Coadministration of Measles-rubella and Rotavirus Vaccines
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: measles-rubella and rotavirus vaccines 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 |
Biological: Rotarix vaccine
one 1.0 ml dose of oral rotavirus vaccine at 9 months of age
Other Names:
Biological: measles-rubella vaccine
one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine
Other Names:
|
| Active Comparator: measles-rubella vaccine receive one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine at 9 months of age |
Biological: measles-rubella vaccine
one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percentage/Number of Subjects With Seroprotection for Measles Virus Serum Neutralization Antibodies [8 weeks post vaccination]
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) [8 weeks post vaccination]
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) [8 weeks post vaccination]
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) [8 weeks post vaccination]
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) [Visit 1 (pre-vaccination) and 8 weeks post vaccination]
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) [Visit 1 (pre-vaccination) and 8 weeks post vaccination]
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) [Visit 1 (pre-vaccination) and 8 weeks post vaccination]
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) [Visit 1 (pre-vaccination) and 8 weeks post vaccination]
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) [8 weeks post vaccination]
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) [8 weeks post vaccination]
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 [30 minutes post-vaccination]
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 [14 days post-vaccination]
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 [14 days post-vaccination]
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 [2 months after vaccination]
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.
Other Outcome Measures
- Geometric Mean Concentration (GMC) for Measles Virus Serum Neutralization Antibodies [8 weeks post vaccination]
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.
- Number of Participants With Rotavirus Vaccine Shedding [Day 0, Day 4 and Day 7]
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).
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | ICDDR,B | Dhaka | Bangladesh |
Sponsors and Collaborators
- PATH
Investigators
- Principal Investigator: K Zaman, PhD, MPH, International Centre for Diarrhoeal Disease Research, Bangladesh
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HS677
Study Results
Participant Flow
| Recruitment Details | Study population was drawn from participants living in the International Center for Diarrheal Disease Research, Bangladesh (icddr,b) service area of Matlab, Bangladesh. |
|---|---|
| Pre-assignment Detail | Recruitment concurrently conducted at a number of health sites in the study area, which resulted in two additional infants being enrolled but subsequently not vaccinated with withdrawn from the study. |
| Arm/Group Title | Measles-rubella and Rotavirus Vaccines | Measles-rubella Vaccine |
|---|---|---|
| Arm/Group 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 Rotarix vaccine: one 1.0 ml dose of oral rotavirus vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine | receive one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine |
| Period Title: Received Study Vaccines | ||
| STARTED | 240 | 240 |
| COMPLETED | 240 | 240 |
| NOT COMPLETED | 0 | 0 |
| Period Title: Received Study Vaccines | ||
| STARTED | 240 | 240 |
| COMPLETED | 227 | 233 |
| NOT COMPLETED | 13 | 7 |
Baseline Characteristics
| Arm/Group Title | Measles-rubella and Rotavirus Vaccines | Measles-rubella Vaccine | Total |
|---|---|---|---|
| Arm/Group 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 Rotarix vaccine: one 1.0 ml dose of oral rotavirus vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine | receive one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine | Total of all reporting groups |
| Overall Participants | 240 | 240 | 480 |
| Age (months) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [months] |
9.38
(0.252)
|
9.39
(0.254)
|
9.38
(0.253)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
110
45.8%
|
123
51.3%
|
233
48.5%
|
| Male |
130
54.2%
|
117
48.8%
|
247
51.5%
|
| Currently breastfed (Count of Participants) | |||
| Yes |
236
98.3%
|
238
99.2%
|
474
98.8%
|
| No |
4
1.7%
|
2
0.8%
|
6
1.3%
|
| Length (cm) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [cm] |
69.56
(2.488)
|
69.81
(2.786)
|
69.68
(2.642)
|
| Weight (kilograms) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [kilograms] |
8.01
(1.101)
|
7.97
(0.933)
|
7.99
(1.047)
|
| Mother's age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
27.1
(5.84)
|
26.7
(5.90)
|
26.9
(5.87)
|
Outcome Measures
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Measles-rubella and Rotavirus Vaccines | Measles-rubella Vaccine |
|---|---|---|
| Arm/Group 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 Rotarix vaccine: one 1.0 ml dose of oral rotavirus vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine | receive one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine |
| Measure Participants | 227 | 233 |
| Seroprotection |
171
71.3%
|
173
72.1%
|
| No seroprotection |
56
23.3%
|
60
25%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Measles-rubella and Rotavirus Vaccines, Measles-rubella Vaccine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority | |
| Comments | A noninferiority margin of -10% was chosen as the maximal absolute reduction in proportion seroprotection allowed in the concomitant measles-rubella and rotavirus vaccine group as compared to the measles-rubella vaccine alone group. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Seroconversion proportion difference |
| Estimated Value | 1.1 | |
| Confidence Interval |
(2-Sided) 95% -6.9 to 9.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All children meeting inclusion/exclusion criteria with a valid sample. |
| Arm/Group Title | Measles-rubella and Rotavirus Vaccines | Measles-rubella Vaccine |
|---|---|---|
| Arm/Group 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 Rotarix vaccine: one 1.0 ml dose of oral rotavirus vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine | receive one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine |
| Measure Participants | 227 | 232 |
| Seroprotection |
219
91.3%
|
227
94.6%
|
| No seroprotection |
8
3.3%
|
5
2.1%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All children meeting inclusion and exclusion criteria with valid samples. |
| Arm/Group Title | Measles-rubella and Rotavirus Vaccines | Measles-rubella Vaccine |
|---|---|---|
| Arm/Group 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 Rotarix vaccine: one 1.0 ml dose of oral rotavirus vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine | receive one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine |
| Measure Participants | 228 | 234 |
| Seroprotection |
228
95%
|
233
97.1%
|
| No seroprotection |
0
0%
|
1
0.4%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Measles-rubella and Rotavirus Vaccines | Measles-rubella Vaccine |
|---|---|---|
| Arm/Group 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 Rotarix vaccine: one 1.0 ml dose of oral rotavirus vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine | receive one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine |
| Measure Participants | 228 | 234 |
| Geometric Mean (95% Confidence Interval) [IU/mL] |
191.9
|
177.8
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants meeting inclusion/exclusion criteria and with valid samples. |
| Arm/Group Title | Measles-rubella and Rotavirus Vaccine | Measles-rubella Vaccine |
|---|---|---|
| Arm/Group 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 Rotarix vaccine: one 1.0 ml dose of oral rotavirus vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine | receive one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine |
| Measure Participants | 239 | 240 |
| Seropositive |
126
52.5%
|
113
47.1%
|
| Not seropositive |
113
47.1%
|
127
52.9%
|
| Seropositive |
160
66.7%
|
110
45.8%
|
| Not seropositive |
70
29.2%
|
130
54.2%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants meeting inclusion/exclusion criteria and with valid samples. |
| Arm/Group Title | Measles-rubella and Rotavirus Vaccines | Measles-rubella Vaccine |
|---|---|---|
| Arm/Group 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 Rotarix vaccine: one 1.0 ml dose of oral rotavirus vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine | receive one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine |
| Measure Participants | 239 | 240 |
| Pre-vaccination |
43.6
|
39.2
|
| Post-vaccination |
60.6
|
38.1
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants meeting inclusion/exclusion criteria and with valid samples. |
| Arm/Group Title | Measles-rubella and Rotavirus Vaccines | Measles-rubella Vaccine |
|---|---|---|
| Arm/Group 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 Rotarix vaccine: one 1.0 ml dose of oral rotavirus vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine | receive one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine |
| Measure Participants | 240 | 240 |
| Seropositive |
159
66.3%
|
140
58.3%
|
| Not seropositive |
81
33.8%
|
100
41.7%
|
| Seropositive |
204
85%
|
135
56.3%
|
| Not seropositive |
27
11.3%
|
101
42.1%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants meeting inclusion/exclusion criteria and with valid samples. |
| Arm/Group Title | Measles-rubella and Rotavirus Vaccines | Measles-rubella Vaccine |
|---|---|---|
| Arm/Group 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 Rotarix vaccine: one 1.0 ml dose of oral rotavirus vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine | receive one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine |
| Measure Participants | 240 | 240 |
| Pre-vaccination |
79.2
|
63.2
|
| Post-vaccination |
168.6
|
60.1
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All subjects that met inclusion and exclusion criteria with valid samples and were not seropositive prior to the intervention |
| Arm/Group Title | Measles-rubella and Rotavirus Vaccines | Measles-rubella Vaccine |
|---|---|---|
| Arm/Group 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 Rotarix vaccine: one 1.0 ml dose of oral rotavirus vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine | receive one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine |
| Measure Participants | 110 | 126 |
| Seroconversion |
48
20%
|
8
3.3%
|
| No seroconversion |
62
25.8%
|
118
49.2%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Measles-rubella and Rotavirus Vaccines | Measles-rubella Vaccine |
|---|---|---|
| Arm/Group 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 Rotarix vaccine: one 1.0 ml dose of oral rotavirus vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine | receive one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine |
| Measure Participants | 80 | 99 |
| Seroconversion |
55
22.9%
|
7
2.9%
|
| No seroconversion |
25
10.4%
|
92
38.3%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Measles-rubella and Rotavirus Vaccines | Measles-rubella Vaccine |
|---|---|---|
| Arm/Group 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 Rotarix vaccine: one 1.0 ml dose of oral rotavirus vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine | receive one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine |
| Measure Participants | 240 | 240 |
| Any immediate reaction |
0
0%
|
0
0%
|
| No immediate reaction |
240
100%
|
240
100%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Measles-rubella and Rotavirus Vaccines | Measles-rubella Vaccine |
|---|---|---|
| Arm/Group 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 Rotarix vaccine: one 1.0 ml dose of oral rotavirus vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine | receive one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine |
| Measure Participants | 240 | 240 |
| Grade 1: unrelated to vaccine |
25
10.4%
|
34
14.2%
|
| Grade 2: unrelated to vaccine |
4
1.7%
|
4
1.7%
|
| Grade 3: unrelated to vaccine |
2
0.8%
|
0
0%
|
| None |
209
87.1%
|
202
84.2%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Measles-rubella and Rotavirus Vaccines | Measles-rubella Vaccine |
|---|---|---|
| Arm/Group 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 Rotarix vaccine: one 1.0 ml dose of oral rotavirus vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine | receive one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine |
| Measure Participants | 240 | 240 |
| Related to vaccine |
0
0%
|
0
0%
|
| Unrelated to vaccine |
63
26.3%
|
68
28.3%
|
| No unsolicited non-serious adverse event |
177
73.8%
|
172
71.7%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Measles-rubella and Rotavirus Vaccines | Measles-rubella Vaccine |
|---|---|---|
| Arm/Group 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 Rotarix vaccine: one 1.0 ml dose of oral rotavirus vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine | receive one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine |
| Measure Participants | 240 | 240 |
| Any serious adverse event, unrelated to vaccine |
10
4.2%
|
6
2.5%
|
| No serious adverse event |
230
95.8%
|
234
97.5%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Measles-rubella and Rotavirus Vaccines | Measles-rubella Vaccine |
|---|---|---|
| Arm/Group 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 Rotarix vaccine: one 1.0 ml dose of oral rotavirus vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine | receive one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine |
| Measure Participants | 227 | 233 |
| Geometric Mean (95% Confidence Interval) [mIU/mL] |
196.3
|
194.2
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Measles-rubella and Rotavirus Vaccines |
|---|---|
| Arm/Group 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 Rotarix vaccine: one 1.0 ml dose of oral rotavirus vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine |
| Measure Participants | 240 |
| Negative |
140
58.3%
|
| Positive |
0
0%
|
| No stool |
100
41.7%
|
| Negative |
234
97.5%
|
| Positive |
4
1.7%
|
| No stool |
2
0.8%
|
| Negative |
234
97.5%
|
| Positive |
6
2.5%
|
| No stool |
0
0%
|
Adverse Events
| Time Frame | 2 months after vaccination | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Local and systemic adverse events were assessed on days 4, 7, 11, 14, and 28 after vaccination through home visits by trained field workers. Solicited adverse events includes diarrhea, fever, vomiting, loss of appetite, irritability, and signs of intussusception (colicky abdominal pain or paroxysms of crying/screaming, abdominal distension or mass, intermittent irritability or lethargy with behavioral changes, stool with blood or "red currant jelly," and/or vomiting ≥2 episodes/day). | |||
| Arm/Group Title | Measles-rubella and Rotavirus Vaccines | Measles-rubella Vaccine | ||
| Arm/Group 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 Rotarix vaccine: one 1.0 ml dose of oral rotavirus vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine | receive one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine at 9 months of age measles-rubella vaccine: one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine | ||
All Cause Mortality |
||||
| Measles-rubella and Rotavirus Vaccines | Measles-rubella Vaccine | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/240 (0%) | 0/240 (0%) | ||
Serious Adverse Events |
||||
| Measles-rubella and Rotavirus Vaccines | Measles-rubella Vaccine | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 10/240 (4.2%) | 6/240 (2.5%) | ||
| Gastrointestinal disorders | ||||
| Acute watery diarrhea | 4/240 (1.7%) | 4 | 3/240 (1.3%) | 3 |
| Infections and infestations | ||||
| Acute bronchiolitis | 1/240 (0.4%) | 1 | 1/240 (0.4%) | 1 |
| Pneumonia | 1/240 (0.4%) | 1 | 0/240 (0%) | 0 |
| Pneumonia with UTI | 1/240 (0.4%) | 1 | 0/240 (0%) | 0 |
| Urinary tract infection | 2/240 (0.8%) | 2 | 0/240 (0%) | 0 |
| Severe pneumonia | 0/240 (0%) | 0 | 1/240 (0.4%) | 1 |
| Nervous system disorders | ||||
| Febrile convulsion | 0/240 (0%) | 0 | 1/240 (0.4%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute nasopharyngitis | 1/240 (0.4%) | 1 | 0/240 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Measles-rubella and Rotavirus Vaccines | Measles-rubella Vaccine | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 63/240 (26.3%) | 68/240 (28.3%) | ||
| Ear and labyrinth disorders | ||||
| Ear pain | 1/240 (0.4%) | 0/240 (0%) | ||
| Gastrointestinal disorders | ||||
| Abdominal distension | 0/240 (0%) | 1/240 (0.4%) | ||
| Dysentery | 9/240 (3.8%) | 12/240 (5%) | ||
| Mouth ulceration | 1/240 (0.4%) | 0/240 (0%) | ||
| Oral candidiasis | 1/240 (0.4%) | 0/240 (0%) | ||
| Infections and infestations | ||||
| Conjunctivitis | 0/240 (0%) | 1/240 (0.4%) | ||
| Fungal infection | 2/240 (0.8%) | 1/240 (0.4%) | ||
| Otitis media chronic | 3/240 (1.3%) | 0/240 (0%) | ||
| Pneumonia | 1/240 (0.4%) | 1/240 (0.4%) | ||
| Respiratory tract infection | 16/240 (6.7%) | 13/240 (5.4%) | ||
| Urinary tract infection | 1/240 (0.4%) | 0/240 (0%) | ||
| Varicella | 0/240 (0%) | 1/240 (0.4%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 5/240 (2.1%) | 4/240 (1.7%) | ||
| Nasopharyngitis | 32/240 (13.3%) | 38/240 (15.8%) | ||
| Respiratory distress | 1/240 (0.4%) | 0/240 (0%) | ||
| Rhinorrhoea | 1/240 (0.4%) | 0/240 (0%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Jorge Flores |
|---|---|
| Organization | PATH |
| Phone | (202) 822-0033 |
| jeflores@path.org |
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