Clinical Trial Results:
Immunogenicity and Safety of Quadrivalent Influenza Vaccine (VaxigripTetra™) in Pregnant Women
Summary
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EudraCT number |
2016-004763-40 |
Trial protocol |
FI |
Global end of trial date |
14 Jun 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
26 May 2019
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First version publication date |
26 May 2019
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
GQM14
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
U1111-1183-5650 | ||
Sponsors
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Sponsor organisation name |
Sanofi Pasteur
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Sponsor organisation address |
14 Espace Henry Vallée, Lyon, France, 69007
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Public contact |
Trial Transparency Team, Sanofi Pasteur, Contact-US@sanofi.com
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Scientific contact |
Trial Transparency Team, Sanofi Pasteur, Contact-US@sanofi.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
23 Nov 2018
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
14 Jun 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Immunogenicity:
To describe the immune response of VaxigripTetra and Vaxigrip, 21 days after vaccination in pregnant women.
Safety:
To describe the safety profile of one dose of VaxigripTetra or Vaxigrip, 21 days after vaccination in pregnant women.
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Protection of trial subjects |
Vaccinations were performed by qualified and trained study personnel. Subjects with allergy to any of the vaccine components were not vaccinated. After vaccination, subjects were also kept under clinical observation for 30 minutes to ensure their safety. Appropriate medical equipment were also available on site in case of any immediate allergic reactions.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
15 Sep 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Finland: 346
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Worldwide total number of subjects |
346
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EEA total number of subjects |
346
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
346
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted at 10 centers in Finland from 15 September 2017 to 26 January 2018. | |||||||||||||||||||||
Pre-assignment
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Screening details |
A total of 346 subjects who met all of the inclusion criteria and none of the exclusion criteria were enrolled and randomized in the study. | |||||||||||||||||||||
Period 1
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Period 1 title |
Overall Period
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Subject, Investigator, Assessor | |||||||||||||||||||||
Blinding implementation details |
The study was conducted in a blind observer manner. Neither the Investigator responsible for safety assessment, nor the subject knew which vaccine was administered.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Quadrivalent Influenza Vaccine (VaxigripTetra) | |||||||||||||||||||||
Arm description |
Pregnant women aged >= 18 years and who were in the late second/third trimester of pregnancy received a single dose of VaxigripTetra vaccine. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Sanofi Pasteur licensed quadrivalent influenza vaccine (split-virion, inactivated)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection in pre-filled syringe
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Routes of administration |
Intramuscular use, Subcutaneous use
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Dosage and administration details |
0.5 mL, intramuscular (IM) or deep subcutaneous (SC) injection, single dose on Day 0.
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Arm title
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Trivalent Influenza Vaccine (Vaxigrip) | |||||||||||||||||||||
Arm description |
Pregnant women aged >= 18 years and who were in the late second/third trimester of pregnancy received a single dose of Vaxigrip vaccine. | |||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||
Investigational medicinal product name |
Sanofi Pasteur licensed trivalent influenza vaccine (split-virion, inactivated)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection in pre-filled syringe
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Routes of administration |
Intramuscular use, Subcutaneous use
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Dosage and administration details |
0.5 mL, intramuscular (IM) or deep subcutaneous (SC) injection, single dose on Day 0.
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Baseline characteristics reporting groups
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Reporting group title |
Quadrivalent Influenza Vaccine (VaxigripTetra)
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Reporting group description |
Pregnant women aged >= 18 years and who were in the late second/third trimester of pregnancy received a single dose of VaxigripTetra vaccine. | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Trivalent Influenza Vaccine (Vaxigrip)
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Reporting group description |
Pregnant women aged >= 18 years and who were in the late second/third trimester of pregnancy received a single dose of Vaxigrip vaccine. | ||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Quadrivalent Influenza Vaccine (VaxigripTetra)
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Reporting group description |
Pregnant women aged >= 18 years and who were in the late second/third trimester of pregnancy received a single dose of VaxigripTetra vaccine. | ||
Reporting group title |
Trivalent Influenza Vaccine (Vaxigrip)
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Reporting group description |
Pregnant women aged >= 18 years and who were in the late second/third trimester of pregnancy received a single dose of Vaxigrip vaccine. | ||
Subject analysis set title |
Quadrivalent Influenza Vaccine (VaxigripTetra)
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Babies born to pregnant women aged >= 18 years, who were in the late second/third trimester of pregnancy received a single dose of VaxigripTetra vaccine.
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Subject analysis set title |
Trivalent Influenza Vaccine (Vaxigrip)
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Babies born to pregnant women aged >= 18 years, who were in the late second/third trimester of pregnancy received a single dose of Vaxigrip vaccine.
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End point title |
Hemagglutination Inhibition (HAI) Antibody Titers After Vaccination With Quadrivalent Influenza Vaccine (VaxigripTetra) or Trivalent Influenza Vaccine (Vaxigrip) [1] | ||||||||||||||||||||||||||||||||||||
End point description |
Serum antibody titers for the strains A/H1N1, A/H3N2, B1 and B2 were assessed by HAI assay. Antibody titers were expressed as geometric mean titers (GMTs). Analysis was performed on Per-Protocol Analysis set which included subjects who received one dose of any of the study vaccines and had no protocol deviations.
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End point type |
Primary
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End point timeframe |
Day 0 (Pre-vaccination) and Day 21 (Post-vaccination)
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Individual Antibody Titer Ratio After Vaccination With Quadrivalent Influenza Vaccine (VaxigripTetra) or Trivalent Influenza Vaccine (Vaxigrip) [2] | ||||||||||||||||||||||||
End point description |
Individual antibody titer ratio for the strains A/H1N1, A/H3N2, B1 and B2 were assessed by HAI assay. Antibody titer ratio were expressed as Day 21/Day 0. Analysis was performed on Per-Protocol Analysis set.
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End point type |
Primary
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End point timeframe |
Day 0 (Pre-vaccination) and Day 21 (Post-vaccination)
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Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects With Detectable Antibody Titer After Vaccination With Quadrivalent Influenza Vaccine (VaxigripTetra) or Trivalent Influenza Vaccine (Vaxigrip) [3] | ||||||||||||||||||||||||||||||||||||
End point description |
Detectable antibody titers for the strains A/H1N1, A/H3N2, B1 and B2 were assessed by HAI assay. Detectable antibody titer value was >=10 (1/dilution [1/dil]). Analysis was performed on Per-Protocol Analysis set.
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End point type |
Primary
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End point timeframe |
Day 0 (Pre-vaccination) and Day 21 (Post-vaccination)
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Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects With Antibody Titer >= 40 (1/Dilution) After Vaccination With Quadrivalent Influenza Vaccine (VaxigripTetra) or Trivalent Influenza Vaccine (Vaxigrip) [4] | ||||||||||||||||||||||||||||||||||||
End point description |
Antibody titer >= 40 (1/dilution) for the strains A/H1N1, A/H3N2, B1 and B2 were assessed by HAI assay. Analysis was performed on Per-Protocol Analysis set.
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End point type |
Primary
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End point timeframe |
Day 0 (Pre-vaccination) and Day 21 (Post-vaccination)
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Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Seroconversion or Significant Increase of Antibody Titers After Vaccination With Quadrivalent Influenza Vaccine (VaxigripTetra) or Trivalent Influenza Vaccine (Vaxigrip) [5] | ||||||||||||||||||||||||
End point description |
Seroconversion was defined as the pre-vaccination titer < 10 (1/dil) on Day 0 and post-vaccination titer >= 40 (1/dil) on Day 21, or significant increase was defined as the pre vaccination titer >=10 (1/dil) and >= 4-fold increase of post-injection titer on Day 21. Analysis was performed on Per-Protocol Analysis set.
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End point type |
Primary
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End point timeframe |
Day 0 (Pre-vaccination) and Day 21 (Post-vaccination)
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Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects Reporting Solicited Injection Site or Systemic Reactions After Vaccination With Quadrivalent Influenza Vaccine (VaxigripTetra) or Trivalent Influenza Vaccine (Vaxigrip) [6] | ||||||||||||||||||||||||||||||||||||||||||
End point description |
Percentage of subjects experiencing at least 1 solicited injection site reaction (pain, erythema, swelling, induration and ecchymosis) and at least 1 systemic reaction (fever, headache, malaise, myalgia, and shivering) were reported. Analysis was performed on safety analysis set which included all subjects who had received at least 1 dose of the study or control vaccine; all subjects had their safety analyzed according to the vaccine actually received.
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End point type |
Primary
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End point timeframe |
Day 0 to Day 7 (Post-vaccination)
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Notes [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Geometric Mean Ratio of the Hemagglutination-Inhibition Titers in Infants and Mothers at the Time of Delivery | ||||||||||||||||||||||||
End point description |
Geometric mean ratio of the Hemagglutination-Inhibition titers in infants and mothers for each strain at the time of delivery was reported. Analysis was performed on Other Immunogenicity Analysis Set which included subjects who received one dose of any of the study vaccines, delivered at least 2 weeks after injection and with available cord blood sample (BL) and mother BL at the time of delivery or at Visit 2 (Day 21) if delivery occurred during the time window of Visit 2 (Day 21).
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End point type |
Secondary
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End point timeframe |
At the time of Delivery (on average 103 day after vaccination)
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No statistical analyses for this end point |
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End point title |
Birth Outcomes | ||||||||||||||||||||||||||||||||||||
End point description |
Number of babies with different birth outcomes assessed by methods used in routine at the hospital. Analysis was performed on the Babies other Safety analysis set which included babies of the subjects from the other Safety analysis set (defined as the subset of subjects who received one dose of the study or control vaccine and delivered at least 2 weeks after vaccination).
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End point type |
Secondary
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End point timeframe |
At the time of Delivery (on average 103 day after vaccination)
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Adverse event (AE) data collected from Day 0 (pre-vaccination) up to date of delivery (on an average 103 day after vaccination)
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Adverse event reporting additional description |
Solicited adverse reaction (SAR): An AE, i.e.prelisted in electronic case report form (eCRF) and considered related to vaccination. SAR is an adverse drug reaction observed,reported under the conditions (nature and onset) prelisted (i.e.solicited) in eCRF. Unsolicited AE: an observed AE that does not fulfill conditions prelisted in eCRF. Safety set
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.0
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Reporting groups
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Reporting group title |
Quadrivalent Influenza Vaccine (VaxigripTetra)
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Reporting group description |
Pregnant women aged >= 18 years and in late second/third trimester of pregnancy received a single dose of VaxigripTetra vaccine. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Trivalent Influenza Vaccine (Vaxigrip)
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Reporting group description |
Pregnant women aged >= 18 years and in late second/third trimester of pregnancy received a single dose of Vaxigrip vaccine. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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20 Feb 2018 |
Corrections made to the following sections of the protocol: the objectives, endpoints, statistical methods and sample size. Recently available information regarding vaccine development and strains content was also added to background of IP. One additional month was allotted to the enrollment period. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |