MalariaPhase 2/3NCT01082718
Pharmacokinetics of Mefloquine-Artesunate in Pregnant Women With Uncomplicated Plasmodium Falciparum Infection
A Phase 2/3 study testing Mefloquine Artesunate in people with Malaria and Pregnancy, run by Centers for Disease Control and Prevention.
Trial summary
Artemisinin-based combination therapies (ACTs) are now the treatment of choice for malaria in non-pregnant individuals living in areas with established chloroquine resistance; they have been shown to be both safe and highly efficacious. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- 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
- 0 participants
- Where
- No sites listed yet
- Study dates
- Mar 2010to Oct 2010
- 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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Cases: Pregnant women, age ≥18 years, in 2nd or 3rd trimester (gestational age ≥12 weeks determined by LMP and confirmed by fundal height measurement) Controls: Non-pregnant women ≥18 years old (negative urine pregnancy test)
- Presence of P. falciparum ≤ 50,000 parasites/microliter
- Fever (≥37.5C) or history of fever in preceding 48 hours
- Willing to sign or thumb print informed consent
- Willing to be hospitalized for 3 days and to return for scheduled follow up visits for treatment and observation until delivery
- Willing to deliver in health facility
Who cannot join
- Pregnancy < 12 weeks
- Presence of malaria species other than P. falciparum on the slide (P. vivax, P. malariae, or P. ovale, or mixed infection (P. falciparum in combination with any other malaria species)
- History of allergy or hypersensitivity to interventional drugs
- Exposure to antimalarial drugs and other drugs with antimalarial activity within the past 2 months, as determined by history from the woman.
- Patients taking drugs with possible interaction with study drugs (ie, digoxin or warfarin)
- History or family history of epilepsy or psychiatric disorder
Show all 12Show fewer
- 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, but not the follow-up for drug efficacy.
- History of chronic disease including diabetes, renal failure, hepatic failure, heart disease requiring anti-arrhythmic drugs or warfarin, AIDS (HIV itself will not be an exclusion, but anyone with AIDS or HIV requiring HAART will be excluded), hemoglobinopathy,
- Participant's inability to return for follow up visits
- Age <18 years
- Hb<8g/dl
About this study
Artemisinin-based combination therapies (ACTs) are now the treatment of choice for malaria in non-pregnant individuals living in areas with established chloroquine resistance; they have been shown to be both safe and highly efficacious. There is rapidly increasing experience with artemisinin derivatives in the 2nd and 3rd trimesters of pregnancy, with over 1,000 well documented cases with no reported serious adverse effects to mother or fetus (WHO Malaria Treatment Guidelines, 2006). Many countries in Latin America have abandoned the previous 1st line regimen of Quinine-Clindamycin for treatment of malaria in pregnancy, a complex and poorly tolerated regimen with low adherence, in favor of ACTs, despite limited safety and pharmacokinetic data on the use of these compounds in pregnant women. Lack of pharmacokinetic data may lead to underdosing of pregnant women, with subsequent reduced efficacy and increased potential for development of resistance.
One ACT regimen, Artesunate-Mefloquine, has been developed as a fixed-dose combination (Farmanguinhos Artesunato + Mefloquina), as part of an international collaborative research effort led by Drugs for Neglected Diseases Initiative (DNDi), and manufactured by Farmanguinhos, laboratory of the Brazilian Ministry of Health. Initial clinical trials suggest that it is very well tolerated and efficacious in both pregnant and non-pregnant individuals. The convenient dosing afforded by a fixed drug combination make this a very promising candidate for treatment of pregnant women with malaria. Preliminary pharmacokinetic data from mefloquine monotherapy and prophylaxis suggest that the peak concentration of mefloquine is lowered in pregnant women. Prior to wide-spread adoption of the Artesunate-Mefloquine combination, further studies on safety, efficacy, and dose optimization are imperative. We propose to compare the pharmacokinetics of the fixed combination of mefloquine-artesunate (MA) for treatment of P.falciparum in 28 pregnant women in the second and third trimesters to the pharmacokinetics of this regimen in 28 matched non-pregnant P.falciparum infected women. This will allow us to determine whether the standard adult dose is sufficient for pregnant women.
- Being tested
- Mefloquine Artesunate
- Keywords
- Malaria, Pregnancy, Pharmacokinetics, Brazil
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mefloquine ArtesunateDrug
Also called Artesunato- mefloquina
Mefloquine-artesunate fixed dose combination (Farmanguinhos): Artesuanto 100 mg and Mefloquine 220mg per tablet, dosed once daily for 3 days such that mefloquine dose is approximately 8mg/kg/day.
| Study group | Role | What they receive |
|---|---|---|
| Pregnant women | Experimental | Pregnant women with P. falciparum malaria Receives: Drug: Mefloquine Artesunate |
| Non pregnant women | Active comparator | Non pregnant women with P. falciparum malaria Receives: Drug: Mefloquine Artesunate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the curve of Mefloquine - artesunate in pregnant versus matched non-pregnant women with P. falciparum malaria
Measured: Multiple measures up to 63 days
Secondary outcomes (1)
PCR correct cure rate on Day 63
Measured: Day 63
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2010 (estimated)
- Study startMar 2010
- Primary completionOct 2010 (estimated)
- Study completionOct 2010 (estimated)
Why it stopped: Logistical difficulties
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 2/3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centers for Disease Control and Prevention
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Meghna Desai, MPH PhD, Principal investigator, Centers for Disease Control and Prevention
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01082718
- Sponsor's protocol ID
- PAACT PK
- Status last verified
- Apr 2012
- First submitted
- 8 Mar 2010
- Last updated
- 13 Apr 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics of Mefloquine-Artesunate in Pregnant Women With Uncomplicated Plasmodium Falciparum Infection
- ClinicalTrials.gov ID
- NCT01082718
- Acronym / sponsor ID
- PAACT PK
- Keywords
- Malaria, Pregnancy, Pharmacokinetics, Brazil
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Logistical difficulties
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Centers for Disease Control and PreventionUS federal agency
- Study start
- Mar 2010
- Primary completion
- Oct 2010 (estimated)
- Study completion
- Oct 2010 (estimated)
- First posted
- 9 Mar 2010 (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.
Artemisinin-based combination therapies (ACTs) are now the treatment of choice for malaria in non-pregnant individuals living in areas with established chloroquine resistance; they have been shown to be both safe and highly efficacious. There is rapidly increasing experience with artemisinin derivatives in the 2nd and 3rd trimesters of pregnancy, with over 1,000 well documented cases with no reported serious adverse effects to mother or fetus (WHO Malaria Treatment Guidelines, 2006). Many countries in Latin America have abandoned the previous 1st line regimen of Quinine-Clindamycin for treatment of malaria in pregnancy, a complex and poorly tolerated regimen with low adherence, in favor of ACTs, despite limited safety and pharmacokinetic data on the use of these compounds in pregnant women. Lack of pharmacokinetic data may lead to underdosing of pregnant women, with subsequent reduced efficacy and increased potential for development of resistance.
One ACT regimen, Artesunate-Mefloquine, has been developed as a fixed-dose combination (Farmanguinhos Artesunato + Mefloquina), as part of an international collaborative research effort led by Drugs for Neglected Diseases Initiative (DNDi), and manufactured by Farmanguinhos, laboratory of the Brazilian Ministry of Health. Initial clinical trials suggest that it is very well tolerated and efficacious in both pregnant and non-pregnant individuals. The convenient dosing afforded by a fixed drug combination make this a very promising candidate for treatment of pregnant women with malaria. Preliminary pharmacokinetic data from mefloquine monotherapy and prophylaxis suggest that the peak concentration of mefloquine is lowered in pregnant women. Prior to wide-spread adoption of the Artesunate-Mefloquine combination, further studies on safety, efficacy, and dose optimization are imperative. We propose to compare the pharmacokinetics of the fixed combination of mefloquine-artesunate (MA) for treatment of P.falciparum in 28 pregnant women in the second and third trimesters to the pharmacokinetics of this regimen in 28 matched non-pregnant P.falciparum infected women. This will allow us to determine whether the standard adult dose is sufficient for pregnant women.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pregnant women | Experimental | Drug: Mefloquine ArtesunatePregnant women with P. falciparum malaria |
| Non pregnant women | Active comparator | Drug: Mefloquine ArtesunateNon pregnant women with P. falciparum malaria |
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)
- Cases: Pregnant women, age ≥18 years, in 2nd or 3rd trimester (gestational age ≥12 weeks determined by LMP and confirmed by fundal height measurement) Controls: Non-pregnant women ≥18 years old (negative urine pregnancy test)
- Presence of P. falciparum ≤ 50,000 parasites/microliter
- Fever (≥37.5C) or history of fever in preceding 48 hours
- Willing to sign or thumb print informed consent
- Willing to be hospitalized for 3 days and to return for scheduled follow up visits for treatment and observation until delivery
Key exclusion criteria (12 listed)
- Pregnancy < 12 weeks
- Presence of malaria species other than P. falciparum on the slide (P. vivax, P. malariae, or P. ovale, or mixed infection (P. falciparum in combination with any other malaria species)
- History of allergy or hypersensitivity to interventional drugs
- Exposure to antimalarial drugs and other drugs with antimalarial activity within the past 2 months, as determined by history from the woman.
- Patients taking drugs with possible interaction with study drugs (ie, digoxin or warfarin)
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: Artesunato- mefloquinaMefloquine-artesunate fixed dose combination (Farmanguinhos): Artesuanto 100 mg and Mefloquine 220mg per tablet, dosed once daily for 3 days such that mefloquine dose is approximately 8mg/kg/day. | Drug | Non pregnant women, Pregnant women |
Primary outcome
Area under the curve of Mefloquine - artesunate in pregnant versus matched non-pregnant women with P. falciparum malaria
Time frame: Multiple measures up to 63 days
1 secondary outcome
PCR correct cure rate on Day 63
Time frame: Day 63
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2012.
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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.
Meghna Desai, MPH PhD principal investigator
Centers for Disease Control and Prevention
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Mefloquine Artesunate in people with Malaria and Pregnancy, run by Centers for Disease Control and Prevention.
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 12 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: withdrawn, as of the sponsor's last update on 13 Apr 2012. Status can change between updates, so confirm with the study contact before making plans.
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 was withdrawn before enrolling participants, so there are no results.
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?
Area under the curve of Mefloquine - artesunate in pregnant versus matched non-pregnant women with P. falciparum malaria (time frame: Multiple measures up to 63 days). 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 13 Apr 2012.