A Study of Outcomes and Events of Interest in Pregnant Women, Neonates and Infants and of RSV Surveillance

Respiratory Syncytial Virus Infections Clinical Trial

— PEPNI  

Official title:

A Prospective Epidemiological Study of Pregnancy Outcomes and of Events of Interest in Pregnant Women, Neonates and Infants (PEPNI)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03614676
• Other study ID #: 207636
• Status: Completed
• Phase: N/A
• Start date: May 30, 2019
• Est. completion date: July 27, 2021

Study information

• Verified date: July 2023
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess pregnancy outcomes, and maternal, as well as neonatal events of interest in healthy pregnant women and their new-borns. The study will also determine incidence of lower respiratory tract illness (LRTI) caused by respiratory syncytial virus (RSV) in the new-borns during their first year of life.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4493
• Est. completion date: July 27, 2021
• Est. primary completion date: July 27, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• Healthy pregnant women 18-45years of age who are = 24 0/7 weeks GA at screening and = 27 6/7 weeks GA at Visit 1, as established by ultrasound examination and/or last menstrual period (LMP) date

• Women with pre-pregnancy body mass index (BMI) =18.5 and = 39.9 kg/m2.

• Women whose pregnancy is considered low risk, based on medical history, obstetric history, and clinical findings during the current pregnancy

• Women who had no significant findings (such as abnormal fetal morphology, amniotic fluid levels, placenta, or umbilical cord) observed during a Level 2 ultrasound (fetal morphology assessment).

• Human Immunodeficiency Virus (HIV) uninfected women who have been tested within the past year and have documented HIV negative test results.

• Individuals who give written or witnessed/thumb printed informed consent after the study has been explained according to local regulatory requirements.

• The informed consent given at screening should either include consent for both the mother's participation and participation of the infant after the infant's birth (if consistent with local regulations/guidelines), or consent for the mother's participation and expressed willingness to consider permitting the infant to take part after the infant has been born (if local regulations/guidelines require parent(s) to provide an additional informed consent after the infant's birth).

• Both mother and father should consent if local regulations/guidelines require it.

• Individuals who consent to have cord blood collected at delivery for the purpose of the study;

• Individuals who plan to reside in the study area for at least one year after delivery.

• Individuals who are in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator;

• Individuals who, in the opinion of the investigator can and will comprehend and comply with all study procedures

• Infants who were in utero at the time maternal (and paternal, if required) informed consent was given, and who are live-born.

• If local law requires it: Written or witnessed/thumb printed informed consent for study participation of the infant obtained from parent(s)/Legally Accepted Representative [LAR(s)] within 21 days of birth.

Exclusion Criteria:

• Individuals determined to have one of the following conditions associated with increased risk for a serious obstetrical complication

• Gestational hypertension;

• Gestational diabetes uncontrolled by diet and exercise;

• Pre-eclampsia or eclampsia;

• Multiple pregnancy;

• Intrauterine growth restriction;

• Placenta previa;

• Polyhydramnios;

• Oligohydramnios;

• Individuals determined to have (during the current pregnancy) one of the following infections or conditions associated with risk of adverse outcome:

• Known or suspected:

• Syphilis infection,

• Parvovirus B19,

• Rubella infection,

• primary herpes simplex infection,

• primary cytomegalovirus infection,

• varicella infection,

• Zika infection,

• Active tuberculosis infection,

• Incompetent cervix or cerclage

• Individuals who have any underlying condition or infection that would predispose them to increased risk for a serious obstetrical complication that is not mentioned above

• Individuals who have behavioural or cognitive impairment or psychiatric disease that, in the opinion of the investigator, could interfere with the subject's ability to participate in the study;

• Individuals who have known or suspected impairment of the immune system, an active autoimmune disorder that is not well-controlled, or who are receiving systemic immunosuppressive therapy;

• Individuals participating in any concurrent clinical trial during the current pregnancy;

• Individuals pregnant with a fetus with a confirmed or suspected major congenital anomaly at the time of enrolment.

• Child in care

Related Conditions & MeSH terms

• Respiratory Syncytial Virus Infections

Intervention

Procedure:
• Blood sample collection
Venous blood samples will be collected from the maternal subjects at Day 1 and Day 56 of the study and at delivery.
• Cord blood sample collection
Collection of cord blood samples from maternal subjects will occur, at delivery

Other:
• Maternal Diary Card
Completion of Diary Card about health by pregnant woman/ mother, from enrolment through week 6 post delivery.

Procedure:
• Nasal Swab collection
Collection of nasal swabs from infants with potential LRTIs, from birth to 12 months of age.

Other:
• Infant Diary Card
Completion of Diary Card about health of infant from birth to 12 months of age.

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires
Argentina	GSK Investigational Site	Mendoza
Argentina	GSK Investigational Site	Mendoza
Argentina	GSK Investigational Site	Rio Cuarto
Argentina	GSK Investigational Site	Villanueva- Guaymallen	Mendoza
Bangladesh	GSK Investigational Site	Dhaka
Bangladesh	GSK Investigational Site	Dhaka
Brazil	GSK Investigational Site	Belo Horizonte	Minas Gerais
Brazil	GSK Investigational Site	Ribeirão Preto	São Paulo
Brazil	GSK Investigational Site	Santa Maria	Rio Grande Do Sul
Colombia	GSK Investigational Site	Bogota
Colombia	GSK Investigational Site	Cali
Colombia	GSK Investigational Site	Medellin
Colombia	GSK Investigational Site	Medellin
Colombia	GSK Investigational Site	Santa Fe De Bogota
Colombia	GSK Investigational Site	Villavicencio
Malaysia	GSK Investigational Site	Alor Setar
Malaysia	GSK Investigational Site	Alor Setar
Malaysia	GSK Investigational Site	Kota Kinabalu
Malaysia	GSK Investigational Site	Kuala Lumpur
Malaysia	GSK Investigational Site	Kuching
Mexico	GSK Investigational Site	Durango
Mexico	GSK Investigational Site	Monterrey	Nuevo León
Mexico	GSK Investigational Site	Monterrey	Nuevo León
Mexico	GSK Investigational Site	Oaxaca
Panama	GSK Investigational Site	Chiriquí
Panama	GSK Investigational Site	Juán Diaz
Panama	GSK Investigational Site	La Chorrera
Panama	GSK Investigational Site	Panamá
Panama	GSK Investigational Site	Panama City
Philippines	GSK Investigational Site	Cebu
Philippines	GSK Investigational Site	Manila
Philippines	GSK Investigational Site	Manila
South Africa	GSK Investigational Site	Parow Valley
South Africa	GSK Investigational Site	Pretoria	Gauteng
South Africa	GSK Investigational Site	Soshanguve
Thailand	GSK Investigational Site	Bangkok
Thailand	GSK Investigational Site	Bangkok
Thailand	GSK Investigational Site	Chiang Mai

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Argentina,  Bangladesh,  Brazil,  Colombia,  Malaysia,  Mexico,  Panama,  Philippines,  South Africa,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Maternal Subjects With Pregnancy Outcomes	Pregnancy outcomes included: live birth with no congenital anomalies, live birth with congenital anomalies, fetal death/stillbirth loss at or after 22 weeks of gestation (antepartum stillbirth, Intrapartum stillbirth) with no congenital anomalies, fetal death/still birth loss at or after 22 weeks of gestation (antepartum stillbirth, Intrapartum stillbirth) with congenital anomalies, elective/therapeutic termination with no congenital anomalies, elective/therapeutic termination with congenital anomalies.	From Day 1 up to Day 42 post delivery
Primary	Number of Maternal Subjects With Pregnancy Related Events of Interest	Pregnancy related events of interest included: maternal death, hypertensive disorders of pregnancy including gestational hypertension, pre-eclampsia and pre-eclampsia with severe features (including eclampsia), antenatal bleeding (morbidly adherent placenta, placental abruption, Caesarean scar pregnancy, uterine rupture), postpartum haemorrhage, fetal growth restriction, dysfunctional labor (first stage of labor, second stage of labor), gestational diabetes mellitus, non-reassuring fetal status, pathways to preterm birth including premature preterm rupture of membranes, preterm labour, and provider initiated preterm birth, chorioamnionitis, oligohydramnios, polyhydramnios, gestational liver disease (intrahepatic cholestasis of pregnancy [ICP], acute fatty liver of pregnancy), and maternal sepsis.	From Day 1 up to Day 42 post-delivery
Primary	Number of Infant Subjects With Neonatal Events of Interest	Neonatal events of interest included: small for gestational age, low birth weight including very low birth weight, neonatal encephalopathy, congenital microcephaly (postnatally diagnosed, prenatally diagnosed), congenital anomalies [CA] (major external structural defects, internal structural defects, functional defects), neonatal death (neonatal death in a preterm live birth [gestational age greater than or equal to (=) 28 to less than (<) 37 weeks], neonatal death in a term live birth), neonatal infections, (blood stream infections, meningitis, respiratory infection), respiratory distress in the neonate, preterm birth, failure to thrive, large for gestational age, macrosomia, any other neonatal event considered by the investigator to be of concern (e.g. neurodevelopmental delay).	From birth up to Day 28 post-birth
Secondary	Number of Maternal Subjects With Pregnancy Related Events of Interest for Each Global Alignment of Immunization Safety Assessment (GAIA) Level of Diagnostic Certainty	Pregnancy related events of interest by GAIA level (Lv.) of diagnostic certainty (where applicable/feasible) range from Level 1 to Level 2 or 3 (Highest level of diagnostic certainty (1) to lowest level of diagnostic certainty (2 or 3)): maternal death, hypertensive disorders of pregnancy including gestational hypertension, pre-eclampsia and Pre-eclampsia with severe features (including eclampsia), antenatal bleeding (morbidly adherent placenta, placental abruption, Cesarean scar pregnancy, uterine rupture), postpartum haemorrhage, fetal growth restriction, dysfunctional labor, (first stage of labor, second stage of labor), gestational diabetes mellitus, non-reassuring fetal status, pathways to preterm birth including premature preterm rupture of membranes, preterm labour, and provider initiated preterm birth.	From Day 1 up to Day 42 post-delivery
Secondary	Number of Infant Subjects With Neonatal Events of Interest for Each GAIA Level of Diagnostic Certainty	Neonatal events of interest by GAIA level (Lv.) of diagnostic certainty, range from Level 1 to Level 4 or 5 (Highest level of diagnostic certainty (1) to lowest level of diagnostic certainty (4 or 5 based on the neonatal events)): small for gestational age, low birth weight including very low birth weight, neonatal encephalopathy, congenital microcephaly (postnatally diagnosed, prenatally diagnosed), congenital anomalies [CA] (major external structural defects, internal structural defects, functional defects), neonatal death (neonatal death in a preterm live birth [gestational age = 28 to <37 weeks], neonatal death in a term live birth), neonatal infections (blood stream infections, meningitis, respiratory infection, respiratory distress in the neonate, preterm birth, failure to thrive, large for gestational age, macrosomia, any other neonatal event considered by the investigator to be of concern (e.g. neurodevelopmental delay).	From birth through Day 28 of life
Secondary	Respiratory Syncytial Virus Type A (RSV-A) Neutralizing Antibody Titers in Maternal Blood	Serological assays for the determination of antibodies against RSV-A were performed by neutralization assay. The corresponding antibody titers were expressed Geometric Mean Titers (GMT) with 95% Confidence Interval (CI) in Estimated Dilution 60 (ED60) and were measured on blood samples collected from vaccinated maternal subjects.	At delivery
Secondary	RSV-A Neutralizing Antibodies Titers in Cord Blood	Serological assays for the determination of antibodies against RSV-A were performed by neutralization assay. The corresponding antibody titers were presented as GMTs, expressed in ED60. The antibodies were measured on the cord blood sample collected at delivery.	At delivery
Secondary	Incidence Rates of RSV Lower Respiratory Tract Infection (LRTI) or Severe LRTI or Very Severe LRTI for Infant Subjects as Defined by the LRTI Case Definition	The incidence rate was calculated by dividing the number of infant subjects reporting first episodes over the follow-up period, to the total person-years. LRTI Case definition by WHO (Modjarrad, 2016): LRTI is diagnosed when infant has history of cough OR difficulty in breathing AND SpO2 < 95%, OR RR increase AND Confirmed RSV infection. Severe LRTI is diagnosed when an infant with RSV LRTI has oxygen saturation <93% or lower chest wall drawing. Very severe LRTI is diagnosed when an infant with RSV LRTI has oxygen saturation <90%, OR inability to feed OR failure to respond / unconscious.	From birth up to 1 year of age
Secondary	Incidence Rates of Infant Subjects With RSV Hospitalizations	The incidence rate was calculated by dividing the number of subjects reporting first episodes over the follow-up period to the total person-years. RSV hospitalizations definition by WHO (Modjarrad, 2015): Infant has confirmed RSV infection AND hospitalized for acute medical condition.	From birth up to 1 year of age