Improving PRegnancy Outcomes With Intermittent preVEntive Treatment in Africa

IPTp With Dihydroartemisinin-piperaquine and Azithromycin for Malaria, Sexually Transmitted and Reproductive Tract Infections in Pregnancy in High Sulphadoxine-pyrimethamine Resistance Areas in Kenya, Malawi and Tanzania

Sponsors

Lead Sponsor: Liverpool School of Tropical Medicine

Collaborator: University of Malawi College of Medicine
Kenya Medical Research Institute
Malawi-Liverpool-Wellcome Trust Clinical Research Programme
National Institute for Medical Research, Tanzania
Kilimanjaro Christian Medical Centre, Tanzania
University of Copenhagen
Centers for Disease Control and Prevention
London School of Hygiene and Tropical Medicine
University College, London
Tampere University
University of Bergen
University of Massachusetts, Worcester
University of Toronto
University of Melbourne
PATH
Foundation for Innovative New Diagnostics, Switzerland

Source Liverpool School of Tropical Medicine
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.

Detailed Description

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.

Overall Status Completed
Start Date 2018-03-29
Completion Date 2020-03-15
Primary Completion Date 2020-03-15
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Adverse pregnancy outcome 8 months
Secondary Outcome
Measure Time Frame
Composite of foetal loss and neonatal mortality 8 months
SGA-LBW-PT composite 6 months
SGA 6 months
LBW 6 months
PT 6 months
Neonatal length and stunting 8 months
Clinical malaria during pregnancy 6 months from randomisation
Malaria infection during pregnancy detected by microscopy and PCR 6 months from randomisation
Composite placental malaria detected by microscopy, by molecular methods or by histology 6 months from randomisation
Placental malaria detected by microscopy 6 months from randomisation
Placental malaria detected by molecular methods (PCR) 6 months from randomisation
Placental malaria detected by histology 6 months from randomisation
Maternal nutritional status 6 months from randomisation
Maternal anaemia during pregnancy and delivery 6 months from randomisation
Congenital anaemia 6 months from randomisation
Congenital malaria infection 6 months from randomisation
QTc-prolongation 6 months from randomisation
Congenital malformations 6 months from randomisation
Maternal mortality 8 months from randomisation
Other SAEs and AEs 8 months from randomisation
(History of) vomiting study drug 6 months from randomisation
Dizziness 6 months from randomisation
Gastrointestinal complaints 6 months from randomisation
Molecular markers of drug resistance in Plasmodium falciparum infections during pregnancy and delivery 6 months from randomisation
Presence of STIs/RTIs prior to delivery (syphilis, gonorrhoea, Chlamydia trachomatis, Trichomonas vaginalis, and bacterial vaginosis) 6 months from randomisation
Changes in macrolide resistance in Pneumococcus detected in maternal nasopharyngeal samples 6 months from randomisation
Changes in the colony composition of maternal vaginal microbiota, and intestinal microbiota of mother and infant. 6 months from randomisation
Enrollment 4680
Condition
Intervention

Intervention Type: Drug

Intervention Name: dihydroartemisinin-piperaquine

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

Arm Group Label: IPTp-DP

Other Name: Eurartesim

Intervention Type: Drug

Intervention Name: sulphadoxine-pyrimethamine

Description: 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

Arm Group Label: IPTp-SP

Other Name: Fansidar

Intervention Type: Drug

Intervention Name: dihydroartemisinin-piperaquine plus azithromycin

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

Arm Group Label: IPTp-DPAZ

Other Name: Eurartesim plus Zithromax

Eligibility

Criteria:

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

Gender:

Female

Gender Based:

Yes

Gender Description:

Pregnant female

Minimum Age:

16 Years

Maximum Age:

N/A

Healthy Volunteers:

Accepts Healthy Volunteers

Overall Official
Location
Facility:
Ahero Sud-countyHospital | Ahero, Kisumu, Kenya
Homa Bay County Hospital | Homa Bay, Kenya
Rabour Sub-county Hospital | Kisumu, Kenya
Chikwawa District Hospital | Chikwawa, Malawi
Mangochi District Hospital | Mangochi, Malawi
Handeni District Hospital | Handeni, Tanzania
Korogwe District Hospital | Korogwe, Tanzania
Location Countries

Kenya

Malawi

Tanzania

Verification Date

2020-06-01

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 3
Arm Group

Label: IPTp-SP

Type: Active Comparator

Description: 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

Label: IPTp-DP

Type: Experimental

Description: 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

Label: IPTp-DPAZ

Type: Experimental

Description: 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.

Acronym IMPROVE
Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Prevention

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description: 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.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact [email protected]. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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