NCT01669941

Brief Summary

Malaria in pregnancy (MiP) due to Plasmodium falciparum infection is a major cause of maternal morbidity and poor birth outcomes. Intermittent preventive treatment in pregnancy (IPTp) with Sulfadoxine pyrimethamine (SP), the administration of SP at predefined intervals in the second and third trimesters of pregnancy irrespective of the presence of malaria parasitemia, is currently recommended for HIV-negative women in all areas with stable moderate to high transmission of malaria. Due to increasing resistance to SP, it is no longer used as a treatment for symptomatic malaria, and the efficacy of IPTp-SP seems to be decreased. This study aims to look at a new drug, Dihydroartemisinin-Piperaquine (DP) for IPTp, as well as to explore the strategy of intermittent screening and treatment in pregnancy (ISTp) with DP. This strategy uses increased screening at time of focused antenatal care (FANC) with treatment of women who screen positive. The hypothesis is that the efficacy of both IPTp-DP and ISTp-DP will be associated with a reduction in malaria infection at delivery among HIV(-) women when compared to IPTp-SP, in an area with decreasing malaria transmission and high levels of SP resistance in Kenya.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,546

participants targeted

Target at P75+ for phase_4 pregnancy

Timeline
Completed

Started Aug 2012

Typical duration for phase_4 pregnancy

Geographic Reach
1 country

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 2012

Completed
14 days until next milestone

First Submitted

Initial submission to the registry

August 15, 2012

Completed
6 days until next milestone

First Posted

Study publicly available on registry

August 21, 2012

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2014

Completed
1.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2015

Completed
Last Updated

March 6, 2017

Status Verified

March 1, 2017

Enrollment Period

2.2 years

First QC Date

August 15, 2012

Last Update Submit

March 3, 2017

Conditions

PregnancyMalaria

Keywords

PregnancyPlasmodiumMalariaPreventionKenyaPiperaquineDihydroartemisinin-PiperaquineSulfadoxine Pyrimethamine

Outcome Measures

Primary Outcomes (1)

  • Maternal malaria at delivery

    Active or recent infection at delivery measured as the composite of peripheral and placental malaria, detected by: positive peripheral blood smear or RDT or positive placental smear, RDT, or histopathology

    Delivery

Secondary Outcomes (5)

  • Decreased fetal morbidity

    Delivery

  • Frequency of fetal congenital malformations

    At delivery

  • Pharmacokinetics- piperaquine level

    At baseline, and day 2 and day 7 following dosing.

  • level of antibodies to variant surface antigens (VSAs)

    At delivery

  • Frequency of maternal adverse events

    At each ANC visit and at delivery

Study Arms (3)

IPTp-DP

EXPERIMENTAL

At each ANC visit, women will be given treatment with Dihydroartemisinin-piperaquine for three days, with the daily number of tablets depending on the weight of the woman; two tablets for women weighing 24- 35.9kg, three tablets for women weighing 36 to 74.9 kg, and four tablets for women weighing 75kg or more. The first dose will be observed; the woman will be given the additional 2 doses to take at home and there may be a home visit to confirm that the tablets were taken.

Drug: IPTp-DP

ISTp-DP

EXPERIMENTAL

At each ANC visit, women will be screened for malaria using a combined HRP-2/ pLDH (P. falciparum/ pan-malaria) rapid diagnostic test, and if they test positive, will be treated with dihydroartemisinin-piperaquine (DP). Each tablet will contain 40 mg dihydroartemisinin and 320 mg piperaquine. Treatment will be given for three days, with the daily number of tablets depending on the weight of the woman; two tablets for women weighing 24- 35.9kg, three tablets for women weighing 36 to 74.9 kg, and four tablets for women weighing 75kg or more. The first dose will be observed; the woman will be given the additional 2 doses to take at home

Drug: ISTp-DP

IPTp-SP

ACTIVE COMPARATOR

Treatment with a single dose of three tablets of sulfadoxine-pyrimethamine, each containing sulfadoxine (500 mg) and pyrimethamine (25 mg) at each FANC visit. This is the standard regimen.

Drug: IPTp-SP

Interventions

IPTp-SPDRUG

3 tablets of sulfadoxine (500 mg) and pyrimethamine (25 mg) given at each ANC visit

Also known as: Fansidar, SP
IPTp-SP
IPTp-DPDRUG

At each ANC visit: treatment with Dihydroartemisinin-piperaquine for three days, with the daily number of tablets depending on the weight of the woman; two tablets for women weighing 24- 35.9kg, three tablets for women weighing 36 to 74.9 kg, and four tablets for women weighing 75kg or more. The first dose will be observed; the woman will be given the additional 2 doses to take at home and there may be a home visit to confirm that the tablets were taken.

Also known as: Eurartesim, Duocotexin
IPTp-DP
ISTp-DPDRUG

At each ANC visit, women will be screened for malaria using a combined HRP-2/ pLDH (P. falciparum/ pan-malaria) rapid diagnostic test, and if positive, treated with dihydroartemisinin-piperaquine. Each tablet will contain 40 mg dihydroartemisinin and 320 mg piperaquine. Treatment will be given for three days, with the daily number of tablets depending on the weight of the woman; two tablets for women weighing 24- 35.9kg, three tablets for women weighing 36 to 74.9 kg, and four tablets for women weighing 75kg or more. The first dose will be observed; the woman will be given the additional 2 doses to take at home

Also known as: Eurartesim, Duocotexin
ISTp-DP

Eligibility Criteria

Sexfemale
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Viable pregnancy assessed by Doppler
  • Gestational age 16 to 32 weeks (inclusive) by fundal height
  • No history of IPTp use during this pregnancy
  • Willing to participate and complete the study schedule
  • Willing to sign or thumb print informed consent
  • Resident of study area and intending to stay in the area for the duration of the follow-up
  • Willing to deliver in the labor ward of the study clinic or hospital
  • HIV negative at enrolment

You may not qualify if:

  • HIV positive or unknown
  • Residence outside study area or planning to move out in the 12 months following enrolment
  • High risk pregnancy, including any pre-existing illness likely to cause complication of pregnancy (hypertension, diabetes, asthma, epilepsy, renal disease, liver disease, fistula repair, leg or spine deformity)
  • Severe anemia requiring blood transfusion (Hb ≤ 7.0 g/dL) at enrolment
  • Known allergy or previous adverse reaction to any of the study drugs
  • Unable to give informed consent (for example due to mental disability)
  • Gestational age \>32 weeks
  • Previous IPTp during the current pregnancy
  • Participating in other malaria intervention studies
  • Known or suspected cardiac disease
  • Patients taking drugs in any of the following classes: antiarrhythmic agents, neuroleptics, macrolides, and certain antimalarial drugs such as mefloquine, chloroquine, halofantrine and lumefantrine.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Bondo District Hospital

Bondo, Bondo, 40601, Kenya

Location

Lwak Mission Hospital

Rarieda, Nyanza, Kenya

Location

Siaya District Hospital

Siaya, Nyanza, 40600, Kenya

Location

Madiany sub-District Hospital

Madiany, Kenya

Location

Related Publications (2)

  • Chotsiri P, Gutman JR, Ahmed R, Poespoprodjo JR, Syafruddin D, Khairallah C, Asih PBS, L'lanziva A, Otieno K, Kariuki S, Ouma P, Were V, Katana A, Price RN, Desai M, Ter Kuile FO, Tarning J. Piperaquine Pharmacokinetics during Intermittent Preventive Treatment for Malaria in Pregnancy. Antimicrob Agents Chemother. 2021 Feb 17;65(3):e01150-20. doi: 10.1128/AAC.01150-20. Print 2021 Feb 17.

    PMID: 33361303DERIVED

  • Desai M, Gutman J, L'lanziva A, Otieno K, Juma E, Kariuki S, Ouma P, Were V, Laserson K, Katana A, Williamson J, ter Kuile FO. Intermittent screening and treatment or intermittent preventive treatment with dihydroartemisinin-piperaquine versus intermittent preventive treatment with sulfadoxine-pyrimethamine for the control of malaria during pregnancy in western Kenya: an open-label, three-group, randomised controlled superiority trial. Lancet. 2015 Dec 19;386(10012):2507-19. doi: 10.1016/S0140-6736(15)00310-4. Epub 2015 Sep 28.

    PMID: 26429700DERIVED

Related Links

MeSH Terms

Conditions

Malaria

Interventions

fanasil, pyrimethamine drug combination

Condition Hierarchy (Ancestors)

Protozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne Diseases

Study Officials

  • Meghna Desai, PhD MPH

    Centers for Disease Control and Prevention

    PRINCIPAL INVESTIGATOR

  • Abraham Katana, MD

    Kenya Medical Research Institute

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Medical Officer

Study Record Dates

First Submitted

August 15, 2012

First Posted

August 21, 2012

Study Start

August 1, 2012

Primary Completion

October 1, 2014

Study Completion

December 1, 2015

Last Updated

March 6, 2017

Record last verified: 2017-03

Locations

KE(4)