Improving PRegnancy Outcomes With Intermittent preVEntive Treatment in Africa
- Conditions
- PregnancyMalaria in PregnancyMalaria
- Interventions
- Drug: sulphadoxine-pyrimethamineDrug: dihydroartemisinin-piperaquine plus azithromycinDrug: dihydroartemisinin-piperaquine
- Registration Number
- NCT03208179
- Lead Sponsor
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 4680
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description IPTp-SP sulphadoxine-pyrimethamine 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 IPTp-DPAZ dihydroartemisinin-piperaquine plus azithromycin 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. IPTp-DP dihydroartemisinin-piperaquine 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
- Primary Outcome Measures
Name Time Method Adverse pregnancy outcome 8 months 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.
- Secondary Outcome Measures
Name Time Method LBW 6 months Low birth weight defined as a corrected birth weight below 2.5 kg
Placental malaria detected by molecular methods (PCR) 6 months from randomisation Prevalence of placental malaria detected in maternal placental blood by PCR
QTc-prolongation 6 months from randomisation QTcF-prolongation of more than 60ms between baseline DTcF prior to first dose of DP (+/- AZ) on day 0 and repeat QTcF 4 - 6 hrs after administration of 3rd dose of DP(+/- AZ) on day 2, or QTcF \> 480ms, 4 - 6 hours after on day 2 treatment administration. Only on the DP containing arms.
Congenital malformations 6 months from randomisation Any visible external congenital abnormality on surface examination
Other SAEs and AEs 8 months from randomisation Incidence of AEs and SAEs
(History of) vomiting study drug 6 months from randomisation Prevalence and incidence of vomiting investigational product (IP) twice at the same IP administration visit
Molecular markers of drug resistance in Plasmodium falciparum infections during pregnancy and delivery 6 months from randomisation Prevalence and incidence of SP and artemisinin resistance markers from infection isolates after enrollment and at delivery
Neonatal length and stunting 8 months Neonatal length and stunting
Maternal nutritional status 6 months from randomisation Changes in maternal nutritional status by MUAC and BMI.
Maternal anaemia during pregnancy and delivery 6 months from randomisation Prevalence and incidence of maternal anaemia (Hb \< 11g/dl) at enrolment, last antenatal visit and delivery
Congenital anaemia 6 months from randomisation Prevalence of anaemia (Hb \< 13g/dl) from newborn cord blood
Composite of foetal loss and neonatal mortality 8 months Composite of foetal loss (spontaneous abortion or stillbirth) and neonatal mortality
SGA-LBW-PT composite 6 months Composite of small for gestational age, low birth weight or preterm birth
SGA 6 months Small for gestational age using the new INTERGROWTH population reference's 10th percentile
Congenital malaria infection 6 months from randomisation Prevalence of malaria infection by microscopy or PCR from newborn cord blood
Gastrointestinal complaints 6 months from randomisation Prevalence of gastrointestinal complaints after a course of IP
PT 6 months Preterm birth defined as birth at a gestational age above 28 weeks but less than 37 completed weeks
Placental malaria detected by microscopy 6 months from randomisation Prevalence of placental malaria detected in maternal placental blood by microscopy
Placental malaria detected by histology 6 months from randomisation Prevalence of placental malaria detected in full placental section by histology
Clinical malaria during pregnancy 6 months from randomisation Incidence of clinical malaria during pregnancy
Malaria infection during pregnancy detected by microscopy and PCR 6 months from randomisation Prevalence and incidence of peripheral maternal (blood) malaria infection during pregnancy by microscopy and PCR
Composite placental malaria detected by microscopy, by molecular methods or by histology 6 months from randomisation Prevalence of placental malaria by microscopy, PCR and placental histology
Maternal mortality 8 months from randomisation The death of a woman while pregnant or within 42 days of termination of pregnancy, irrespective of the duration and site of the pregnancy, from any cause related to or aggravated by the pregnancy or its management but not from accidental or incidental causes.
Dizziness 6 months from randomisation Prevalence of dizziness after a course of IP
Changes in the colony composition of maternal vaginal microbiota, and intestinal microbiota of mother and infant. 6 months from randomisation Changes in maternal reproductive tract and gut microbiota from randomisation to last antenatal visit prior to delivery, and neonatal gut microbiota
Presence of STIs/RTIs prior to delivery (syphilis, gonorrhoea, Chlamydia trachomatis, Trichomonas vaginalis, and bacterial vaginosis) 6 months from randomisation Prevalence and incidence of STIs/RTIs (syphilis, gonorrhoea, Chlamydia trachomatis, Trichomonas vaginalis, and bacterial vaginosis) at randomization and last antenatal visit prior to delivery
Changes in macrolide resistance in Pneumococcus detected in maternal nasopharyngeal samples 6 months from randomisation Prevalence and incidence of carriage of macrolide resistant pneumococcus at randomization and delivery
Trial Locations
- Locations (7)
Korogwe District Hospital
🇹🇿Korogwe, Tanzania
Chikwawa District Hospital
🇲🇼Chikwawa, Malawi
Mangochi District Hospital
🇲🇼Mangochi, Malawi
Rabour Sub-county Hospital
🇰🇪Kisumu, Kenya
Ahero Sud-countyHospital
🇰🇪Ahero, Kisumu, Kenya
Handeni District Hospital
🇹🇿Handeni, Tanzania
Homa Bay County Hospital
🇰🇪Homa Bay, Kenya