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| Name | Class |
|---|---|
| Bill and Melinda Gates Foundation | OTHER |
| University of Virginia | OTHER |
| International Centre for Diarrhoeal Disease Research, Bangladesh | OTHER |
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Oral polio and rotavirus vaccines are significantly less effective in children living in the developing world. Tropical enteropathy, which is associated with intestinal inflammation, decreased absorption and increased permeability, may contribute substantially to oral vaccine failure in developing country settings. Other possible causes of oral vaccine underperformance include malnutrition, interference with maternal or breastmilk antibodies, changes in gut microbiota, and genetic susceptibility.
Primary Objective: to determine whether tropical enteropathy impairs the efficacy of oral polio and rotavirus vaccines in children in Bangladesh.
Secondary Objectives: 1) to determine the impact of an IPV (inactivated polio vaccine) boost on the efficacy of OPV (oral polio vaccine) and 2) to determine the efficacy of Rotarix oral rotavirus vaccine to prevent rotavirus diarrhea
The polio and rotavirus randomized clinical trials are embedded as secondary objectives within the exploratory study of tropical enteropathy. The primary and secondary outcome measures are relevant to the randomized clinical trials.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Rotarix + No IPV (inactivated polio vaccine) | Experimental | Oral Rotarix vaccine at 10 and 17 weeks of age and oral polio vaccine series |
|
| Rotarix + IPV (inactivated polio vaccine) | Experimental | Oral Rotarix vaccine at 10 and 17 weeks of age plus IPV (inactivated polio vaccine) boost in place of oral polio vaccine dose at 39 weeks |
|
| No Rotarix + No IPV (inactivated polio vaccine) | No Intervention | No Rotarix and oral polio vaccine series only | |
| No Rotarix + IPV (inactivated polio vaccine) | Experimental | No Rotarix vaccine and IPV (inactivated polio vaccine) boost in place of oral polio vaccine dose at 39 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IPV (inactivated polio vaccine) | Biological | Administered per protocol |
|
| Measure | Description | Time Frame |
|---|---|---|
| Presence of Fecal Shedding of Polio Vaccine Virus Determined by Culture (Polio Trial) | Any Sabin type poliovirus in any fecal samples at days 0, 4, 11, 18 or 25 following week 52 dose | 25 days following week 52 visit |
| Number of Participants With One or More Episodes of Rotavirus-associated Diarrhea (Rotavirus Trial) | Diarrheal episode defined as presence of 3 or more abnormally loose stools in 24h period with >=72 hours separating episodes. Rotavirus antigen detected by ELISA in diarrheal stool. | Birth to one year |
| Measure | Description | Time Frame |
|---|---|---|
| Duration of Fecal Shedding of Polio Vaccine Virus, Each Sabin Type (Polio Trial) | Shedding index, calculated as duration days multiplied by mean log (shedding amount) for Sabin types 1, 2, and 3. Outcome is conditioned on infants with at least one detection by quantitative PCR (qPCR) at day 4,11,18, or 25. If shedding data point was missing it was assumed that the infant was not shedding at that time. Lower shedding index is better outcome |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Beth Kirkpatrick, M.D. | University of Vermont | Principal Investigator |
| William Petri, M.D., Ph.D. | University of Virginia School of Medicine | Principal Investigator |
| Rashidul Haque, M.D., Ph.D. | International Center for Diarrhoeal Disease Research, Bangladesh | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| International Centre for Diarrhoeal Disease Research, Bangladesh | Dhaka | Bangladesh |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25711607 | Background | Kirkpatrick BD, Colgate ER, Mychaleckyj JC, Haque R, Dickson DM, Carmolli MP, Nayak U, Taniuchi M, Naylor C, Qadri F, Ma JZ, Alam M, Walsh MC, Diehl SA; PROVIDE Study Teams; Petri WA Jr. The "Performance of Rotavirus and Oral Polio Vaccines in Developing Countries" (PROVIDE) study: description of methods of an interventional study designed to explore complex biologic problems. Am J Trop Med Hyg. 2015 Apr;92(4):744-51. doi: 10.4269/ajtmh.14-0518. Epub 2015 Feb 23. | |
| 27217217 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Rotarix + IPV (Inactivated Polio Vaccine) | Rotarix vaccine at 10 and 17 weeks of age plus IPV (inactivated polio vaccine) boost at 39 weeks in place of routine oral polio vaccine dose |
| FG001 | Rotarix + No IPV (Inactivated Polio Vaccine) | Rotarix vaccine at 10 and 17 weeks of age and routine oral polio vaccine series |
| FG002 | No Rotarix + IPV (Inactivated Polio Vaccine) | IPV (inactivated polio vaccine) boost at 39 weeks in place of routine oral polio vaccine dose |
| FG003 | No Rotarix + No IPV (Inactivated Polio Vaccine) | No Rotarix vaccine and routine oral polio vaccine series |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Rotarix + IPV (Inactivated Polio Vaccine) | Rotarix vaccine at 10 and 17 weeks of age plus IPV (inactivated polio vaccine) boost in place of the routine oral polio vaccine dose at 39 weeks |
| BG001 | Rotarix + No IPV (Inactivated Polio Vaccine) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Presence of Fecal Shedding of Polio Vaccine Virus Determined by Culture (Polio Trial) | Any Sabin type poliovirus in any fecal samples at days 0, 4, 11, 18 or 25 following week 52 dose | Intention to treat. All participants analyzed as randomized | Posted | Count of Participants | Participants | 25 days following week 52 visit |
|
Birth to one year
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Rotarix + IPV | Rotarix vaccine at 10 and 17 weeks of age plus inactivated polio vaccine in place of the routine oral polio vaccine dose at 39 weeks |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dorothy M Dickson, MSc | University of Vermont | 802 656 9296 | dorothy.dickson@med.uvm.edu |
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| ID | Term |
|---|---|
| D013182 | Sprue, Tropical |
| ID | Term |
|---|---|
| D008286 | Malabsorption Syndromes |
| D007410 | Intestinal Diseases |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D011054 | Poliovirus Vaccine, Inactivated |
| C492457 | RIX4414 vaccine |
| ID | Term |
|---|---|
| D015164 | Vaccines, Inactivated |
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
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| Washington University School of Medicine |
| OTHER |
| Stanford University | OTHER |
| Centers for Disease Control and Prevention | FED |
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| Rotarix | Biological | Administered per protocol |
|
| from day 4 to day 25 following the week 52 visit |
| Community Fecal Shedding of Polio Vaccine Virus Just Prior to Oral Polio Vaccine Dose at 52 Weeks (Polio Trial) | Only 8 infants were shedding at baseline so results are not presented for this outcome due to insufficient data | post 52 weeks |
| Presence of Fecal Polio Virus Shedding Within the Three Sabin Strains (Polio Trial) | Frequency (%) of infants excreting poliovirus at any of the 5 time points (day 0, 4,11,18, 25) post week 52 oral polio vaccine dose. Presence of poliovirus is determined by polymerase chain reaction (PCR) | 25 days following week 52 visit |
| Serum Neutralizing Antibody Response (Polio Trial) | Seropositive defined as antibodies present at ≥1:8 dilution, antibody titers <1:8 were seronegative. Non-seroconversions are those who did not seroconvert between week 18 (post oral polio vaccine dose 2) and week 40, adjusted for residual maternal antibody | 18-40 weeks |
| Total Number of Diarrheal Episodes (Rotavirus Trial) | A diarrheal episode is defined as the presence of 3 or more abnormally loose stools in a 24 hour period with at least 72 diarrhea-free hours separating distinct episodes | Birth to one year |
| Total Duration of Rotavirus-associated Diarrheal Episodes (Rotavirus Trial) | A diarrheal episode is defined as the presence of 3 or more abnormally loose stools in a 24 hour period with at least 72 diarrhea-free hours separating distinct episodes. Rotavirus positive specimens were determined by ELISA Those with no rotavirus diarrheal episodes are counted as duration 0 | Birth to one year |
| Result |
| Colgate ER, Haque R, Dickson DM, Carmolli MP, Mychaleckyj JC, Nayak U, Qadri F, Alam M, Walsh MC, Diehl SA, Zaman K, Petri WA, Kirkpatrick BD. Delayed Dosing of Oral Rotavirus Vaccine Demonstrates Decreased Risk of Rotavirus Gastroenteritis Associated With Serum Zinc: A Randomized Controlled Trial. Clin Infect Dis. 2016 Sep 1;63(5):634-41. doi: 10.1093/cid/ciw346. Epub 2016 May 23. |
| 26643930 | Result | Mychaleckyj JC, Haque R, Carmolli M, Zhang D, Colgate ER, Nayak U, Taniuchi M, Dickson D, Weldon WC, Oberste MS, Zaman K, Houpt ER, Alam M, Kirkpatrick BD, Petri WA Jr. Effect of substituting IPV for tOPV on immunity to poliovirus in Bangladeshi infants: An open-label randomized controlled trial. Vaccine. 2016 Jan 12;34(3):358-66. doi: 10.1016/j.vaccine.2015.11.046. Epub 2015 Nov 28. |
| 26870801 | Result | Naylor C, Lu M, Haque R, Mondal D, Buonomo E, Nayak U, Mychaleckyj JC, Kirkpatrick B, Colgate R, Carmolli M, Dickson D, van der Klis F, Weldon W, Steven Oberste M; PROVIDE study teams; Ma JZ, Petri WA Jr. Environmental Enteropathy, Oral Vaccine Failure and Growth Faltering in Infants in Bangladesh. EBioMedicine. 2015 Sep 25;2(11):1759-66. doi: 10.1016/j.ebiom.2015.09.036. eCollection 2015 Nov. |
| 39052701 | Derived | Ciszewski J, Taniuchi M, Lee B, Colgate ER, Platts-Mills JA, Haque R, Zaman K, Lopman B, Petri WA Jr, Kirkpatrick BD, Rogawski McQuade ET. Differences in Rotavirus Shedding and Duration by Infant Oral Rotavirus Vaccination Status in Dhaka, Bangladesh, 2011-2014. J Infect Dis. 2024 Jul 25;230(1):e75-e79. doi: 10.1093/infdis/jiad502. |
| 34565452 | Derived | Kupkova K, Shetty SJ, Haque R, Petri WA Jr, Auble DT. Histone H3 lysine 27 acetylation profile undergoes two global shifts in undernourished children and suggests altered one-carbon metabolism. Clin Epigenetics. 2021 Sep 26;13(1):182. doi: 10.1186/s13148-021-01173-8. |
| 32867719 | Derived | Lin Y, Zhou J, Kumar S, Xie W, G Jensen SK, Haque R, Nelson CA, Petri WA Jr, Ma JZ. Group penalized generalized estimating equation for correlated event-related potentials and biomarker selection. BMC Med Res Methodol. 2020 Aug 31;20(1):221. doi: 10.1186/s12874-020-01103-x. |
| 32157282 | Derived | Williams FB, Kader A, Colgate ER, Dickson DM, Carmolli M, Uddin MI, Sharmin S, Islam S, Bhuiyan TR, Alam M, Nayak U, Mychaleckyj JC, Petri WA, Haque R, Qadri F, Kirkpatrick BD, Lee B. Maternal Secretor Status Affects Oral Rotavirus Vaccine Response in Breastfed Infants in Bangladesh. J Infect Dis. 2021 Oct 13;224(7):1147-1151. doi: 10.1093/infdis/jiaa101. |
| 29514306 | Derived | Rogawski ET, Platts-Mills JA, Colgate ER, Haque R, Zaman K, Petri WA, Kirkpatrick BD. Quantifying the Impact of Natural Immunity on Rotavirus Vaccine Efficacy Estimates: A Clinical Trial in Dhaka, Bangladesh (PROVIDE) and a Simulation Study. J Infect Dis. 2018 Mar 5;217(6):861-868. doi: 10.1093/infdis/jix668. |
| 29394355 | Derived | Lee B, Carmolli M, Dickson DM, Colgate ER, Diehl SA, Uddin MI, Islam S, Hossain M, Rafique TA, Bhuiyan TR, Alam M, Nayak U, Mychaleckyj JC, McNeal MM, Petri WA, Qadri F, Haque R, Kirkpatrick BD. Rotavirus-Specific Immunoglobulin A Responses Are Impaired and Serve as a Suboptimal Correlate of Protection Among Infants in Bangladesh. Clin Infect Dis. 2018 Jul 2;67(2):186-192. doi: 10.1093/cid/ciy076. |
| 29390150 | Derived | Lee B, Dickson DM, deCamp AC, Ross Colgate E, Diehl SA, Uddin MI, Sharmin S, Islam S, Bhuiyan TR, Alam M, Nayak U, Mychaleckyj JC, Taniuchi M, Petri WA Jr, Haque R, Qadri F, Kirkpatrick BD. Histo-Blood Group Antigen Phenotype Determines Susceptibility to Genotype-Specific Rotavirus Infections and Impacts Measures of Rotavirus Vaccine Efficacy. J Infect Dis. 2018 Apr 11;217(9):1399-1407. doi: 10.1093/infdis/jiy054. |
| 28444240 | Derived | Upfill-Brown A, Taniuchi M, Platts-Mills JA, Kirkpatrick B, Burgess SL, Oberste MS, Weldon W, Houpt E, Haque R, Zaman K, Petri WA Jr. Nonspecific Effects of Oral Polio Vaccine on Diarrheal Burden and Etiology Among Bangladeshi Infants. Clin Infect Dis. 2017 Aug 1;65(3):414-419. doi: 10.1093/cid/cix354. |
| 28293424 | Derived | Lu M, Zhou J, Naylor C, Kirkpatrick BD, Haque R, Petri WA Jr, Ma JZ. Application of penalized linear regression methods to the selection of environmental enteropathy biomarkers. Biomark Res. 2017 Mar 9;5:9. doi: 10.1186/s40364-017-0089-4. eCollection 2017. |
| 27154394 | Derived | Taniuchi M, Platts-Mills JA, Begum S, Uddin MJ, Sobuz SU, Liu J, Kirkpatrick BD, Colgate ER, Carmolli MP, Dickson DM, Nayak U, Haque R, Petri WA Jr, Houpt ER. Impact of enterovirus and other enteric pathogens on oral polio and rotavirus vaccine performance in Bangladeshi infants. Vaccine. 2016 Jun 8;34(27):3068-3075. doi: 10.1016/j.vaccine.2016.04.080. Epub 2016 May 3. |
| Death |
|
| Withdrawal by Subject |
|
| Physician Decision |
|
Oral Rotarix vaccine at 10 and 17 weeks of age and regular routine oral polio vaccine series |
| BG002 | No Rotarix + IPV (Inactivated Polio Vaccine) | No Rotarix vaccine and IPV (inactivated polio vaccine) boost in place of the routine oral polio vaccine dose at 39 weeks |
| BG003 | No Rotarix + No IPV (Inactivated Polio Vaccine) | No Rotarix vaccine and routine oral polio vaccine series |
| BG004 | Total | Total of all reporting groups |
| days |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
|
| Primary | Number of Participants With One or More Episodes of Rotavirus-associated Diarrhea (Rotavirus Trial) | Diarrheal episode defined as presence of 3 or more abnormally loose stools in 24h period with >=72 hours separating episodes. Rotavirus antigen detected by ELISA in diarrheal stool. | Intention to treat. All randomized participants are analyzed in the arms to which they were randomized. | Posted | Count of Participants | Participants | Birth to one year |
|
|
|
|
| Secondary | Duration of Fecal Shedding of Polio Vaccine Virus, Each Sabin Type (Polio Trial) | Shedding index, calculated as duration days multiplied by mean log (shedding amount) for Sabin types 1, 2, and 3. Outcome is conditioned on infants with at least one detection by quantitative PCR (qPCR) at day 4,11,18, or 25. If shedding data point was missing it was assumed that the infant was not shedding at that time. Lower shedding index is better outcome | This differs from the total population because it is a subset of total participants, limited to only those who shed the virus as determined by quantitative PCR assay (qPCR) Number analyzed differs from the number of participants shedding in outcome 5 (Presence of fecal polio virus shedding) because this shedding subset is determined using a different assay and time frame | Posted | Mean | Standard Deviation | units on a scale | from day 4 to day 25 following the week 52 visit |
|
|
|
|
| Secondary | Community Fecal Shedding of Polio Vaccine Virus Just Prior to Oral Polio Vaccine Dose at 52 Weeks (Polio Trial) | Only 8 infants were shedding at baseline so results are not presented for this outcome due to insufficient data | Not Posted | post 52 weeks | Participants |
| Secondary | Presence of Fecal Polio Virus Shedding Within the Three Sabin Strains (Polio Trial) | Frequency (%) of infants excreting poliovirus at any of the 5 time points (day 0, 4,11,18, 25) post week 52 oral polio vaccine dose. Presence of poliovirus is determined by polymerase chain reaction (PCR) | Total Intention to treat population, all participants are included as randomized Number shedding differs from the number analyzed in outcome 3 (Duration of fecal shedding of polio vaccine virus) because shedding detection here is based on positive/negative PCR assay result | Posted | Count of Participants | Participants | 25 days following week 52 visit |
|
|
|
|
| Secondary | Serum Neutralizing Antibody Response (Polio Trial) | Seropositive defined as antibodies present at ≥1:8 dilution, antibody titers <1:8 were seronegative. Non-seroconversions are those who did not seroconvert between week 18 (post oral polio vaccine dose 2) and week 40, adjusted for residual maternal antibody | Intention to treat | Posted | Count of Participants | Participants | 18-40 weeks |
|
|
|
|
| Secondary | Total Number of Diarrheal Episodes (Rotavirus Trial) | A diarrheal episode is defined as the presence of 3 or more abnormally loose stools in a 24 hour period with at least 72 diarrhea-free hours separating distinct episodes | Intention to treat population, included as randomized | Posted | Median | Inter-Quartile Range | episodes | Birth to one year |
|
|
|
|
| Secondary | Total Duration of Rotavirus-associated Diarrheal Episodes (Rotavirus Trial) | A diarrheal episode is defined as the presence of 3 or more abnormally loose stools in a 24 hour period with at least 72 diarrhea-free hours separating distinct episodes. Rotavirus positive specimens were determined by ELISA Those with no rotavirus diarrheal episodes are counted as duration 0 | Intention to treat, all included as randomized | Posted | Median | Inter-Quartile Range | days | Birth to one year |
|
|
|
|
| 2 |
| 175 |
| 16 |
| 175 |
| 0 |
| 175 |
| EG001 | Rotarix + No IPV | Rotarix vaccine at 10 and 17 weeks of age and routine oral polio vaccine series | 2 | 175 | 16 | 175 | 0 | 175 |
| EG002 | No Rotarix + IPV | No Rotarix vaccine and inactivated polio vaccine in place of the routine oral polio vaccine dose at 39 weeks | 1 | 175 | 20 | 175 | 0 | 175 |
| EG003 | No Rotarix + No IPV | No Rotarix vaccine and routine oral polio vaccine series | 0 | 175 | 21 | 175 | 0 | 175 |
| Respiratory illness | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Cyanosis | Cardiac disorders | Non-systematic Assessment |
|
| Sepsis | Infections and infestations | Non-systematic Assessment |
|
| Febrile Illness | General disorders | Non-systematic Assessment |
|
| Inguinal heria | Gastrointestinal disorders | Non-systematic Assessment |
|
| Convulsions | Nervous system disorders | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Non-systematic Assessment |
|
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| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D023321 |
| Poliovirus Vaccines |
| D014765 | Viral Vaccines |
| Sabin type 2 |
|
|
| Sabin type 3 |
|
|
| 0.2 |
| Mean Difference (Final Values) |
| 1.2 |
| 2-Sided |
| Superiority |
| Sabin type 3 shedding | t-test, 2 sided | 0.1 | Mean Difference (Final Values) | -1.3 | 2-Sided | Superiority |
| Sabin type 3 |
|
| Risk Difference (RD) |
| -3.1 |
| 2-Sided |
| 95 |
| -7.2 |
| 0.9 |
| Superiority |
| Risk Difference (RD) | 1.4 | 2-Sided | 95 | -3.2 | 6.1 | Superiority |
| Non-seroconversion Sabin type 2 |
|
|
| Non-seroconversion Sabin type 3 |
|
|
| Risk Difference (RD) |
| -24.3 |
| 2-Sided |
| 95 |
| -31.1 |
| -17.5 |
| Superiority |
| Risk Difference (RD) | -45.6 | 2-Sided | 95 | -52.6 | -38.0 | Superiority |