Clinical trial NCT03208179: Improving PRegnancy Outcomes With Intermittent preVEntive Treatment in Africa
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pregnancy
Malaria in Pregnancy
Malaria
Keywords: Malaria in Pregnancy
Intermittent Preventive Treatment
IPTp
Lead sponsor: Liverpool School of Tropical Medicine
Sponsor class: OTHER
Collaborators: name: Kamuzu University of Health Sciences
name: Kenya Medical Research Institute
name: Malawi-Liverpool-Wellcome Trust Clinical Research Programme
name: National Institute for Medical Research, Tanzania
name: Kilimanjaro Christian Medical Centre, Tanzania
name: University of Copenhagen
name: Centers for Disease Control and Prevention
name: London School of Hygiene and Tropical Medicine
name: University College, London
name: Tampere University
name: University of Bergen
name: University of Massachusetts, Worcester
name: University of Toronto
name: University of Melbourne
name: Foundation for Innovative New Diagnostics, Switzerland
First posted: 2017-07-05
Enrollment: 4680
Sex: FEMALE
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Adverse pregnancy outcome
timeFrame: 8 months
Secondary outcomes:
measure: Composite of foetal loss and neonatal mortality
timeFrame: 8 months
measure: SGA-LBW-PT composite
timeFrame: 6 months
measure: SGA
timeFrame: 6 months
measure: LBW
timeFrame: 6 months
measure: PT
timeFrame: 6 months
measure: Neonatal length and stunting
timeFrame: 8 months
measure: Clinical malaria during pregnancy
timeFrame: 6 months from randomisation
measure: Malaria infection during pregnancy detected by microscopy and PCR
timeFrame: 6 months from randomisation
measure: Composite placental malaria detected by microscopy, by molecular methods or by histology
timeFrame: 6 months from randomisation
measure: Placental malaria detected by microscopy
timeFrame: 6 months from randomisation
measure: Placental malaria detected by molecular methods (PCR)
timeFrame: 6 months from randomisation
measure: Placental malaria detected by histology
timeFrame: 6 months from randomisation
measure: Maternal nutritional status
timeFrame: 6 months from randomisation
measure: Maternal anaemia during pregnancy and delivery
timeFrame: 6 months from randomisation
measure: Congenital anaemia
timeFrame: 6 months from randomisation
measure: Congenital malaria infection
timeFrame: 6 months from randomisation
measure: QTc-prolongation
timeFrame: 6 months from randomisation
measure: Congenital malformations
timeFrame: 6 months from randomisation
measure: Maternal mortality
timeFrame: 8 months from randomisation
measure: Other SAEs and AEs
timeFrame: 8 months from randomisation
measure: (History of) vomiting study drug
timeFrame: 6 months from randomisation
measure: Dizziness
timeFrame: 6 months from randomisation
measure: Gastrointestinal complaints
timeFrame: 6 months from randomisation
measure: Molecular markers of drug resistance in Plasmodium falciparum infections during pregnancy and delivery
timeFrame: 6 months from randomisation
measure: Presence of STIs/RTIs prior to delivery (syphilis, gonorrhoea, Chlamydia trachomatis, Trichomonas vaginalis, and bacterial vaginosis)
timeFrame: 6 months from randomisation
measure: Changes in macrolide resistance in Pneumococcus detected in maternal nasopharyngeal samples
timeFrame: 6 months from randomisation
measure: Changes in the colony composition of maternal vaginal microbiota, and intestinal microbiota of mother and infant.
timeFrame: 6 months from randomisation
Other outcomes:
Locations:
city: Ahero
country: Kenya
facility: Ahero Sud-countyHospital
state: Kisumu
city: Homa Bay
country: Kenya
facility: Homa Bay County Hospital
city: Kisumu
country: Kenya
facility: Rabour Sub-county Hospital
city: Chikwawa
country: Malawi
facility: Chikwawa District Hospital
city: Mangochi
country: Malawi
facility: Mangochi District Hospital
city: Handeni
country: Tanzania
facility: Handeni District Hospital
city: Korogwe
country: Tanzania
facility: Korogwe District Hospital
Study officials:
affiliation: Kenya Medical Research Institute
name: Simon K Kariuki, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kilimanjaro Christian Medical University College
name: Frank Mosha, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Institute for Medical Research
name: John Lusingu, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.