NCT03208179

Brief Summary

This study evaluates the efficacy and safety of monthly intermittent preventive treatment using dihydroartemisinin piperaquine (DP) alone or in combination with azithromycin (AZ) compared to sulphadoxine-pyrimethamine (SP) for the prevention of malaria in pregnant women in the second and third trimester.

Trial Health

90
On Track

Trial Health Score

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

Enrollment
4,680

participants targeted

Target at P75+ for phase_3 pregnancy

Timeline
Completed

Started Mar 2018

Shorter than P25 for phase_3 pregnancy

Geographic Reach
3 countries

7 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

First Submitted

Initial submission to the registry

June 30, 2017

Completed
5 days until next milestone

First Posted

Study publicly available on registry

July 5, 2017

Completed
9 months until next milestone

Study Start

First participant enrolled

March 29, 2018

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 15, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 15, 2020

Completed
Last Updated

June 27, 2022

Status Verified

June 1, 2022

Enrollment Period

2 years

First QC Date

June 30, 2017

Last Update Submit

June 22, 2022

Conditions

PregnancyMalaria in PregnancyMalaria

Keywords

Malaria in PregnancyIntermittent Preventive TreatmentIPTp

Outcome Measures

Primary Outcomes (1)

  • Adverse pregnancy outcome

    Composite of foetal loss (spontaneous abortion or stillbirth), or singleton live births born small-for-gestational age (SGA), or with low birthweight (LBW), or preterm (PT) (SGA-LBW-PT), or subsequent neonatal death by day 28.

    8 months

Secondary Outcomes (27)

  • Composite of foetal loss and neonatal mortality

    8 months

  • SGA-LBW-PT composite

    6 months

  • SGA

    6 months

  • LBW

    6 months

  • PT

    6 months

  • +22 more secondary outcomes

Study Arms (3)

IPTp-SP

ACTIVE COMPARATOR

Stat course of 3 tablets of quality-assured SP (tablets of 500 mg of sulphadoxine and 25 mg of pyrimethamine) at each scheduled antenatal visit

Drug: sulphadoxine-pyrimethamine

IPTp-DP

EXPERIMENTAL

Dihydroartemisinin-piperaquine \[3 to 5 tablets of DP (tablets of 40 mg of dihydroartemisinin and 320 mg of piperaquine, based on bodyweight) daily for 3 days\] + placebo AZ at each scheduled antenatal visit

Drug: dihydroartemisinin-piperaquine

IPTp-DPAZ

EXPERIMENTAL

Dihydroartemisinin-piperaquine \[3 to 5 tablets of DP (tablets of 40 mg of dihydroartemisinin and 320 mg of piperaquine, based on bodyweight) daily for 3 days\] + AZ tablet \[1.5g over 3 days as 500mg per day\] at each scheduled antenatal visit.

Drug: dihydroartemisinin-piperaquine plus azithromycin

Interventions

dihydroartemisinin-piperaquineDRUG

Women randomised to this intervention will receive 3 day treatment dose of dihydroartemisinin-piperaquine by body weight plus azithromycin placebo

Also known as: Eurartesim
IPTp-DP
sulphadoxine-pyrimethamineDRUG

Women randomised to this intervention will receive stat dose of 3 tablets of 500 mg sulphadoxine and 25 mg of pyrimethamine each (total dose of 1,500mg sulphadoxine and 75mg pyrimethamine) on a single day of clinic visit

Also known as: Fansidar
IPTp-SP
dihydroartemisinin-piperaquine plus azithromycinDRUG

Women randomised to this intervention will receive 3 day treatment dose of dihydroartemisinin-piperaquine by body weight plus azithromycin (500mg)

Also known as: Eurartesim plus Zithromax
IPTp-DPAZ

Eligibility Criteria

Age16 Years+
Sexfemale(Gender-based eligibility)
Gender Eligibility DetailsPregnant female
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Pregnant women between 16-28 weeks' gestation
  • Viable singleton pregnancy
  • Resident of the study area
  • Willing to adhere to scheduled and unscheduled study visit procedures
  • Willing to deliver in a study clinic or hospital
  • Provide written informed consent

You may not qualify if:

  • Multiple pregnancies (i.e. twin/triplets)
  • HIV-positive
  • Known heart ailment
  • Severe malformations or non-viable pregnancy if observed by ultrasound
  • History of receiving IPTp-SP during this current pregnancy
  • Unable to give consent
  • Known allergy or contraindication to any of the study drugs

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

Ahero Sud-countyHospital

Ahero, Kisumu County, Kenya

Location

Homa Bay County Hospital

Homa Bay, Kenya

Location

Rabour Sub-county Hospital

Kisumu, Kenya

Location

Chikwawa District Hospital

Chikwawa, Malawi

Location

Mangochi District Hospital

Mangochi, Malawi

Location

Handeni District Hospital

Handeni, Tanzania

Location

Korogwe District Hospital

Korogwe, Tanzania

Location

Related Publications (3)

  • Gore-Langton GR, Madanitsa M, Barsosio HC, Minja DTR, Mosha J, Kavishe RA, Mtove G, Gesase S, Msemo OA, Kariuki S, Otieno K, Phiri KS, Lusingu JPA, Mukerebe C, Manjurano A, Ikigo P, Saidi Q, Onyango ED, Schmiegelow C, Dodd J, Hill J, Hansson H, Alifrangis M, Gutman J, Hunter PJ, Klein N, Ashorn U, Khalil A, Cairns M, Ter Kuile FO, Chico RM. Prevalence and risk factors of curable sexually transmitted and reproductive tract infections and malaria co-infection among pregnant women at antenatal care booking in Kenya, Malawi and Tanzania: a cross-sectional study of randomised controlled trial data. BMJ Public Health. 2024 Sep 18;2(2):e000501. doi: 10.1136/bmjph-2023-000501. eCollection 2024 Dec.

    PMID: 40018559DERIVED

  • Madanitsa M, Barsosio HC, Minja DTR, Mtove G, Kavishe RA, Dodd J, Saidi Q, Onyango ED, Otieno K, Wang D, Ashorn U, Hill J, Mukerebe C, Gesase S, Msemo OA, Mwapasa V, Phiri KS, Maleta K, Klein N, Magnussen P, Lusingu JPA, Kariuki S, Mosha JF, Alifrangis M, Hansson H, Schmiegelow C, Gutman JR, Chico RM, Ter Kuile FO. Effect of monthly intermittent preventive treatment with dihydroartemisinin-piperaquine with and without azithromycin versus monthly sulfadoxine-pyrimethamine on adverse pregnancy outcomes in Africa: a double-blind randomised, partly placebo-controlled trial. Lancet. 2023 Mar 25;401(10381):1020-1036. doi: 10.1016/S0140-6736(22)02535-1. Epub 2023 Mar 10.

    PMID: 36913959DERIVED

  • Mtove G, Abdul O, Kullberg F, Gesase S, Scheike T, Andersen FM, Madanitsa M, Ter Kuile FO, Alifrangis M, Lusingu JPA, Minja DTR, Schmiegelow C. Weight change during the first week of life and a new method for retrospective prediction of birthweight among exclusively breastfed newborns. Acta Obstet Gynecol Scand. 2022 Mar;101(3):293-302. doi: 10.1111/aogs.14323. Epub 2022 Feb 13.

    PMID: 35156190DERIVED

MeSH Terms

Conditions

Malaria

Interventions

fanasil, pyrimethamine drug combinationAzithromycin

Condition Hierarchy (Ancestors)

Protozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne Diseases

Intervention Hierarchy (Ancestors)

ErythromycinMacrolidesPolyketidesLactonesOrganic Chemicals

Study Officials

  • Simon K Kariuki, PhD

    Kenya Medical Research Institute

    PRINCIPAL INVESTIGATOR

  • Frank Mosha, PhD

    Kilimanjaro Christian Medical University College

    PRINCIPAL INVESTIGATOR

  • John Lusingu, PhD

    National Institute for Medical Research

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
The study will be a partially placebo-controlled involving a single placebo for AZ. To further minimise bias, an objective primary outcome measure will be used and all staff will be masked to the treatment assignment of individual women. The trial statistician will also be masked in regard to the treatment code when he develops the statistical analysis plan and writes the statistical programmes, which will be validated and completed using dummy randomisation codes. The actual allocation will only be provided to the study team after locking of the database and approval of the statistical analysis plan by the independent Data Monitoring and Ethics Committee (DMEC) before they review any trial results. The study statistician conducting the interim analysis will remain masked throughout the analysis.
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 30, 2017

First Posted

July 5, 2017

Study Start

March 29, 2018

Primary Completion

March 15, 2020

Study Completion

March 15, 2020

Last Updated

June 27, 2022

Record last verified: 2022-06

Data Sharing

IPD Sharing
Will share

Individual, de-identified participant data will be made available for meta-analyses as soon as the data analysis is completed, with the understanding that results of the meta-analysis will not be published prior to the results of the individual trial without prior agreement of the investigators. No later than 5 years after the publication of the trial a fully de-identified data set will be available for sharing purposes

Shared Documents
STUDY PROTOCOL, ICF
Time Frame
No later than 5 years after publication
Access Criteria
Open access

Locations

TA(2)MA(2)KE(3)