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Randomised Trial of 3 Artemisinin Combination Therapy for Malaria in Pregnancy (DMA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by University of Oxford
Sponsor:
Information provided by (Responsible Party):
University of Oxford
ClinicalTrials.gov Identifier:
NCT01054248
First received: January 21, 2010
Last updated: August 27, 2013
Last verified: August 2013
History of Changes
  Purpose

This is a randomised, open label trial, comparing standard dose of dihydroartemisinin-piperaquine (DP) with standard fixed artesunate-mefloquine regimen (MAS3) and with a longer regimen of artemether-lumefantrine (ALN+) in the treatment of uncomplicated malaria in pregnant women. The sample size is 335 women in each arm which would be 1005 women in total. Pregnant patients in 2nd and 3rd trimester with acute uncomplicated malaria who meet eligibility criteria will be asked to participate in the study. The primary objective is to determine if the efficacy of DP and MAS3 are superior to ALN+ in the treatment of uncomplicated malaria in pregnancy. The study will also incorporate a dense pharmacokinetic study of mefloquine and artesunate (15 women in the MAS3 arm) and a population pharmacokinetic study for mefloquine, piperaquine and lumefantrine.


Condition Intervention Phase
Malaria
 Drug: dihydroartemisinin-piperaquine
Drug: Artesunate-mefloquine
Drug: arthemeter-lumefantrin
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:

MedlinePlus related topics: Malaria
U.S. FDA Resources

Further study details as provided by University of Oxford:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of adverse events [ Time Frame: Day 63 ] [ Designated as safety issue: Yes ]
  • Biochemical and haematological changes [ Time Frame: Day 28 ] [ Designated as safety issue: Yes ]
  • Kinetic parameters of artesunate, mefloquine, piperaquine and lumefantrine [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
  • Anaemia [ Time Frame: Day 63 ] [ Designated as safety issue: No ]
  • Gametocyte carriage [ Time Frame: Day 63 ] [ Designated as safety issue: No ]
  • Changes in the Reticulocyte counts [ Time Frame: Day 63 ] [ Designated as safety issue: No ]
  • Malaria infection rate at delivery and placental parasitaemia [ Time Frame: Delivery ] [ Designated as safety issue: No ]
  • Pregnancy outcomes (abortions, low birth weight, premature birth, congenital abnormality, stillbirths, neonatal and infant mortality) [ Time Frame: Delivery ] [ Designated as safety issue: No ]
  • Infant growth and development at 1 year of life [ Time Frame: 1 year after delivery ] [ Designated as safety issue: No ]
Estimated Enrollment: 1005
Study Start Date: February 2010
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
 Drug: Artesunate-mefloquine
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.
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)
 Drug: arthemeter-lumefantrin
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 Name: Coartem
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
 Drug: dihydroartemisinin-piperaquine
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 Name: Artekin

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.

  Eligibility
Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01054248

Contacts
Contact: Francois Nosten, MD francois@tropmedres.ac
Contact: Phaik Yeong Cheah, PhD phaikyeong@tropmedres.ac

Locations
Thailand
Shoklo Malaria Research Unit Recruiting
Mae Sot, Tak, Thailand
Contact: Rose McGready, MBBS       rose@tropmedres.ac   
Sponsors and Collaborators
University of Oxford
Investigators
Principal Investigator: Rose McGready, MBBS Shoklo Malaria Research Unit
  More Information

No publications provided

Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT01054248     History of Changes
Other Study ID Numbers: SMRU0905
Study First Received: January 21, 2010
Last Updated: August 27, 2013
Health Authority: Thailand: Ethical Committee

Keywords provided by University of Oxford:
pregnancy, malaria, artemisinin, vivax, falciparum

Additional relevant MeSH terms:
Malaria
Parasitic Diseases
Protozoan Infections
Artemether-lumefantrine combination
Artesunate
Dihydroartemisinin
Lumefantrine
Mefloquine
 Piperaquine
Amebicides
Anti-Infective Agents
Antimalarials
Antiparasitic Agents
Antiprotozoal Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on March 03, 2015