethamine, which has prompted a change in treatment approach; artemisinin containing combination therapies (ACTs) are now the standard… Read more about this study
- Who is it for?
- Ages 18 to 49 years, women only
- Conditions the study is for
- Plasmodium Falciparum Malaria
- What is being tested?
- Mefloquine-artesunate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteBurkina Faso
- Study dates
- Oct 2008to Jul 2009
- Phase
- Phase 2/3
- 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 to 49 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Plasmodium falciparum monoinfection (any density)
- At least 18 years old;
- Haemoglobin at leats 7 g/dL;
- Residence within the health facility catchment's area;
- Willing to adhere to the study requirements
- Willing to deliver in health facility
- Ability to provide written informed consent
- EITHER pregnant women in the 2nd or 3rd trimester (cases)or non-pregnant women between the ages of 18 and 49 years (controls).
Who cannot join
- Pregnancy 1st trimester
- History of known pregnancy complications or bad obstetric history such as repeated stillbirths or eclampsia;
- Known major illnesses likely to influence pregnancy outcome including diabetes mellitus, severe renal or heart disease, or active tuberculosis;
- Current cotrimoxazole prophylaxis or ARV treatment;
- Any significant presenting illness that requires hospitalization, including severe malaria;
- Intent to move out of the study catchment area before delivery or deliver at relative's home out of the catchment area.
Show all 14Show fewer
- Prior enrollment in the study or concurrent enrollment in another study.
- Unable to take oral medication
- Clear evidence of treatment with antimicrobials with antimalarial activity (erythromycin or other macrolides, co-trimoxazole or other sulfonamides, any tetracycline including doxycycline, quinolones and clindamycin) or exposure to antimalarial drugs within the week prior enrollment.
- History of allergy or hypersensivity to interventional drugs
- Patients taking drugs with possible interaction with study drugs (i.e. digoxin or warfarin)
- History or family history of epilepsy or psychiatric disorder
- Presence of signs and symptoms of severe malaria
- Inability to tolerate oral medication (repeated vomiting, impairment of consciousness). Vomiting of any of the treatment doses will lead to exclusion from the pharmacokinetic sampling.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Pharmacokinetic of the Fixed-dose Combination of Mefloquine-Artesunate in Plasmodium Falciparum Malaria Infection in Pregnant Women
Malaria in pregnancy is a major public health problem in Sub-Saharan Africa. Over the past decades, P. falciparum has shown increasing resistance to chloroquine and Sulphadoxine-Pyrimethamine, which has prompted a change in treatment approach; artemisinin containing combination therapies (ACTs) are now the standard treatment of P. falciparum malaria in areas with established resistance to traditional therapies. However, a standard approach for using ACT in pregnancy does not exist in Africa, where some countries keep on using quinine, while others allow the use of ACTs. Thus, there is need of establishing the safety and efficacy of ACTs in malaria-infected pregnant women. Since the pharmacokinetic of antimalarials may be altered during pregnancy and since available pharmacokinetic data are still somewhat limited, we propose to carry out a study confirming or disproving existing pharmacokinetic data (collected in South-East Asia), before starting any larger African efficacy and safety trials. The fixed-dose combination mefloquine-artesunate (MQ-AS), developed by the Drugs for Neglected Diseases Initiative, will be used in the study, which will compare the pharmacokinetics of MQ-AS for treatment of P.falciparum in 24 pregnant women in the second and third trimesters, to the pharmacokinetics of this regimen in 24 matched non-pregnant P.falciparum infected women. The study will be carried out in Burkina Faso.
Read the detailed description
Malaria during pregnancy constitutes a major public health problem in Sub-Saharan Africa, where it increases the risk of low birth weight (<2500g), infant mortality, infant morbidity during the first year of life, prematurity and infant anemia. Over the past decades, P. falciparum has shown increasing resistance to standard antimalarial therapy (chloroquine CQ and Sulphadoxine-Pyrimethamine). The inexorable development and spread of P. falciparum resistance to antimalarials has prompted a change in treatment approach; artemisinin containing combination therapies (ACTs) are now the standard treatment of P. falciparum malaria in areas with established resistance to the traditional therapies. The use of combinations reduces the theoretical likelihood of selecting resistant mutants; it is hoped that this strategy will delay the development of new resistances.
A standard approach for using ACT in pregnancy does not exist in Africa. Even if the World Health Organization endorses the use of ACTs for treatment of uncomplicated malaria in 2nd and 3rd trimesters of pregnancy, some countries keep on using quinine, while others allow the use of ACTs. These different approaches point out to the necessity of establishing the safety and efficacy of ACTs in malaria-infected pregnant women. Nevertheless, considering that the pharmacokinetic of antimalarials may be altered during pregnancy (potentially leading to under-dosing) and that the available safety and pharmacokinetic data are still somewhat limited, it is important to carry out a preliminary pharmacokinetic study confirming or disproving available data (collected in South-East Asia), before starting any larger African efficacy and safety trials.
The ACT regimen mefloquine-artesunate (MQ-AS) has recently been developed as a fixed-dose combination by the Drugs for Neglected Diseases Initiative (DNDi) and has been registered in Brazil (the country of manufacture) in 2008. Artesunate is an artemisinin derivative with a rapidly increasing positive experience in pregnancy, while Mefloquine (Lariam®) has been used for many years for both prevention and treatment of malaria, and has been shown to be safe in pregnant women. The convenient dosing afforded by a fixed drug combination makes MQ-AS a very promising candidate for use in treating pregnant women in Africa, as rescue treatment alternative to quinine. Since preliminary data suggest that the peak concentration of mefloquine is lowered in pregnant women, further studies on safety, efficacy, and dose optimization are imperative, prior to wide-spread adoption of this medicine.
Therefore, we propose to compare the pharmacokinetics of the fixed combination of MQ-AS for treatment of P.falciparum in 24 pregnant women in the second and third trimesters to the pharmacokinetics of this regimen in 24 matched non-pregnant P.falciparum infected women, in an African setting. This will allow for dose optimization in pregnant women.
- Conditions
- Plasmodium Falciparum Malaria
- Being tested
- Mefloquine-artesunate
- Keywords
- Mefloquine-artesunate, Malaria, Pregnancy, Pharmacokinetics, Sub-Saharan Africa, P falciparum malaria infection in pregnancy
- Medical subject headings
- Malaria, Falciparum, Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mefloquine-artesunateDrug
Also called MQ-AS
Mefloquine-artesunate fixed dose combination comprised of 100 mg of artesunate and 220mg of mefloquine per tablet, developed by DNDi and manufactured by farmanguinhos (Brazil).
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Pregnat women receiving MQ-AS fixed dose combination comprised of 100 mg of artesunate and 220mg of mefloquine per tablet, dosed once daily such that mefloquine dose is approximately 8mg/kg/day for 3 days. Receives: Drug: Mefloquine-artesunate |
| 2 | Active comparator | Non-pregnant women receiving MQ-AS fixed dose combination comprised of 100 mg of artesunate and 220mg of mefloquine per tablet, dosed once daily such that mefloquine dose is approximately 8mg/kg/day for 3 days. Receives: Drug: Mefloquine-artesunate |
What is being measured
The primary outcome is the main question the study is designed to answer.
To estimate the pharmacokinetic of MQ-AS for treatment of P. falciparum or mixed infection in pregnant compared to non-pregnant women.
Measured: 6 months
Secondary outcomes (1)
The proportion of women in each treatment group with parasitological cure at 63 days, corrected by PCR for re-infection.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2008 (estimated)
- Study startOct 2008
- Primary completionJul 2009
- Study completionJul 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Plasmodium Falciparum 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 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institute of Tropical Medicine, Belgium
- Sponsor type
- University, hospital or other
- Collaborators
- Centre Muraz, Liverpool School of Tropical Medicine
- Investigators
- Tinto Halidou, PhD, Principal investigator, Centre MurazUmberto D'Alessandro, MD, Study chair, ITM Belgium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00701961
- Sponsor's protocol ID
- ITMP0208
- Status last verified
- Sep 2010
- First submitted
- 18 Jun 2008
- Last updated
- 14 Sep 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Birgersson S, Valea I, Tinto H, Traore-Coulibaly M, Toe LC, Hoglund RM, Van Geertruyden JP, Ward SA, D'Alessandro U, Abelo A, Tarning J. Population pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum malaria in Burkina Faso: an open label trial. Wellcome Open Res. 2019 Mar 7;4:45. doi: 10.12688/wellcomeopenres.14849.2. eCollection 2019.
PubMed 32025570Valea I, Tinto H, Traore-Coulibaly M, Toe LC, Lindegardh N, Tarning J, Van Geertruyden JP, D'Alessandro U, Davies GR, Ward SA. Pharmacokinetics of co-formulated mefloquine and artesunate in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum infection in Burkina Faso. J Antimicrob Chemother. 2014 Sep;69(9):2499-507. doi: 10.1093/jac/dku154. Epub 2014 Jun 2.
PubMed 24891429
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Pharmacokinetic of the Fixed-dose Combination of Mefloquine-Artesunate in Plasmodium Falciparum Malaria Infection in Pregnant Women
- ClinicalTrials.gov ID
- NCT00701961
- Acronym / sponsor ID
- ITMP0208
- Conditions
- Plasmodium Falciparum Malaria
- Keywords
- Mefloquine-artesunate, Malaria, Pregnancy, Pharmacokinetics, Sub-Saharan Africa, P falciparum malaria infection in pregnancy
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Institute of Tropical Medicine, BelgiumUniversity, hospital or other
- Collaborators
- Centre Muraz, Liverpool School of Tropical Medicine
- Study start
- Oct 2008
- Primary completion
- Jul 2009 (actual)
- Study completion
- Jul 2009 (actual)
- First posted
- 19 Jun 2008 (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.
Malaria in pregnancy is a major public health problem in Sub-Saharan Africa. Over the past decades, P. falciparum has shown increasing resistance to chloroquine and Sulphadoxine-Pyrimethamine, which has prompted a change in treatment approach; artemisinin containing combination therapies (ACTs) are now the standard treatment of P. falciparum malaria in areas with established resistance to traditional therapies. However, a standard approach for using ACT in pregnancy does not exist in Africa, where some countries keep on using quinine, while others allow the use of ACTs. Thus, there is need of establishing the safety and efficacy of ACTs in malaria-infected pregnant women. Since the pharmacokinetic of antimalarials may be altered during pregnancy and since available pharmacokinetic data are still somewhat limited, we propose to carry out a study confirming or disproving existing pharmacokinetic data (collected in South-East Asia), before starting any larger African efficacy and safety trials. The fixed-dose combination mefloquine-artesunate (MQ-AS), developed by the Drugs for Neglected Diseases Initiative, will be used in the study, which will compare the pharmacokinetics of MQ-AS for treatment of P.falciparum in 24 pregnant women in the second and third trimesters, to the pharmacokinetics of this regimen in 24 matched non-pregnant P.falciparum infected women. The study will be carried out in Burkina Faso.
Detailed description
Malaria during pregnancy constitutes a major public health problem in Sub-Saharan Africa, where it increases the risk of low birth weight (<2500g), infant mortality, infant morbidity during the first year of life, prematurity and infant anemia. Over the past decades, P. falciparum has shown increasing resistance to standard antimalarial therapy (chloroquine CQ and Sulphadoxine-Pyrimethamine). The inexorable development and spread of P. falciparum resistance to antimalarials has prompted a change in treatment approach; artemisinin containing combination therapies (ACTs) are now the standard treatment of P. falciparum malaria in areas with established resistance to the traditional therapies. The use of combinations reduces the theoretical likelihood of selecting resistant mutants; it is hoped that this strategy will delay the development of new resistances.
A standard approach for using ACT in pregnancy does not exist in Africa. Even if the World Health Organization endorses the use of ACTs for treatment of uncomplicated malaria in 2nd and 3rd trimesters of pregnancy, some countries keep on using quinine, while others allow the use of ACTs. These different approaches point out to the necessity of establishing the safety and efficacy of ACTs in malaria-infected pregnant women. Nevertheless, considering that the pharmacokinetic of antimalarials may be altered during pregnancy (potentially leading to under-dosing) and that the available safety and pharmacokinetic data are still somewhat limited, it is important to carry out a preliminary pharmacokinetic study confirming or disproving available data (collected in South-East Asia), before starting any larger African efficacy and safety trials.
The ACT regimen mefloquine-artesunate (MQ-AS) has recently been developed as a fixed-dose combination by the Drugs for Neglected Diseases Initiative (DNDi) and has been registered in Brazil (the country of manufacture) in 2008. Artesunate is an artemisinin derivative with a rapidly increasing positive experience in pregnancy, while Mefloquine (Lariam®) has been used for many years for both prevention and treatment of malaria, and has been shown to be safe in pregnant women. The convenient dosing afforded by a fixed drug combination makes MQ-AS a very promising candidate for use in treating pregnant women in Africa, as rescue treatment alternative to quinine. Since preliminary data suggest that the peak concentration of mefloquine is lowered in pregnant women, further studies on safety, efficacy, and dose optimization are imperative, prior to wide-spread adoption of this medicine.
Therefore, we propose to compare the pharmacokinetics of the fixed combination of MQ-AS for treatment of P.falciparum in 24 pregnant women in the second and third trimesters to the pharmacokinetics of this regimen in 24 matched non-pregnant P.falciparum infected women, in an African setting. This will allow for dose optimization in pregnant women.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Mefloquine-artesunatePregnat women receiving MQ-AS fixed dose combination comprised of 100 mg of artesunate and 220mg of mefloquine per tablet, dosed once daily such that mefloquine dose is approximately 8mg/kg/day for 3 days. |
| 2 | Active comparator | Drug: Mefloquine-artesunateNon-pregnant women receiving MQ-AS fixed dose combination comprised of 100 mg of artesunate and 220mg of mefloquine per tablet, dosed once daily such that mefloquine dose is approximately 8mg/kg/day for 3 days. |
Who may qualify
- Ages
- 18 to 49 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Plasmodium falciparum monoinfection (any density)
- At least 18 years old;
- Haemoglobin at leats 7 g/dL;
- Residence within the health facility catchment's area;
- Willing to adhere to the study requirements
Key exclusion criteria (14 listed)
- Pregnancy 1st trimester
- History of known pregnancy complications or bad obstetric history such as repeated stillbirths or eclampsia;
- Known major illnesses likely to influence pregnancy outcome including diabetes mellitus, severe renal or heart disease, or active tuberculosis;
- Current cotrimoxazole prophylaxis or ARV treatment;
- Any significant presenting illness that requires hospitalization, including severe malaria;
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 |
|---|---|---|
| Mefloquine-artesunateAlso: MQ-ASMefloquine-artesunate fixed dose combination comprised of 100 mg of artesunate and 220mg of mefloquine per tablet, developed by DNDi and manufactured by farmanguinhos (Brazil). | Drug | 1, 2 |
Primary outcome
To estimate the pharmacokinetic of MQ-AS for treatment of P. falciparum or mixed infection in pregnant compared to non-pregnant women.
Time frame: 6 months
1 secondary outcome
The proportion of women in each treatment group with parasitological cure at 63 days, corrected by PCR for re-infection.
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2010.
- Derived from this study: PubMed 32025570Birgersson S, Valea I, Tinto H, Traore-Coulibaly M, Toe LC, Hoglund RM, Van Geertruyden JP, Ward SA, D'Alessandro U, Abelo A, Tarning J. Population pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum malaria in Burkina Faso: an open label trial. Wellcome Open Res. 2019 Mar 7;4:45. doi: 10.12688/wellcomeopenres.14849.2. eCollection 2019.
- Derived from this study: PubMed 24891429Valea I, Tinto H, Traore-Coulibaly M, Toe LC, Lindegardh N, Tarning J, Van Geertruyden JP, D'Alessandro U, Davies GR, Ward SA. Pharmacokinetics of co-formulated mefloquine and artesunate in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum infection in Burkina Faso. J Antimicrob Chemother. 2014 Sep;69(9):2499-507. doi: 10.1093/jac/dku154. Epub 2014 Jun 2.
Related trials for Plasmodium Falciparum Malaria
RecruitingPhase 1
Safety, Tolerability and Efficacy of PfSPZ-LARC2 Vaccine Against CHMI in Malaria-Naïve Adults
Malaria Falciparum
Not yet recruiting
Three-arm Cluster Randomised Control Trial Evaluation of Guardian Spatial Emanator as a Complimentary Vector Control Tool in Papua New Guinea
Malaria
Active, not recruitingPhase 4
Improving Neonatal Health Through Rapid Malaria Testing in Early Pregnancy With High-Sensitivity Diagnostics
Malaria,Falciparum, Malaria in Pregnancy
Not yet recruiting
Permethrin-Treated Baby Wraps for Malaria Prevention in Refugee Settings
Malaria (Plasmodium Falciparum), Malaria Incidence
RecruitingPhase 1/2
DON in Pediatric Cerebral Malaria
Malaria, Cerebral
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.
Tinto Halidou, PhD principal investigator
Centre Muraz
Umberto D'Alessandro, MD study chair
ITM Belgium
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Mefloquine-artesunate in people with Plasmodium Falciparum Malaria, run by Institute of Tropical Medicine, Belgium at 1 site in Burkina Faso.
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 8 inclusion and 14 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: finished, as of the sponsor's last update on 14 Sep 2010. 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 Burkina Faso. 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.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To estimate the pharmacokinetic of MQ-AS for treatment of P. falciparum or mixed infection in pregnant compared to non-pregnant women. (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00701961, which also lists 2 linked publications.
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 14 Sep 2010.