Rotavirus InfectionPhase 4NCT02992197
The Effects of Increased Inoculum on Oral Rotavirus Vaccine Take and Immunogenicity
A Phase 4 study testing Rotarix, dose 1 and Rotarix, dose 2 in people with Rotavirus Infection and Vaccine Response Impaired, run by University of Vermont at 1 site in Bangladesh.
Trial summary
Rotavirus is the leading cause of diarrhea in children worldwide. Oral rotavirus vaccines work remarkably well in high-income countries, but for unclear reasons they underperform in low-income countries. Read more about this study
- Who is it for?
- Ages Up to 15 weeksHealthy volunteers can take part
- Conditions the study is for
- Rotavirus Infection, Vaccine Response Impaired, Vaccine Virus Shedding
- What is being tested?
- Rotarix, dose 1 and Rotarix, dose 2
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 220 participants
- Where
- 1 siteBangladesh
- Study dates
- 12 Jun 2017to 7 Jun 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 15 weeks
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Generally healthy infant (as determined by medical officers)
- Age 0-7 days at enrolment
- Mother willing and able to provide signed informed consent
- Mother willing to allow infant to be vaccinated according to study schedule
- Mother willing to allow biological specimens, including blood, stool, and saliva, to be collected from infant according to study protocol
- Mother willing and able to adhere to study schedule
Who cannot join
- Obvious congenital malformation
- Birth weight (if known) or enrolment weight (if birth weight unknown) < 2000 gm
- Known immunocompromising condition in infant
- Enrolment in other vaccine research trials
- Other household member enrolled in this study
Trial locations and contacts
1 site in 1 country.
Bangladesh1 site
International Center for Diarrhoeal Disease Research, Bangladesh (icddr,b)
Dhaka
About this study
Official title: A Double-blind, Randomized Controlled Trial of the Effect of Vaccine Inoculum on Oral Rotavirus Vaccine (Rotarix, GlaxoSmithKline) Take and Immunogenicity in Dhaka, Bangladesh
Rotavirus is the leading cause of diarrhea in children worldwide. Oral rotavirus vaccines work remarkably well in high-income countries, but for unclear reasons they underperform in low-income countries. A double-blind, randomized control trial will be performed to evaluate whether using a higher dose of a currently licensed vaccine (Rotarix, GlaxoSmithKline) can improve immune responses among infants in Dhaka, Bangladesh.
Infants will be randomized 1:1 to receive either a standard or a double dose of Rotarix at 6 and 10 weeks of life. Infants will be assessed for fecal vaccine shedding and serum rotavirus-specific IgA responses to determine vaccine immunogenicity.
- Being tested
- Rotarix, dose 1, Rotarix, dose 2, Placebo (for Rotarix dose 2)
- Keywords
- Rotavirus, Oral vaccines, Vaccine underperformance, Vaccine shedding
- Medical subject headings
- Rotavirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rotarix, dose 1Biological
Rotarix, dose 1
Rotarix, dose 2Biological
Rotarix, dose 2
Placebo (for Rotarix dose 2)Drug
Sterile water to provide volume equivalent as a second dose of Rotarix
| Study group | Role | What they receive |
|---|---|---|
| Rotarix, single dose | Active comparator | Rotarix 1.5 mL (standard single dose) and 1.5 mL of placebo by mouth (sterile, pharmacy-grade water) at both 6 and 10 weeks of life Receives: Biological: Rotarix, dose 1; Drug: Placebo (for Rotarix dose 2) |
| Rotarix, double dose | Experimental | Rotarix 3 mL by mouth (two standard doses administered simultaneously) at both 6 and 10 weeks of life Receives: Biological: Rotarix, dose 1; Biological: Rotarix, dose 2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number (or Percentage) of Infants in Each Study Arm Who Test Positive for Fecal Rotavirus Vaccine-strain Virus Shedding Post-vaccination
This will be an aggregate measure demonstrating a change from baseline. Infants will have stool collected immediately prior to Rotarix vaccination at weeks 6 and 10 of life, then 4, 7, and 14 days following each dose (i.e. last assessment at week 12 of life). Each specimen will be assessed for vaccine-strain virus (i.e. fecal vaccine shedding) at each time point by polymerase chain reaction. Any child who has a change in fecal vaccine shedding status, from negative at baseline (6 weeks) to positive at any subsequent time point, will be categorized as having met the outcome measure for positive fecal vaccine shedding.
Measured: Measured through week 12 of life
Number (or Percentage) of Infants in Each Study Arm With Rotavirus-specific Plasma Immunoglobulin A (IgA) Seroconversion Post-vaccination
This outcome will measure seroconversion, i.e. the change in plasma rotavirus-specific IgA concentration at week 14 of life compared to week 6 of life (baseline). Blood will be collected from infants prior to the first dose of Rotarix at week 6 of life and again at week 14 of life (4 weeks following the second dose) for measurement of plasma rotavirus-specific IgA by enzyme immunoassay. Infants will be assessed for seroconversion (IgA concentration <=20 U/mL pre-vaccination and >20 post-vaccination). Infants who demonstrate rotavirus-specific IgA seroconversion will be categorized as having met the outcome measure.
Measured: Measured at week 14 of life
Number (or Percentage) of Infants in Each Study Arm With Successful Vaccine Take, Defined as Positive Fecal Vaccine Shedding Post-vaccination OR Rotavirus-specific Plasma IgA Seroconversion Post-vaccination
Vaccine take is an aggregate, dichotomous immunogenicity measure (successful vaccine take vs no vaccine take). Infants positive for either fecal vaccine shedding OR plasma rotavirus-specific IgA seroconversion (as described in Outcomes 1 and 2, respectively) will be categorized as having met the outcome measure of successful vaccine take. Those who met neither outcome will be categorized as no vaccine take.
Measured: Measured at week 14 of life
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2016 (estimated)
- Study start12 Jun 2017
- Primary completion7 Jun 2018
- Study completion7 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rotavirus InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 220 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Vermont
- Sponsor type
- University, hospital or other
- Collaborators
- International Centre for Diarrhoeal Disease Research, Bangladesh, Charles H. Hood Foundation, Thrasher Research Fund
- Responsible party
- Principal investigator, Benjamin Lee, University of Vermont
- Investigators
- Benjamin Lee, M.D., Principal investigator, University of Vermont
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02992197
- Sponsor's protocol ID
- CHRMS 17-0166
- Status last verified
- Jul 2020
- First submitted
- 1 Dec 2016
- Last updated
- 4 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lee B, Dickson DM, Alam M, Afreen S, Kader A, Afrin F, Ferdousi T, Damon CF, Gullickson SK, McNeal MM, Bak DM, Tolba M, Carmolli MP, Taniuchi M, Haque R, Kirkpatrick BD. The effect of increased inoculum on oral rotavirus vaccine take among infants in Dhaka, Bangladesh: A double-blind, parallel group, randomized, controlled trial. Vaccine. 2020 Jan 3;38(1):90-99. doi: 10.1016/j.vaccine.2019.09.088. Epub 2019 Oct 10.
PubMed 31607603
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Randomized Controlled Trial of the Effect of Vaccine Inoculum on Oral Rotavirus Vaccine (Rotarix, GlaxoSmithKline) Take and Immunogenicity in Dhaka, Bangladesh
- ClinicalTrials.gov ID
- NCT02992197
- Acronym / sponsor ID
- CHRMS 17-0166
- Keywords
- Rotavirus, Oral vaccines, Vaccine underperformance, Vaccine shedding
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 220 participants (actual)
- Lead sponsor
- University of VermontUniversity, hospital or other
- Collaborators
- International Centre for Diarrhoeal Disease Research, Bangladesh, Charles H. Hood Foundation, Thrasher Research Fund
- Study start
- 12 Jun 2017 (actual)
- Primary completion
- 7 Jun 2018 (actual)
- Study completion
- 7 Jun 2018 (actual)
- First posted
- 14 Dec 2016 (estimated)
- Results
- Posted 17 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Rotavirus is the leading cause of diarrhea in children worldwide. Oral rotavirus vaccines work remarkably well in high-income countries, but for unclear reasons they underperform in low-income countries. A double-blind, randomized control trial will be performed to evaluate whether using a higher dose of a currently licensed vaccine (Rotarix, GlaxoSmithKline) can improve immune responses among infants in Dhaka, Bangladesh.
Infants will be randomized 1:1 to receive either a standard or a double dose of Rotarix at 6 and 10 weeks of life. Infants will be assessed for fecal vaccine shedding and serum rotavirus-specific IgA responses to determine vaccine immunogenicity.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rotarix, single dose | Active comparator | Biological: Rotarix, dose 1, Drug: Placebo (for Rotarix dose 2)Rotarix 1.5 mL (standard single dose) and 1.5 mL of placebo by mouth (sterile, pharmacy-grade water) at both 6 and 10 weeks of life |
| Rotarix, double dose | Experimental | Biological: Rotarix, dose 1, Biological: Rotarix, dose 2Rotarix 3 mL by mouth (two standard doses administered simultaneously) at both 6 and 10 weeks of life |
Who may qualify
- Ages
- Up to 15 weeks
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Generally healthy infant (as determined by medical officers)
- Age 0-7 days at enrolment
- Mother willing and able to provide signed informed consent
- Mother willing to allow infant to be vaccinated according to study schedule
- Mother willing to allow biological specimens, including blood, stool, and saliva, to be collected from infant according to study protocol
Key exclusion criteria (5 listed)
- Obvious congenital malformation
- Birth weight (if known) or enrolment weight (if birth weight unknown) < 2000 gm
- Known immunocompromising condition in infant
- Enrolment in other vaccine research trials
- Other household member enrolled in this study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rotarix, dose 1Rotarix, dose 1 | Biological | Rotarix, double dose, Rotarix, single dose |
| Rotarix, dose 2Rotarix, dose 2 | Biological | Rotarix, double dose |
| Placebo (for Rotarix dose 2)Sterile water to provide volume equivalent as a second dose of Rotarix | Drug | Rotarix, single dose |
Primary outcome
Number (or Percentage) of Infants in Each Study Arm Who Test Positive for Fecal Rotavirus Vaccine-strain Virus Shedding Post-vaccination
Time frame: Measured through week 12 of life
This will be an aggregate measure demonstrating a change from baseline. Infants will have stool collected immediately prior to Rotarix vaccination at weeks 6 and 10 of life, then 4, 7, and 14 days following each dose (i.e. last assessment at week 12 of life). Each specimen will be assessed for vaccine-strain virus (i.e. fecal vaccine shedding) at each time point by polymerase chain reaction. Any child who has a change in fecal vaccine shedding status, from negative at baseline (6 weeks) to positive at any subsequent time point, will be categorized as having met the outcome measure for positive fecal vaccine shedding.
Number (or Percentage) of Infants in Each Study Arm With Rotavirus-specific Plasma Immunoglobulin A (IgA) Seroconversion Post-vaccination
Time frame: Measured at week 14 of life
This outcome will measure seroconversion, i.e. the change in plasma rotavirus-specific IgA concentration at week 14 of life compared to week 6 of life (baseline). Blood will be collected from infants prior to the first dose of Rotarix at week 6 of life and again at week 14 of life (4 weeks following the second dose) for measurement of plasma rotavirus-specific IgA by enzyme immunoassay. Infants will be assessed for seroconversion (IgA concentration <=20 U/mL pre-vaccination and >20 post-vaccination). Infants who demonstrate rotavirus-specific IgA seroconversion will be categorized as having met the outcome measure.
Number (or Percentage) of Infants in Each Study Arm With Successful Vaccine Take, Defined as Positive Fecal Vaccine Shedding Post-vaccination OR Rotavirus-specific Plasma IgA Seroconversion Post-vaccination
Time frame: Measured at week 14 of life
Vaccine take is an aggregate, dichotomous immunogenicity measure (successful vaccine take vs no vaccine take). Infants positive for either fecal vaccine shedding OR plasma rotavirus-specific IgA seroconversion (as described in Outcomes 1 and 2, respectively) will be categorized as having met the outcome measure of successful vaccine take. Those who met neither outcome will be categorized as no vaccine take.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31607603Lee B, Dickson DM, Alam M, Afreen S, Kader A, Afrin F, Ferdousi T, Damon CF, Gullickson SK, McNeal MM, Bak DM, Tolba M, Carmolli MP, Taniuchi M, Haque R, Kirkpatrick BD. The effect of increased inoculum on oral rotavirus vaccine take among infants in Dhaka, Bangladesh: A double-blind, parallel group, randomized, controlled trial. Vaccine. 2020 Jan 3;38(1):90-99. doi: 10.1016/j.vaccine.2019.09.088. Epub 2019 Oct 10.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Benjamin Lee, M.D. principal investigator
University of Vermont
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Rotarix, dose 1 and Rotarix, dose 2 in people with Rotavirus Infection and Vaccine Response Impaired, run by University of Vermont at 1 site in Bangladesh.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Bangladesh. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number (or Percentage) of Infants in Each Study Arm Who Test Positive for Fecal Rotavirus Vaccine-strain Virus Shedding Post-vaccination (time frame: Measured through week 12 of life). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02992197, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2020.