Trial Outcomes & Findings for A Post-marketing, Observational, Retrospective Study to Assess the Safety of RefortrixTM (Tdap) When Administered During Pregnancy in a Maternal Immunization Program in Brazil. (NCT NCT02757950)

NCT ID: NCT02757950

Last Updated: 2019-10-01

Results Overview

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.

• Recruitment status: COMPLETED
• Target enrollment: 2462 participants
• Primary outcome timeframe: After week 27 of pregnancy
• Results posted on: 2019-10-01

Participant Flow

A total of 2462 subjects were enrolled in the study in one center in Brazil.

Participant milestones

Measure	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).	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.
Overall Study STARTED	1203	1259
Overall Study COMPLETED	1199	1248
Overall Study NOT COMPLETED	4	11

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Exposed Cohort n=1203 Participants 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).	Unexposed Cohort n=1259 Participants 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.	Total n=2462 Participants Total of all reporting groups
Age, Continuous	26.49 Years STANDARD_DEVIATION 6.15 • n=1203 Participants	26.28 Years STANDARD_DEVIATION 6.24 • n=1259 Participants	26.38 Years STANDARD_DEVIATION 6.20 • n=2462 Participants
Sex: Female, Male Female	1203 Participants n=1203 Participants	1259 Participants n=1259 Participants	2462 Participants n=2462 Participants
Sex: Female, Male Male	0 Participants n=1203 Participants	0 Participants n=1259 Participants	0 Participants n=2462 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: After week 27 of pregnancy

Population: Analysis was performed on the Total Cohort (TC), which included all the subjects enrolled in the study with symptom sheets filled-in.

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.

Outcome measures

Measure	Exposed Cohort n=1199 Participants 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).	Unexposed Cohort n=1259 Participants 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.
Number of Subjects Reporting Gestational Diabetes	10 Participants	22 Participants

PRIMARY outcome

Timeframe: After week 27 of pregnancy

Population: Analysis was performed on the Total Cohort (TC), which included all the subjects enrolled in the study with symptom sheets filled-in.

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.

Outcome measures

Measure	Exposed Cohort n=1199 Participants 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).	Unexposed Cohort n=1259 Participants 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.
Number of Subjects Reporting Pregnancy-related Hypertension, Pre-eclampsia, Eclampsia, and HELLP Syndrome Pregnancy-related hypertension	11 Participants	31 Participants
Number of Subjects Reporting Pregnancy-related Hypertension, Pre-eclampsia, Eclampsia, and HELLP Syndrome Pre-eclampsia	10 Participants	30 Participants
Number of Subjects Reporting Pregnancy-related Hypertension, Pre-eclampsia, Eclampsia, and HELLP Syndrome Eclampsia	2 Participants	0 Participants
Number of Subjects Reporting Pregnancy-related Hypertension, Pre-eclampsia, Eclampsia, and HELLP Syndrome HELLP syndrome	0 Participants	1 Participants

PRIMARY outcome

Timeframe: After week 27 of pregnancy

Population: Analysis was performed on the Total Cohort (TC), which included all the subjects enrolled in the study with symptom sheets filled-in.

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.

Outcome measures

Measure	Exposed Cohort n=1199 Participants 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).	Unexposed Cohort n=1259 Participants 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.
Number of Subjects Reporting Pregnancy Hemorrhage	4 Participants	19 Participants

PRIMARY outcome

Timeframe: From week 27 up to week 37 of pregnancy

Population: Analysis was performed on the Total Cohort (TC), which included all the subjects enrolled in the study with symptom sheets filled-in.

Preterm birth is defined as: Birth before 37 weeks of gestation.

Outcome measures

Measure	Exposed Cohort n=1199 Participants 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).	Unexposed Cohort n=1259 Participants 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.
Number of Subjects With Pre-specified Neonate-related Outcomes Resulting in Preterm Birth	64 Participants	121 Participants

PRIMARY outcome

Timeframe: After week 27 of pregnancy

Population: Analysis was performed on the Total Cohort (TC), which included all the subjects enrolled in the study with symptom sheets filled-in.

Small for gestational age is defined as: Birth weight less than (<) 10% for infants of same gestational age and gender in same population.

Outcome measures

Measure	Exposed Cohort n=1199 Participants 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).	Unexposed Cohort n=1259 Participants 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.
Number of Subjects With Pre-specified Neonate-related Outcomes, Resulting in Neonates Small for Their Gestational Age	69 Participants	62 Participants

SECONDARY outcome

Timeframe: After week 27 of pregnancy

Population: Analysis was performed on the Total Cohort (TC), which included all the subjects enrolled in the study with symptom sheets filled-in.

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.

Outcome measures

Measure	Exposed Cohort n=1199 Participants 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).	Unexposed Cohort n=1259 Participants 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.
Number of Subjects Reporting Pregnancy-related Adverse Events (AEs) of Interest/Neonate-related Events up to Delivery Premature rupture of membranes	190 Participants	261 Participants
Number of Subjects Reporting Pregnancy-related Adverse Events (AEs) of Interest/Neonate-related Events up to Delivery Preterm premature rupture of membranes	17 Participants	36 Participants
Number of Subjects Reporting Pregnancy-related Adverse Events (AEs) of Interest/Neonate-related Events up to Delivery Premature uterine contractions	32 Participants	54 Participants
Number of Subjects Reporting Pregnancy-related Adverse Events (AEs) of Interest/Neonate-related Events up to Delivery Neonatal death	0 Participants	8 Participants
Number of Subjects Reporting Pregnancy-related Adverse Events (AEs) of Interest/Neonate-related Events up to Delivery Maternal death	0 Participants	0 Participants
Number of Subjects Reporting Pregnancy-related Adverse Events (AEs) of Interest/Neonate-related Events up to Delivery Still births	1 Participants	6 Participants
Number of Subjects Reporting Pregnancy-related Adverse Events (AEs) of Interest/Neonate-related Events up to Delivery Neonatal hypoxic ischaemic encephalopathy	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From week 27 of pregnancy up to birth

Population: Analysis was performed on the Total Cohort (TC), which included all the subjects enrolled in the study with symptom sheets filled-in.

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.

Outcome measures

Measure	Exposed Cohort n=1199 Participants 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).	Unexposed Cohort n=1259 Participants 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.
Number of Subjects Reporting Cases of Congenital Anomalies in the Neonates	3 Participants	22 Participants

SECONDARY outcome

Timeframe: After week 27 of pregnancy

Population: 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.

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.

Outcome measures

Measure	Exposed Cohort n=633 Participants 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).	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.
Number of Subjects With Pregnancy-related AEs and Birth Outcomes Per Calendar Year Gestational diabetes, Sep2012-Aug2013	10 Participants	—
Number of Subjects With Pregnancy-related AEs and Birth Outcomes Per Calendar Year Gestational diabetes, Sep2013-Aug2014	12 Participants	—
Number of Subjects With Pregnancy-related AEs and Birth Outcomes Per Calendar Year Pregnancy-related hypertension, Sep2012-Aug2013	14 Participants	—
Number of Subjects With Pregnancy-related AEs and Birth Outcomes Per Calendar Year Pregnancy-related hypertension, Sep2013-Aug2014	17 Participants	—
Number of Subjects With Pregnancy-related AEs and Birth Outcomes Per Calendar Year Vaginal hemorrhage, Sep2012-Aug2013	16 Participants	—
Number of Subjects With Pregnancy-related AEs and Birth Outcomes Per Calendar Year Vaginal hemorrhage, Sep2013-Aug2014	3 Participants	—
Number of Subjects With Pregnancy-related AEs and Birth Outcomes Per Calendar Year Preterm birth, Sep2012-Aug2013	66 Participants	—
Number of Subjects With Pregnancy-related AEs and Birth Outcomes Per Calendar Year Preterm birth, Sep2013-Aug2014	55 Participants	—
Number of Subjects With Pregnancy-related AEs and Birth Outcomes Per Calendar Year Small for gestational age, Sep2012-Aug2013	31 Participants	—
Number of Subjects With Pregnancy-related AEs and Birth Outcomes Per Calendar Year Small for gestational age, Sep2013-Aug2014	31 Participants	—
Number of Subjects With Pregnancy-related AEs and Birth Outcomes Per Calendar Year Pre-Eclampsia, Sep2012-Aug2013	13 Participants	—
Number of Subjects With Pregnancy-related AEs and Birth Outcomes Per Calendar Year Pre-Eclampsia, Sep2013-Aug 2014	17 Participants	—
Number of Subjects With Pregnancy-related AEs and Birth Outcomes Per Calendar Year Eclampsia, Sep2012-Aug2013	0 Participants	—
Number of Subjects With Pregnancy-related AEs and Birth Outcomes Per Calendar Year Eclampsia, Sep2013-Aug 2014	0 Participants	—
Number of Subjects With Pregnancy-related AEs and Birth Outcomes Per Calendar Year HELLP Syndrome, Sep2012-Aug2013	1 Participants	—
Number of Subjects With Pregnancy-related AEs and Birth Outcomes Per Calendar Year HELLP Syndrome, Sep2013-Aug 2014	0 Participants	—

Adverse Events

Unexposed Cohort

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Exposed Cohort

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

GSK Clinical Trials

GlaxoSmithKline

Phone: 877-379-3718

Email: GSKClinicalSupportHD@gsk.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER