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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03208179
Other study ID # 16.049
Secondary ID
Status Completed
Phase Phase 3
First received
Last updated
Start date March 29, 2018
Est. completion date March 15, 2020

Study information

Verified date June 2022
Source Liverpool School of Tropical Medicine
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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 information / eligibility

Status Completed
Enrollment 4680
Est. completion date March 15, 2020
Est. primary completion date March 15, 2020
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Female
Age group 16 Years and older
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

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

Locations

Country Name City State
Kenya Ahero Sud-countyHospital Ahero Kisumu
Kenya Homa Bay County Hospital Homa Bay
Kenya Rabour Sub-county Hospital Kisumu
Malawi Chikwawa District Hospital Chikwawa
Malawi Mangochi District Hospital Mangochi
Tanzania Handeni District Hospital Handeni
Tanzania Korogwe District Hospital Korogwe

Sponsors (16)

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

Countries where clinical trial is conducted

Kenya,  Malawi,  Tanzania, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Composite of foetal loss and neonatal mortality Composite of foetal loss (spontaneous abortion or stillbirth) and neonatal mortality 8 months
Secondary SGA-LBW-PT composite Composite of small for gestational age, low birth weight or preterm birth 6 months
Secondary SGA Small for gestational age using the new INTERGROWTH population reference's 10th percentile 6 months
Secondary LBW Low birth weight defined as a corrected birth weight below 2.5 kg 6 months
Secondary PT Preterm birth defined as birth at a gestational age above 28 weeks but less than 37 completed weeks 6 months
Secondary Neonatal length and stunting Neonatal length and stunting 8 months
Secondary Clinical malaria during pregnancy Incidence of clinical malaria during pregnancy 6 months from randomisation
Secondary Malaria infection during pregnancy detected by microscopy and PCR Prevalence and incidence of peripheral maternal (blood) malaria infection during pregnancy by microscopy and PCR 6 months from randomisation
Secondary Composite placental malaria detected by microscopy, by molecular methods or by histology Prevalence of placental malaria by microscopy, PCR and placental histology 6 months from randomisation
Secondary Placental malaria detected by microscopy Prevalence of placental malaria detected in maternal placental blood by microscopy 6 months from randomisation
Secondary Placental malaria detected by molecular methods (PCR) Prevalence of placental malaria detected in maternal placental blood by PCR 6 months from randomisation
Secondary Placental malaria detected by histology Prevalence of placental malaria detected in full placental section by histology 6 months from randomisation
Secondary Maternal nutritional status Changes in maternal nutritional status by MUAC and BMI. 6 months from randomisation
Secondary Maternal anaemia during pregnancy and delivery Prevalence and incidence of maternal anaemia (Hb < 11g/dl) at enrolment, last antenatal visit and delivery 6 months from randomisation
Secondary Congenital anaemia Prevalence of anaemia (Hb < 13g/dl) from newborn cord blood 6 months from randomisation
Secondary Congenital malaria infection Prevalence of malaria infection by microscopy or PCR from newborn cord blood 6 months from randomisation
Secondary QTc-prolongation 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. 6 months from randomisation
Secondary Congenital malformations Any visible external congenital abnormality on surface examination 6 months from randomisation
Secondary Maternal mortality 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. 8 months from randomisation
Secondary Other SAEs and AEs Incidence of AEs and SAEs 8 months from randomisation
Secondary (History of) vomiting study drug Prevalence and incidence of vomiting investigational product (IP) twice at the same IP administration visit 6 months from randomisation
Secondary Dizziness Prevalence of dizziness after a course of IP 6 months from randomisation
Secondary Gastrointestinal complaints Prevalence of gastrointestinal complaints after a course of IP 6 months from randomisation
Secondary Molecular markers of drug resistance in Plasmodium falciparum infections during pregnancy and delivery Prevalence and incidence of SP and artemisinin resistance markers from infection isolates after enrollment and at delivery 6 months from randomisation
Secondary Presence of STIs/RTIs prior to delivery (syphilis, gonorrhoea, Chlamydia trachomatis, Trichomonas vaginalis, and bacterial vaginosis) Prevalence and incidence of STIs/RTIs (syphilis, gonorrhoea, Chlamydia trachomatis, Trichomonas vaginalis, and bacterial vaginosis) at randomization and last antenatal visit prior to delivery 6 months from randomisation
Secondary Changes in macrolide resistance in Pneumococcus detected in maternal nasopharyngeal samples Prevalence and incidence of carriage of macrolide resistant pneumococcus at randomization and delivery 6 months from randomisation
Secondary Changes in the colony composition of maternal vaginal microbiota, and intestinal microbiota of mother and infant. Changes in maternal reproductive tract and gut microbiota from randomisation to last antenatal visit prior to delivery, and neonatal gut microbiota 6 months from randomisation
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