Back to resultsCoadministration of Measles-rubella and Rotavirus Vaccines
Primary Purpose
Measles Antibody Seroconversion, Rubella Antibody Seroconversion, Rotavirus Geometric Mean Titer (GMT)
Status
Completed
Phase
Phase 4
Locations
Bangladesh
Study Type
Interventional
Intervention
Rotarix vaccine
measles-rubella vaccine
Sponsored by
About this trial
This is an interventional prevention trial for Measles Antibody Seroconversion focused on measuring rotavirus
Eligibility Criteria
Inclusion Criteria:
- Child 9 months of age eligible for measles-rubella vaccination
- documented evidence of a primary rotavirus vaccine series with first dose between 6 and 10 weeks of age and second dose at least 4 weeks after first dose
- healthy infants free of chronic or serious medical condition as determined by history and physical examination at time of study enrollment
- parents/guardians of each participant are able to understand and follow study procedures and agree to participate in study by providing signed informed consent
Exclusion Criteria:
- hypersensitivity to any component of measles-rubella or Rotarix vaccine which would preclude administration of the vaccine
- history of intussusception, intestinal malformations, or abdominal surgery
- known history of measles and/or rubella disease
- history of previous receipt of measles and/or rubella vaccine
- use of any immunosuppressive drugs or immunoglobulin and/or blood products since birth or anticipated during study period
- current enrolment in any other intervention trial or use of any investigational drug or vaccine throughout the study period
- any participant who reports planning to leave the study area before the completion of the study
- acute diarrhea (defined as ≥3 loose stools within a 24-hour period) or vomiting (defined as projectile vomiting or any vomiting at the discretion of the clinician) at the time of enrollment or within the last 24 hours
- acute febrile illness (defined as a temperature of ≥38°C) at the time of enrollment.
Sites / Locations
- ICDDR,B
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
measles-rubella and rotavirus vaccines
measles-rubella vaccine
Arm Description
receive one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine and one 1.0 ml dose of oral Rotarix vaccine at 9 months of age
receive one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine at 9 months of age
Outcomes
Primary Outcome Measures
Percentage/Number of Subjects With Seroprotection for Measles Virus Serum Neutralization Antibodies
Detected by plaque reduction neutralization test (PRNT).
Seroprotection defined as measles serum antibody concentration >=1:120 8 weeks post vaccination. Assays were standardized using WHO Second International Standard for measles antibody containing 5000 mIU/ml, which enables the 50% neutralizing antibody end-point dose (titer, ND50) of test samples to be transformed to antibody concentrations in terms of mIU/ml. The analytical cut-off value in this assay was ND50 < 1/8; this was the lowest dilution at which sera were tested.
Percentage/Number of Subjects With Seroprotection for Anti-measles Virus Immunoglobulin G (IgG)
Used commercially available indirect enzyme-linked IgG immunoassays (EIAs; Wampole Laboratories, Princeton, New Jersey). An index standard ratio (ISR) of ≥1.10 on both runs of the respective assay was considered evidence of seropositivity for measles virus. All measles virus and rubella virus assays were performed at the National Measles and Rubella Reference Laboratories, Measles, Mumps, Rubella, and Herpesviruses Branch, Division of Viral Diseases, Centers for Disease Control and Prevention (Atlanta, Georgia).
Secondary Outcome Measures
Percentage/Number of Subjects With Seroconversion for Anti-rubella Virus Immunoglobulin G (IgG)
Used commercially available indirect enzyme-linked IgG immunoassays (EIAs; Wampole Laboratories, Princeton, New Jersey). An index standard ratio (ISR) of ≥1.10 on both runs of the respective assay was considered evidence of seropositivity for rubella virus. An ISR of at least 1.10 represents 10 IU/mL of rubella virus antibody, consistent with a protective level.All measles virus and rubella virus assays were performed at the National Measles and Rubella Reference Laboratories, Measles, Mumps, Rubella, and Herpesviruses Branch, Division of Viral Diseases, Centers for Disease Control and Prevention (Atlanta, Georgia).
Geometric Mean Concentration (GMC) for Anti-rubella Virus Immunoglobulin G (IgG)
Used commercially available indirect enzyme-linked IgG immunoassays (EIAs; Wampole Laboratories, Princeton, New Jersey). An index standard ratio (ISR) of ≥1.10 on both runs of the respective assay was considered evidence of seropositivity for rubella virus. An ISR of at least 1.10 represents 10 IU/mL of rubella virus antibody, consistent with a protective level.All measles virus and rubella virus assays were performed at the National Measles and Rubella Reference Laboratories, Measles, Mumps, Rubella, and Herpesviruses Branch, Division of Viral Diseases, Centers for Disease Control and Prevention (Atlanta, Georgia).
Percentage/Number of Subjects Seropositive for Anti-rotavirus Immunoglobulin A (IgA)
Antirotavirus immunoglobulin A (IgA) and IgG were measured by enzyme-linked immunosorbent assay at the Laboratory of Specialized Clinical Studies at the Cincinnati Children's Hospital Medical Center (Cincinnati, Ohio). A standard serum pool was used to determine arbitrary units of rotavirus IgA or IgG in each sample. A subject was considered seropositive if the IgA or IgG rotavirus antibody concentration was ≥20 U/mL.
Geometric Mean Titer (GMT) of Anti-rotavirus Immunoglobulin A (IgA)
Antirotavirus immunoglobulin A (IgA) and IgG were measured by enzyme-linked immunosorbent assay at the Laboratory of Specialized Clinical Studies at the Cincinnati Children's Hospital Medical Center (Cincinnati, Ohio). A standard serum pool was used to determine arbitrary units of rotavirus IgA or IgG in each sample. Rotavirus IgA and IgG values of <20 U/mL are converted to 10 U/mL for calculation purposes.
Percentage/Number of Subjects Seropositive for Anti-rotavirus Immunoglobulin G (IgG)
Antirotavirus immunoglobulin A (IgA) and IgG were measured by enzyme-linked immunosorbent assay at the Laboratory of Specialized Clinical Studies at the Cincinnati Children's Hospital Medical Center (Cincinnati, Ohio). A standard serum pool was used to determine arbitrary units of rotavirus IgA or IgG in each sample. A subject was considered seropositive if the IgA or IgG rotavirus antibody concentration was ≥20 U/mL.
Geometric Mean Titer (GMT) of Anti-rotavirus Immunoglobulin G (IgG)
Antirotavirus immunoglobulin A (IgA) and IgG were measured by enzyme-linked immunosorbent assay at the Laboratory of Specialized Clinical Studies at the Cincinnati Children's Hospital Medical Center (Cincinnati, Ohio). A standard serum pool was used to determine arbitrary units of rotavirus IgA or IgG in each sample. Rotavirus IgA and IgG values of <20 U/mL are converted to 10 U/mL for calculation purposes.
Percentage/Number of Subjects With Seroconversion for Anti-rotavirus Immunoglobulin A (IgA)
Antirotavirus immunoglobulin A (IgA) and IgG were measured by enzyme-linked immunosorbent assay at the Laboratory of Specialized Clinical Studies at the Cincinnati Children's Hospital Medical Center (Cincinnati, Ohio). A standard serum pool was used to determine arbitrary units of rotavirus IgA or IgG in each sample. A subject was considered seropositive if the IgA or IgG rotavirus antibody concentration was ≥20 U/mL.
Percentage/Number of Subjects With Seroconversion for Anti-rotavirus Immunoglobulin G (IgG)
Antirotavirus immunoglobulin A (IgA) and IgG were measured by enzyme-linked immunosorbent assay at the Laboratory of Specialized Clinical Studies at the Cincinnati Children's Hospital Medical Center (Cincinnati, Ohio). A standard serum pool was used to determine arbitrary units of rotavirus IgA or IgG in each sample. A subject was considered seropositive if the IgA or IgG rotavirus antibody concentration was ≥20 U/mL.
Number/Percentage of Subjects Experiencing Immediate Post-vaccination Reactions Following Administration of Vaccine
Immediate reactogenicity was defined as local or systemic reactions occurring directly and up to 30 minutes after vaccine receipt, with an emphasis on allergic reactions.
Number/Percentage of Subjects Experiencing Solicited Adverse Events
Solicited non-serious adverse events were collected based on recall at study visits 2 (Day 4) through 5 (Day 14) following administration of Rotarix® vaccine. They included diarrhea, fever, vomiting, loss of appetite, irritability, and intussusception. Adverse events were graded for severity and relationship to vaccine.
Number/Percentage of Subjects Experiencing Unsolicited Non-serious Adverse Events
Solicited non-serious adverse events were collected based on recall at study visits 2 (Day 4) through 5 (Day 14) following administration of Rotarix® vaccine. Adverse events were graded for severity and relationship to vaccine.
Number/Percentage of Subjects Experiencing Serious Adverse Events
An adverse event (AE) or suspected AE was considered "serious" if it resulted in any of the following outcomes:
Death
A life-threatening AE (the term "life-threatening" in the definition of "serious" refers to an event in which the patient was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe)
Inpatient hospitalization or prolongation of existing hospitalization
A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions
Important medical events that may not result in death, be life threatening, or require hospitalization would have been considered severe adverse events when, based upon appropriate medical judgment, they may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes listed in this definition.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01700621
Brief Title
Coadministration of Measles-rubella and Rotavirus Vaccines
Official Title
Non-interference and Safety of Concomitant Administration of Measles-rubella and Rotavirus Vaccines at 9 Months of Age in Rural Bangladesh
Study Type
Interventional
2. Study Status
Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
January 2013 (undefined)
Primary Completion Date
September 2013 (Actual)
Study Completion Date
September 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PATH
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The investigators aim to establish the non-inferiority of concomitant administration of measles-rubella and rotavirus vaccines to measles-rubella vaccine given alone in terms of measles seroconversion rates. The primary study hypothesis is the measles seroconversion rate as defined by the percentage of children seroconverting to measles with a measles serum antibody concentration of >=1:120 at 8 weeks post vaccination after the concomitant administration of measles-rubella and rotavirus vaccines is non-inferior to that obtained when measles-rubella vaccine is given alone in children 9 months of age who have received a primary rotavirus vaccine series with the first dose between 6 and 10 weeks and the second at least 4 weeks later and are seronegative for measles antibody in the pre-vaccination sample.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Measles Antibody Seroconversion, Rubella Antibody Seroconversion, Rotavirus Geometric Mean Titer (GMT), Rotavirus Immunoglobulin A (IgA) Seropositivity
Keywords
rotavirus
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
482 (Actual)
8. Arms, Groups, and Interventions
Arm Title
measles-rubella and rotavirus vaccines
Arm Type
Experimental
Arm Description
receive one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine and one 1.0 ml dose of oral Rotarix vaccine at 9 months of age
Arm Title
measles-rubella vaccine
Arm Type
Active Comparator
Arm Description
receive one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine at 9 months of age
Intervention Type
Biological
Intervention Name(s)
Rotarix vaccine
Other Intervention Name(s)
rotavirus vaccine
Intervention Description
one 1.0 ml dose of oral rotavirus vaccine at 9 months of age
Intervention Type
Biological
Intervention Name(s)
measles-rubella vaccine
Other Intervention Name(s)
Measles-Rubella Virus Vaccine Live US Pharmacopeia (USP)
Intervention Description
one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine
Primary Outcome Measure Information:
Title
Percentage/Number of Subjects With Seroprotection for Measles Virus Serum Neutralization Antibodies
Description
Detected by plaque reduction neutralization test (PRNT).
Seroprotection defined as measles serum antibody concentration >=1:120 8 weeks post vaccination. Assays were standardized using WHO Second International Standard for measles antibody containing 5000 mIU/ml, which enables the 50% neutralizing antibody end-point dose (titer, ND50) of test samples to be transformed to antibody concentrations in terms of mIU/ml. The analytical cut-off value in this assay was ND50 < 1/8; this was the lowest dilution at which sera were tested.
Time Frame
8 weeks post vaccination
Title
Percentage/Number of Subjects With Seroprotection for Anti-measles Virus Immunoglobulin G (IgG)
Description
Used commercially available indirect enzyme-linked IgG immunoassays (EIAs; Wampole Laboratories, Princeton, New Jersey). An index standard ratio (ISR) of ≥1.10 on both runs of the respective assay was considered evidence of seropositivity for measles virus. All measles virus and rubella virus assays were performed at the National Measles and Rubella Reference Laboratories, Measles, Mumps, Rubella, and Herpesviruses Branch, Division of Viral Diseases, Centers for Disease Control and Prevention (Atlanta, Georgia).
Time Frame
8 weeks post vaccination
Secondary Outcome Measure Information:
Title
Percentage/Number of Subjects With Seroconversion for Anti-rubella Virus Immunoglobulin G (IgG)
Description
Used commercially available indirect enzyme-linked IgG immunoassays (EIAs; Wampole Laboratories, Princeton, New Jersey). An index standard ratio (ISR) of ≥1.10 on both runs of the respective assay was considered evidence of seropositivity for rubella virus. An ISR of at least 1.10 represents 10 IU/mL of rubella virus antibody, consistent with a protective level.All measles virus and rubella virus assays were performed at the National Measles and Rubella Reference Laboratories, Measles, Mumps, Rubella, and Herpesviruses Branch, Division of Viral Diseases, Centers for Disease Control and Prevention (Atlanta, Georgia).
Time Frame
8 weeks post vaccination
Title
Geometric Mean Concentration (GMC) for Anti-rubella Virus Immunoglobulin G (IgG)
Description
Used commercially available indirect enzyme-linked IgG immunoassays (EIAs; Wampole Laboratories, Princeton, New Jersey). An index standard ratio (ISR) of ≥1.10 on both runs of the respective assay was considered evidence of seropositivity for rubella virus. An ISR of at least 1.10 represents 10 IU/mL of rubella virus antibody, consistent with a protective level.All measles virus and rubella virus assays were performed at the National Measles and Rubella Reference Laboratories, Measles, Mumps, Rubella, and Herpesviruses Branch, Division of Viral Diseases, Centers for Disease Control and Prevention (Atlanta, Georgia).
Time Frame
8 weeks post vaccination
Title
Percentage/Number of Subjects Seropositive for Anti-rotavirus Immunoglobulin A (IgA)
Description
Antirotavirus immunoglobulin A (IgA) and IgG were measured by enzyme-linked immunosorbent assay at the Laboratory of Specialized Clinical Studies at the Cincinnati Children's Hospital Medical Center (Cincinnati, Ohio). A standard serum pool was used to determine arbitrary units of rotavirus IgA or IgG in each sample. A subject was considered seropositive if the IgA or IgG rotavirus antibody concentration was ≥20 U/mL.
Time Frame
Visit 1 (pre-vaccination) and 8 weeks post vaccination
Title
Geometric Mean Titer (GMT) of Anti-rotavirus Immunoglobulin A (IgA)
Description
Antirotavirus immunoglobulin A (IgA) and IgG were measured by enzyme-linked immunosorbent assay at the Laboratory of Specialized Clinical Studies at the Cincinnati Children's Hospital Medical Center (Cincinnati, Ohio). A standard serum pool was used to determine arbitrary units of rotavirus IgA or IgG in each sample. Rotavirus IgA and IgG values of <20 U/mL are converted to 10 U/mL for calculation purposes.
Time Frame
Visit 1 (pre-vaccination) and 8 weeks post vaccination
Title
Percentage/Number of Subjects Seropositive for Anti-rotavirus Immunoglobulin G (IgG)
Description
Antirotavirus immunoglobulin A (IgA) and IgG were measured by enzyme-linked immunosorbent assay at the Laboratory of Specialized Clinical Studies at the Cincinnati Children's Hospital Medical Center (Cincinnati, Ohio). A standard serum pool was used to determine arbitrary units of rotavirus IgA or IgG in each sample. A subject was considered seropositive if the IgA or IgG rotavirus antibody concentration was ≥20 U/mL.
Time Frame
Visit 1 (pre-vaccination) and 8 weeks post vaccination
Title
Geometric Mean Titer (GMT) of Anti-rotavirus Immunoglobulin G (IgG)
Description
Antirotavirus immunoglobulin A (IgA) and IgG were measured by enzyme-linked immunosorbent assay at the Laboratory of Specialized Clinical Studies at the Cincinnati Children's Hospital Medical Center (Cincinnati, Ohio). A standard serum pool was used to determine arbitrary units of rotavirus IgA or IgG in each sample. Rotavirus IgA and IgG values of <20 U/mL are converted to 10 U/mL for calculation purposes.
Time Frame
Visit 1 (pre-vaccination) and 8 weeks post vaccination
Title
Percentage/Number of Subjects With Seroconversion for Anti-rotavirus Immunoglobulin A (IgA)
Description
Antirotavirus immunoglobulin A (IgA) and IgG were measured by enzyme-linked immunosorbent assay at the Laboratory of Specialized Clinical Studies at the Cincinnati Children's Hospital Medical Center (Cincinnati, Ohio). A standard serum pool was used to determine arbitrary units of rotavirus IgA or IgG in each sample. A subject was considered seropositive if the IgA or IgG rotavirus antibody concentration was ≥20 U/mL.
Time Frame
8 weeks post vaccination
Title
Percentage/Number of Subjects With Seroconversion for Anti-rotavirus Immunoglobulin G (IgG)
Description
Antirotavirus immunoglobulin A (IgA) and IgG were measured by enzyme-linked immunosorbent assay at the Laboratory of Specialized Clinical Studies at the Cincinnati Children's Hospital Medical Center (Cincinnati, Ohio). A standard serum pool was used to determine arbitrary units of rotavirus IgA or IgG in each sample. A subject was considered seropositive if the IgA or IgG rotavirus antibody concentration was ≥20 U/mL.
Time Frame
8 weeks post vaccination
Title
Number/Percentage of Subjects Experiencing Immediate Post-vaccination Reactions Following Administration of Vaccine
Description
Immediate reactogenicity was defined as local or systemic reactions occurring directly and up to 30 minutes after vaccine receipt, with an emphasis on allergic reactions.
Time Frame
30 minutes post-vaccination
Title
Number/Percentage of Subjects Experiencing Solicited Adverse Events
Description
Solicited non-serious adverse events were collected based on recall at study visits 2 (Day 4) through 5 (Day 14) following administration of Rotarix® vaccine. They included diarrhea, fever, vomiting, loss of appetite, irritability, and intussusception. Adverse events were graded for severity and relationship to vaccine.
Time Frame
14 days post-vaccination
Title
Number/Percentage of Subjects Experiencing Unsolicited Non-serious Adverse Events
Description
Solicited non-serious adverse events were collected based on recall at study visits 2 (Day 4) through 5 (Day 14) following administration of Rotarix® vaccine. Adverse events were graded for severity and relationship to vaccine.
Time Frame
14 days post-vaccination
Title
Number/Percentage of Subjects Experiencing Serious Adverse Events
Description
An adverse event (AE) or suspected AE was considered "serious" if it resulted in any of the following outcomes:
Death
A life-threatening AE (the term "life-threatening" in the definition of "serious" refers to an event in which the patient was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe)
Inpatient hospitalization or prolongation of existing hospitalization
A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions
Important medical events that may not result in death, be life threatening, or require hospitalization would have been considered severe adverse events when, based upon appropriate medical judgment, they may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes listed in this definition.
Time Frame
2 months after vaccination
Other Pre-specified Outcome Measures:
Title
Geometric Mean Concentration (GMC) for Measles Virus Serum Neutralization Antibodies
Description
Sera were analyzed for the presence of measles virus serum neutralizing antibodies (SNAs), using a standardized plaque reduction neutralization (PRN) assay, in which PRN titers, defined as the serum dilutions that reduced the number of plaques by 50%, were calculated using the Kärber method [12]. A 1:100 dilution of World Health Organization (WHO) Second International Standard Anti-Measles Serum (IS, coded 66/202, supplied by the National Institute for Biological Standards and Control, South Mimms, United Kingdom) was tested in parallel with each serum specimen to calculate the reciprocal of the 50% end point titer determined by the PRN test.
Time Frame
8 weeks post vaccination
Title
Number of Participants With Rotavirus Vaccine Shedding
Description
Based on 5 grams of stool sample. Vaccine shedding defined as presence of vaccine-type rotavirus in stool at 4 (+/-1) and/or 7 (+/-1) days post rotavirus vaccination detected by enzyme-linked immunosorbent assay (ELISA) and typed by reverse-transcriptase polymerase chain reaction (RT-PCR).
Time Frame
Day 0, Day 4 and Day 7
10. Eligibility
Sex
All
Minimum Age & Unit of Time
9 Months
Maximum Age & Unit of Time
11 Months
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Child 9 months of age eligible for measles-rubella vaccination
documented evidence of a primary rotavirus vaccine series with first dose between 6 and 10 weeks of age and second dose at least 4 weeks after first dose
healthy infants free of chronic or serious medical condition as determined by history and physical examination at time of study enrollment
parents/guardians of each participant are able to understand and follow study procedures and agree to participate in study by providing signed informed consent
Exclusion Criteria:
hypersensitivity to any component of measles-rubella or Rotarix vaccine which would preclude administration of the vaccine
history of intussusception, intestinal malformations, or abdominal surgery
known history of measles and/or rubella disease
history of previous receipt of measles and/or rubella vaccine
use of any immunosuppressive drugs or immunoglobulin and/or blood products since birth or anticipated during study period
current enrolment in any other intervention trial or use of any investigational drug or vaccine throughout the study period
any participant who reports planning to leave the study area before the completion of the study
acute diarrhea (defined as ≥3 loose stools within a 24-hour period) or vomiting (defined as projectile vomiting or any vomiting at the discretion of the clinician) at the time of enrollment or within the last 24 hours
acute febrile illness (defined as a temperature of ≥38°C) at the time of enrollment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
K Zaman, PhD, MPH
Organizational Affiliation
International Centre for Diarrhoeal Disease Research, Bangladesh
Official's Role
Principal Investigator
Facility Information:
Facility Name
ICDDR,B
City
Dhaka
Country
Bangladesh
12. IPD Sharing Statement
Citations:
PubMed Identifier
26823338
Citation
Zaman K, Fleming JA, Victor JC, Yunus M, Bari TI, Azim T, Rahman M, Mowla SM, Bellini WJ, McNeal M, Icenogle JP, Lopman B, Parashar U, Cortese MM, Steele AD, Neuzil KM. Noninterference of Rotavirus Vaccine With Measles-Rubella Vaccine at 9 Months of Age and Improvements in Antirotavirus Immunity: A Randomized Trial. J Infect Dis. 2016 Jun 1;213(11):1686-93. doi: 10.1093/infdis/jiw024. Epub 2016 Jan 27.
Results Reference
derived
Learn more about this trial
Coadministration of Measles-rubella and Rotavirus Vaccines
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