Improving PRegnancy Outcomes With Intermittent preVEntive Treatment in Africa

NCT ID: NCT03208179

Last Updated: 2022-06-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

4680 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-03-29

Study Completion Date

2020-03-15

Brief Summary

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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.

Detailed Description

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Intermittent preventive treatment with sulphadoxine-pyrimethamine (IPTp-SP) is one of the pillars of malaria prevention in pregnancy in sub-Saharan Africa, in addition to prompt case management and use of long lasting insecticide treated bednets. However, mounting resistance to SP by Plasmodium falciparum increasing renders IPTP-SP ineffective.

Two exploratory trials in Uganda and Kenya demonstrated that IPTp with DP was superior to IPTp-SP for the prevention of malaria infection in pregnancy. However, neither study was adequately powered to look at adverse birth outcomes. This study is a confirmatory efficacy trial in Malawi, Tanzania and Kenya to determine the efficacy and safety of IPTp with DP alone or in combination with AZ.

This will be a 3-arm trial, superiority, partial blinded, placebo controlled, randomized trial comparing IPTp with SP, versus IPTp with DP alone, and IPTp with DP+AZ with the following hypotheses:

* IPTp with DP is superior to IPTp with SP in preventing adverse pregnancy outcomes.
* The combination of DP with AZ further reduces adverse pregnancy outcomes compared to IPTp with DP alone.

Conditions

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Pregnancy Malaria in Pregnancy Malaria

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
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.

Study Groups

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IPTp-SP

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

Group Type ACTIVE_COMPARATOR

sulphadoxine-pyrimethamine

Intervention Type DRUG

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

IPTp-DP

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

Group Type EXPERIMENTAL

dihydroartemisinin-piperaquine

Intervention Type DRUG

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

IPTp-DPAZ

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.

Group Type EXPERIMENTAL

dihydroartemisinin-piperaquine plus azithromycin

Intervention Type DRUG

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

Interventions

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dihydroartemisinin-piperaquine

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

Intervention Type DRUG

sulphadoxine-pyrimethamine

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

Intervention Type DRUG

dihydroartemisinin-piperaquine plus azithromycin

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

Intervention Type DRUG

Other Intervention Names

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Eurartesim Fansidar Eurartesim plus Zithromax

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

16 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Kamuzu University of Health Sciences

OTHER

Sponsor Role collaborator

Kenya Medical Research Institute

OTHER

Sponsor Role collaborator

Malawi-Liverpool-Wellcome Trust Clinical Research Programme

OTHER

Sponsor Role collaborator

National Institute for Medical Research, Tanzania

OTHER_GOV

Sponsor Role collaborator

Kilimanjaro Christian Medical Centre, Tanzania

OTHER

Sponsor Role collaborator

University of Copenhagen

OTHER

Sponsor Role collaborator

Centers for Disease Control and Prevention

FED

Sponsor Role collaborator

London School of Hygiene and Tropical Medicine

OTHER

Sponsor Role collaborator

University College, London

OTHER

Sponsor Role collaborator

Tampere University

OTHER

Sponsor Role collaborator

University of Bergen

OTHER

Sponsor Role collaborator

University of Massachusetts, Worcester

OTHER

Sponsor Role collaborator

University of Toronto

OTHER

Sponsor Role collaborator

University of Melbourne

OTHER

Sponsor Role collaborator

Foundation for Innovative New Diagnostics, Switzerland

OTHER

Sponsor Role collaborator

Liverpool School of Tropical Medicine

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Simon K Kariuki, PhD

Role: PRINCIPAL_INVESTIGATOR

Kenya Medical Research Institute

Frank Mosha, PhD

Role: PRINCIPAL_INVESTIGATOR

Kilimanjaro Christian Medical University College

John Lusingu, PhD

Role: PRINCIPAL_INVESTIGATOR

National Institute for Medical Research

Locations

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Ahero Sud-countyHospital

Ahero, Kisumu County, Kenya

Site Status

Homa Bay County Hospital

Homa Bay, , Kenya

Site Status

Rabour Sub-county Hospital

Kisumu, , Kenya

Site Status

Chikwawa District Hospital

Chikwawa, , Malawi

Site Status

Mangochi District Hospital

Mangochi, , Malawi

Site Status

Handeni District Hospital

Handeni, , Tanzania

Site Status

Korogwe District Hospital

Korogwe, , Tanzania

Site Status

Countries

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Kenya Malawi Tanzania

References

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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.

Reference Type DERIVED
PMID: 40018559 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36913959 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35156190 (View on PubMed)

Other Identifiers

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16.049

Identifier Type: -

Identifier Source: org_study_id

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