- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01054248
Randomised Trial of 3 Artemisinin Combination Therapy for Malaria in Pregnancy (DMA)
A Randomised Open Label Trial Comparing Standard Dose of Dihydroartemisinin-piperaquine, Standard Fixed Artesunate-mefloquine Regimen and a Longer Regimen of Artemether-lumefantrine in the Treatment of Uncomplicated Malaria in Pregnancy
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The 3 treatment regimens are 3 days of DHA-piperaquine (DP), 3 days of artesunate-mefloquine (MAS3) with mefloquine given as 8,8,8 mg/kg per day and an augmented dose of 4 days (5 tabs BID) of artemether- lumefantrine (ALN+). This will focus on efficacy and safety. Patients will be randomized equally to one of three treatment groups.
Within the trial there are two nested pharmacokinetic studies comprising dense data on 15 women for mefloquine and artesunate and sparse data for mefloquine, lumefantrine and piperaquine. Pregnant women will be followed up until delivery or day 63 if later than delivery and their infants will be followed until the end of the first year of life The follow up of babies will be monthly until 1 year (summarized in the table). Visits will include body weight, length, head circumference, arm circumference, physical examination, motor milestones by observation and caregiver interview, developmental examination and monthly haematocrit and stool testing. The mother is free to bring her infant at any time to the clinic and investigations appropriate to the presenting complaint and symptoms will be carried out as necessary to provide care for the infant.
Infants born to mothers who have a positive peripheral smear at delivery are at risk of congenital malaria and will be actively screened weekly for 2 months. In the last study one congenital malaria P.falciparum occurred at day 21 and the infant was very sick and was cured with artesunate. Infants who are positive for malaria would have a PCR spot to verify if the malaria was congenital.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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-
Tak
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Mae Sot, Tak, Thailand
- Shoklo Malaria Research Unit
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age 18-45 years
- Viable pregnancy of any gestation as assessed by ultrasound scanning
- Microscopically confirmed uncomplicated malaria (parasitaemia ≥ 5/500 WBC) with Plasmodium falciparum or Mixed infection (i.e. P.falciparum & P.vivax/ovale/malariae) or Plasmodium vivax/ovale/malariae
- Willingness and ability to comply with the study protocol for the duration of the trial
- Written informed consent provided
- No signs of labour
Additional criteria for patients in the detailed pharmacokinetic study group (N=24 in the MAS3 arm):
- HCT>25% (based on field reading i.e. capillary sample)
- P.falciparum monoinfection
- Agree to stay in the clinic for 7 days
- Written consent to participate the detailed PK subgroup
Exclusion Criteria:
- Known hypersensitivity to the study drugs
- P.falciparum asexual stage parasitaemia ≥ 4% RBCs
- Clinical or laboratory features of severe malaria based on WHO criteria-Appendix 1
- Gastrointestinal dysfunction that could alter absorption or motility
- History or known liver diseases or other chronic diseases (excluding thalassemia & G6PD deficiency)
- Presence of intercurrent illness or any condition which in the judgement of the investigator would place the patient at undue risk or interfere with the results of the study
- Splenectomy
- Hematocrit (HCT) <20% (based on field reading i.e. capillary sample) [ *NB: Dense mefloquine pharmacokinetic exclusion if HCT < 25%]
- Taking contraindicated medications
- History of narcotic or alcohol abuse
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: MAS3
Standard three day regimen of artesunate-mefloquine (12/24 mg/kg) given as artesunate 4mg/kg/day and mefloquine 8mg/kg/day on Days 0, 1 and 2.
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Standard three day regimen of artesunate-mefloquine (12/24 mg/kg) given as artesunate 4mg/kg/day and mefloquine 8mg/kg/day on Days 0, 1 and 2.
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Active Comparator: ALN+
Augmented 4 day regimen of artemether lumefantrine 2 doses per day for 4 days.
Each dose consists of 5 tablets (20/120 mg of artemether/lumefantrine per tablet)
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Augmented 4 day regimen of artemether lumefantrine 2 doses per day for 4 days.
Each dose consists of 5 tablets (20/120 mg of artemether/lumefantrine per tablet).
Other Names:
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Experimental: DP
Standard 3 days regimen DHA-piperaquine: (DHA/PPQ 40 mg/320 mg) 2.4 mg/kg DHA and 20 mg/kg PPQ once daily for 3 days
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Standard 3 days regimen DHA-piperaquine: (DHA/PPQ 40 mg/320 mg) 2.4 mg/kg DHA and 20 mg/kg PPQ once daily for 3 days
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Cure rate defined as clearance of asexual parasites without recurrence within the period between treatment and delivery or a 63 day period
Time Frame: Day 63 or until delivery, whichever occurs later
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Day 63 or until delivery, whichever occurs later
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Number of adverse events
Time Frame: Day 63
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Day 63
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Biochemical and haematological changes
Time Frame: Day 28
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Day 28
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Kinetic parameters of artesunate, mefloquine, piperaquine and lumefantrine
Time Frame: Day 42
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Day 42
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Anaemia
Time Frame: Day 63
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Day 63
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Gametocyte carriage
Time Frame: Day 63
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Day 63
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Changes in the Reticulocyte counts
Time Frame: Day 63
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Day 63
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Malaria infection rate at delivery and placental parasitaemia
Time Frame: Delivery
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Delivery
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Pregnancy outcomes (abortions, low birth weight, premature birth, congenital abnormality, stillbirths, neonatal and infant mortality)
Time Frame: Delivery
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Delivery
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Infant growth and development at 1 year of life
Time Frame: 1 year after delivery
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1 year after delivery
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Rose McGready, MBBS, Shoklo Malaria Research Unit
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- SMRU0905
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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