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The purpose of this study is to assess the safety of RefortrixTM (Tdap) when administered during pregnancy in a maternal immunization program in Brazil.
In this retrospective cohort study the safety of RefortrixTM (Tdap) administered during pregnancy as part of the National immunization program in Brazil will be assessed by comparing the risk of pre-defined adverse events before and after introduction of the RefortrixTM (Tdap) maternal immunization program.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Exposed cohort | Women, 18-45 years of age at the time of pregnancy, who delivered in the hospital (study centre) from May 2015 and who received one dose of Refortrix during 27 to 36 weeks of pregnancy (or as late as 20 days before delivery due date). |
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| Unexposed cohort | Women, 18-45 years of age at the time of pregnancy, who delivered in the hospital (study centre) before implementation of the maternal immunization program in Brazil in September 2014 and who did not receive Tdap vaccination during pregnancy. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Combined diphtheria, tetanus and tricomponent acellular pertussis vaccine [Refortrix (Tdap)] | Biological | Subjects were included in the Exposed cohort if they received Refortrix as part of the maternal immunization program in Brazil. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects Reporting Gestational Diabetes | Gestational diabetes was defined as: Onset or first recognition of abnormal glucose tolerance during pregnancy (the diagnosis is based on administration of glucose challenge test at 24-28 weeks of gestation). Includes Class A1: Euglycaemia achieved with diet and/or exercise and Class A2: Euglycaemia achieved with medication. | After week 27 of pregnancy |
| Number of Subjects Reporting Pregnancy-related Hypertension, Pre-eclampsia, Eclampsia, and HELLP Syndrome | Pregnancy-related hypertension is defined as: Blood pressure systolic higher than (>) 140 and/or diastolic > 90 millimetre of mercury (mmHg), documented in at least two separate measurements after 20 weeks of gestation, without proteinuria or other stigmata of pre-eclampsia, and returning to normal post-partum. Hypertension usually resolves by 12 weeks post-partum, included pre-eclampsia, eclampsia and haemolysis elevated liver enzymes low platelet (HELLP) Syndrome for this study. | After week 27 of pregnancy |
| Number of Subjects Reporting Pregnancy Hemorrhage | Pregnancy vaginal hemorrhage is defined as: excessive blood loss after delivery i.e. estimated blood loss in excess of 500 milliliters (ml) after vaginal delivery and estimated blood loss in excess of 1000 ml after Caesarean delivery. The other symptoms are higher than or equal to (≥) 10 percent (%) drop in hematocrit, need for blood transfusion, symptomatic hypotension, dizziness, pallor and oliguria. Vaginal or intrauterine hemorrhage that encompasses antepartum (i.e. bleeding from the genital tract after 24 weeks of gestation), intrapartum, and postpartum bleeding (i.e. within 24 hours post-delivery). A major obstetric hemorrhage is defined as blood loss from uterus or genital tract >1500 ml or a decrease. | After week 27 of pregnancy |
| Number of Subjects With Pre-specified Neonate-related Outcomes Resulting in Preterm Birth | Preterm birth is defined as: Birth before 37 weeks of gestation. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects Reporting Pregnancy-related Adverse Events (AEs) of Interest/Neonate-related Events up to Delivery | Pregnancy-related AEs of interest and neonate-related events are defined as: premature rupture of membranes, preterm premature rupture of membranes, premature uterine contraction, neonatal death, maternal death, still birth, neonatal hypoxic ischaemic encephalopathy. | After week 27 of pregnancy |
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Inclusion Criteria:
Inclusion criteria for the Exposed cohort:
Inclusion criteria for the Unexposed cohort:
Exclusion Criteria:
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The subjects who delivered in the study centre from May 2015 onwards will be considered as potentially exposed and those who delivered before September 2014 will be considered as potentially unexposed
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Santo André | São Paulo | 09060-650 | Brazil |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31216218 | Background | Sancovski M, Mesaros N, Feng Y, Ceregido MA, Luyts D, De Barros E. Safety of reduced antigen content diphtheria-tetanus-acellular pertussis vaccine when administered during pregnancy as part of the maternal immunization program in Brazil: a single center, observational, retrospective, cohort study. Hum Vaccin Immunother. 2019;15(12):2873-2881. doi: 10.1080/21645515.2019.1627161. Epub 2019 Jun 20. |
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A total of 2462 subjects were enrolled in the study in one center in Brazil.
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| ID | Title | Description |
|---|---|---|
| FG000 | Exposed Cohort | Women, 18-45 years of age at the time of pregnancy, who delivered in the hospital (study centre) from May 2015 and who received one dose of Refortrix during 27 to 36 weeks of pregnancy (or as late as 20 days before delivery due date). |
| FG001 | Unexposed Cohort |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 11, 2015 | Sep 4, 2019 |
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| From week 27 up to week 37 of pregnancy |
| Number of Subjects With Pre-specified Neonate-related Outcomes, Resulting in Neonates Small for Their Gestational Age | Small for gestational age is defined as: Birth weight less than (<) 10% for infants of same gestational age and gender in same population. | After week 27 of pregnancy |
| Number of Subjects Reporting Cases of Congenital Anomalies in the Neonates | Congenital anomalies include morphological, functional, chromosomal or genetic anomalies, regardless of whether detected at birth or not, the foetus is delivered dead or alive, or defects are identified by prenatal ultrasound, amniocentesis or examination of the products of conception. | From week 27 of pregnancy up to birth |
| Number of Subjects With Pregnancy-related AEs and Birth Outcomes Per Calendar Year | Pregnancy related AEs include: gestational diabetes, pregnancy-related hypertension, pre-eclampsia, eclampsia, HELLP Syndrome and pregnancy hemorrhage. Birth outcomes include: preterm birth and small for gestational age. | After week 27 of pregnancy |
Women, 18-45 years of age at the time of pregnancy, who delivered in the hospital (study centre) before implementation of the maternal immunization program in Brazil in September 2014 and who did not receive Tdap vaccination during pregnancy. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Exposed Cohort | Women, 18-45 years of age at the time of pregnancy, who delivered in the hospital (study centre) from May 2015 and who received one dose of Refortrix during 27 to 36 weeks of pregnancy (or as late as 20 days before delivery due date). |
| BG001 | Unexposed Cohort | Women, 18-45 years of age at the time of pregnancy, who delivered in the hospital (study centre) before implementation of the maternal immunization program in Brazil in September 2014 and who did not receive Tdap vaccination during pregnancy. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Subjects Reporting Gestational Diabetes | Gestational diabetes was defined as: Onset or first recognition of abnormal glucose tolerance during pregnancy (the diagnosis is based on administration of glucose challenge test at 24-28 weeks of gestation). Includes Class A1: Euglycaemia achieved with diet and/or exercise and Class A2: Euglycaemia achieved with medication. | Analysis was performed on the Total Cohort (TC), which included all the subjects enrolled in the study with symptom sheets filled-in. | Posted | Count of Participants | Participants | After week 27 of pregnancy |
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| Primary | Number of Subjects Reporting Pregnancy-related Hypertension, Pre-eclampsia, Eclampsia, and HELLP Syndrome | Pregnancy-related hypertension is defined as: Blood pressure systolic higher than (>) 140 and/or diastolic > 90 millimetre of mercury (mmHg), documented in at least two separate measurements after 20 weeks of gestation, without proteinuria or other stigmata of pre-eclampsia, and returning to normal post-partum. Hypertension usually resolves by 12 weeks post-partum, included pre-eclampsia, eclampsia and haemolysis elevated liver enzymes low platelet (HELLP) Syndrome for this study. | Analysis was performed on the Total Cohort (TC), which included all the subjects enrolled in the study with symptom sheets filled-in. | Posted | Count of Participants | Participants | After week 27 of pregnancy |
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| Primary | Number of Subjects Reporting Pregnancy Hemorrhage | Pregnancy vaginal hemorrhage is defined as: excessive blood loss after delivery i.e. estimated blood loss in excess of 500 milliliters (ml) after vaginal delivery and estimated blood loss in excess of 1000 ml after Caesarean delivery. The other symptoms are higher than or equal to (≥) 10 percent (%) drop in hematocrit, need for blood transfusion, symptomatic hypotension, dizziness, pallor and oliguria. Vaginal or intrauterine hemorrhage that encompasses antepartum (i.e. bleeding from the genital tract after 24 weeks of gestation), intrapartum, and postpartum bleeding (i.e. within 24 hours post-delivery). A major obstetric hemorrhage is defined as blood loss from uterus or genital tract >1500 ml or a decrease. | Analysis was performed on the Total Cohort (TC), which included all the subjects enrolled in the study with symptom sheets filled-in. | Posted | Count of Participants | Participants | After week 27 of pregnancy |
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| Primary | Number of Subjects With Pre-specified Neonate-related Outcomes Resulting in Preterm Birth | Preterm birth is defined as: Birth before 37 weeks of gestation. | Analysis was performed on the Total Cohort (TC), which included all the subjects enrolled in the study with symptom sheets filled-in. | Posted | Count of Participants | Participants | From week 27 up to week 37 of pregnancy |
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| Primary | Number of Subjects With Pre-specified Neonate-related Outcomes, Resulting in Neonates Small for Their Gestational Age | Small for gestational age is defined as: Birth weight less than (<) 10% for infants of same gestational age and gender in same population. | Analysis was performed on the Total Cohort (TC), which included all the subjects enrolled in the study with symptom sheets filled-in. | Posted | Count of Participants | Participants | After week 27 of pregnancy |
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| Secondary | Number of Subjects Reporting Pregnancy-related Adverse Events (AEs) of Interest/Neonate-related Events up to Delivery | Pregnancy-related AEs of interest and neonate-related events are defined as: premature rupture of membranes, preterm premature rupture of membranes, premature uterine contraction, neonatal death, maternal death, still birth, neonatal hypoxic ischaemic encephalopathy. | Analysis was performed on the Total Cohort (TC), which included all the subjects enrolled in the study with symptom sheets filled-in. | Posted | Count of Participants | Participants | After week 27 of pregnancy |
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| Secondary | Number of Subjects Reporting Cases of Congenital Anomalies in the Neonates | Congenital anomalies include morphological, functional, chromosomal or genetic anomalies, regardless of whether detected at birth or not, the foetus is delivered dead or alive, or defects are identified by prenatal ultrasound, amniocentesis or examination of the products of conception. | Analysis was performed on the Total Cohort (TC), which included all the subjects enrolled in the study with symptom sheets filled-in. | Posted | Count of Participants | Participants | From week 27 of pregnancy up to birth |
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| Secondary | Number of Subjects With Pregnancy-related AEs and Birth Outcomes Per Calendar Year | Pregnancy related AEs include: gestational diabetes, pregnancy-related hypertension, pre-eclampsia, eclampsia, HELLP Syndrome and pregnancy hemorrhage. Birth outcomes include: preterm birth and small for gestational age. | Analysis was performed on the Unexposed Cohort which included women pregnant before implementation of the maternal immunization program, who didn't receive Refortrix, the study vaccine. | Posted | Count of Participants | Participants | After week 27 of pregnancy |
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Entire study period (From week 27 of pregnancy up to birth).
During this retrospective, observational study safety data was not recorded/collected.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Unexposed Cohort | Women, 18-45 years of age at the time of pregnancy, who delivered in the hospital (study centre) before implementation of the maternal immunization program in Brazil in September 2014 and who did not receive Tdap vaccination during pregnancy. | 0 | 0 | 0 | 0 | 0 | 0 |
| EG001 | Exposed Cohort | Women, 18-45 years of age at the time of pregnancy, who delivered in the hospital (study centre) from May 2015 and who received one dose of Refortrix during 27 to 36 weeks of pregnancy (or as late as 20 days before delivery due date). | 0 | 0 | 0 | 0 | 0 | 0 |
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GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | 877-379-3718 | GSKClinicalSupportHD@gsk.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 1, 2017 | Sep 4, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| D004165 | Diphtheria |
| D000013 | Congenital Abnormalities |
| ID | Term |
|---|---|
| D003354 | Corynebacterium Infections |
| D000193 | Actinomycetales Infections |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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| ID | Term |
|---|---|
| D013745 | Tetanus Toxoid |
| ID | Term |
|---|---|
| D014121 | Toxoids |
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
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