AzTrials
AzTrials

MalariaPhase 3DMANCT01054248

Randomised Trial of 3 Artemisinin Combination Therapy for Malaria in Pregnancy

A Phase 3 study testing dihydroartemisinin-piperaquine, Artesunate-mefloquine and arthemeter-lumefantrin in people with Malaria, run by University of Oxford at 1 site in Thailand.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 45 years
Conditions the study is for
Malaria
What is being tested?
dihydroartemisinin-piperaquine, Artesunate-mefloquine and arthemeter-lumefantrin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
511 participants
Where
1 siteThailand
Study dates
16 Feb 2010to Sep 2016
Phase
Phase 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 45 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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
Show all 11Show fewer
  • 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

Who cannot join

  • 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
Show all 10Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Thailand1 site

  • Shoklo Malaria Research Unit

    Mae Sot, Changwat Tak

Other trials in Thailand

About this study

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

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.

Read the 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.

Conditions
Malaria
Being tested
dihydroartemisinin-piperaquine, Artesunate-mefloquine, arthemeter-lumefantrin
Keywords
pregnancy, malaria, artemisinin, vivax, falciparum
Medical subject headings
Malaria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • dihydroartemisinin-piperaquineDrug

    Also called Artekin

    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

  • Artesunate-mefloquineDrug

    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.

  • arthemeter-lumefantrinDrug

    Also called Coartem

    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).

Study groups in NCT01054248
Study groupRoleWhat they receive
MAS3ExperimentalStandard 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.
Receives: Drug: Artesunate-mefloquine
ALN+Active comparatorAugmented 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)
Receives: Drug: arthemeter-lumefantrin
DPExperimentalStandard 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
Receives: Drug: dihydroartemisinin-piperaquine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Cure rate defined as clearance of asexual parasites without recurrence within the period between treatment and delivery or a 63 day period

    Measured: Day 63 or until delivery, whichever occurs later

Secondary outcomes (9)

  1. Number of adverse events

    Measured: Day 63

  2. Biochemical and haematological changes

    Measured: Day 28

  3. Kinetic parameters of artesunate, mefloquine, piperaquine and lumefantrine

    Measured: Day 42

  4. Anaemia

    Measured: Day 63

  5. Gametocyte carriage

    Measured: Day 63

  6. Changes in the Reticulocyte counts

    Measured: Day 63

  7. Malaria infection rate at delivery and placental parasitaemia

    Measured: Delivery

  8. Pregnancy outcomes (abortions, low birth weight, premature birth, congenital abnormality, stillbirths, neonatal and infant mortality)

    Measured: Delivery

  9. Infant growth and development at 1 year of life

    Measured: 1 year after delivery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jan 2010 (estimated)
  2. Study start16 Feb 2010
  3. Primary completionSep 2016
  4. Study completionSep 2016

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Participant
Enrolment
511 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01054248
Sponsor's protocol ID
SMRU0905
Acronym
DMA
Status last verified
Mar 2022
First submitted
21 Jan 2010
Last updated
25 Mar 2022
Results posted
No
Data monitoring committee
Yes

Publications

  • Saito M, Wilaisrisak P, Pimanpanarak M, Viladpai-Nguen J, Paw MK, Koesukwiwat U, Tarning J, White NJ, Nosten F, McGready R. Comparison of lumefantrine, mefloquine, and piperaquine concentrations between capillary plasma and venous plasma samples in pregnant women with uncomplicated falciparum and vivax malaria. Antimicrob Agents Chemother. 2024 May 2;68(5):e0009324. doi: 10.1128/aac.00093-24. Epub 2024 Apr 10.

    PubMed 38597636

  • Saito M, Carrara VI, Gilder ME, Min AM, Tun NW, Pimanpanarak M, Viladpai-Nguen J, Paw MK, Haohankhunnatham W, Konghahong K, Phyo AP, Chu C, Turner C, Lee SJ, Duanguppama J, Imwong M, Bancone G, Proux S, Singhasivanon P, White NJ, Nosten F, McGready R. A randomized controlled trial of dihydroartemisinin-piperaquine, artesunate-mefloquine and extended artemether-lumefantrine treatments for malaria in pregnancy on the Thailand-Myanmar border. BMC Med. 2021 Jun 10;19(1):132. doi: 10.1186/s12916-021-02002-8.

    PubMed 34107963

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing dihydroartemisinin-piperaquine, Artesunate-mefloquine and arthemeter-lumefantrin in people with Malaria, run by University of Oxford at 1 site in Thailand.

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 11 inclusion and 10 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 25 Mar 2022. 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 Thailand. 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 phase mean?

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?

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). 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 NCT01054248, 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 25 Mar 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in