The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product. Before prescribing any product mentioned in this Register, healthcare professionals should consult prescribing information for the product approved in their country. GSK Medicine: Rotarix TM (HRV): GlaxoSmithKline (GSK) Biologicals oral live attenuated human rotavirus (HRV) vaccine. Study No.: 111562 (EPI-ROTA-111562) Title: Case-control study to evaluate the vaccine effectiveness of Rotarix TM against rotavirus severe gastroenteritis (RV SGE) among hospitalized children born after 6 March 2006 and at least 12 weeks of age, in Belem, Brazil. Rationale: To evaluate the vaccine effectiveness (VE) of HRV full series (2 doses) vaccination in preventing rotavirus (RV) severe gastroenteritis (SGE) hospitalizations among infants in Brazil. The study was conducted in 2 parts: a Case-Control Part (for a period of 12 months from the date of study initiation) and a RV Strain Surveillance Part (for a period of 36 months from the date of study initiation), which was conducted for the hospitalized subjects enrolled and for whom stool samples were tested positive for RV. Study Period: 14-May-2008 to 11-May-2011 Objectives: Primary objective To estimate the effectiveness of HRV full series (2 doses) vaccination in preventing RV SGE among children hospitalized at four clinics/hospitals in Belem area, who were born after 6 March 2006 and were at least 12 weeks of age. Secondary objectives To estimate the proportion of SGE among all clinic/hospital admissions in children born after 6 March 2006 and at least 12 weeks of age. To estimate the proportion of all RV SGE admissions in children born after 6 March 2006 and at least 12 weeks of age. To determine the distribution of RV SGE clinics/hospitals admissions by the age of the child and month of year. To determine the RV serotypes causing RV SGE among hospitalized children born after 6 March 2006 and at least 12 weeks of age. To estimate the effectiveness of HRV vaccine in preventing RV SGE hospitalization in children born after 6 March 2006 and at least 12 weeks of age, when used in typical real life situations (i.e. 1 or 2 doses). Indication: Prevention of RV SGE in infants aged at least 12 weeks. Study Investigators/Centers: GSK conducted study, 4 centers in Brazil. Research Methods: Data Source: Parents/guardians interview, review of medical records and vaccination cards, stool sampling Study Design: A hospital-based, multi-centered, matched case-control study. Study Population: Cases: Male or female children born after 6 March 2006 and at least 12 weeks of age, admitted to the study clinics/hospitals for SGE during the study period with onset of SGE 14 days prior to admission, whose stool samples tested positive (by Enzyme-Linked Immunosorbent Assay [ELISA]) for RV at hospital admission or during the first 48 hours of hospitalization. Controls: Children born within 6 weeks (maximum) from the date of birth of the case, admitted for non-gastroenteritis (GE) causes at the same clinic/hospital as the case were included in the study as hospital controls. Children born within 8 weeks from the date of birth of the case, living in the same neighborhood as the case for at least 3 consecutive months without any GE or SGE symptoms were included in the study as neighborhood controls. For all the subjects, written informed consent was obtained from the subjects parents or guardians. Study Exposures, Outcomes: The study groups were as follows: : included subjects hospitalized for SGE and tested positive for RV. Hos-con (Hospitalized controls) Group: included subjects hospitalized for non-ge causes in the same hospital as the case Nei-con (Neighborhood controls) Group: included subjects residing in the same area as the case at least for 3 consecutive months, without any symptoms of GE or SGE Primary outcome:
Risk of ELISA-confirmed RV SGE in children fully vaccinated with HRV vaccine (born after 6 March 2006 and at least 12 weeks of age), compared to risk of ELISA-confirmed RV SGE in children (born after 6 March 2006 and at least 12 weeks of age). Secondary outcome(s): Risk of ELISA-confirmed RV SGE in children vaccinated with at least one dose of HRV vaccine (born after 6 March 2006 and at least 12 weeks of age), compared to risk of ELISA-confirmed RV SGE in children (born after 6 March 2006 and at least 12 weeks of age). Occurrence of SGE among children born after 6 March 2006 and at least 12 weeks of age and admitted to study clinics/hospitals for SGE. Occurrence of RV genotypes among children born after 6 March 2006 and at least 12 weeks of age. Data Analysis Methods: The analyses were performed on the Screened cohort, the Total enrolled cohort, the According To Protocol (ATP) cohort, the ATP cohort for and matched neighborhood controls and the ATP cohort for and matched hospital controls: - The Screened cohort included all children born after 6 March 2006 and at least 12 weeks of age who were admitted to the hospital for symptoms of SGE. - The Total enrolled cohort included all children ( and controls) enrolled into the study. - The ATP cohort included all children ( and controls) who were enrolled into the surveillance until the study end, meeting all inclusion/exclusion criteria and complying with the study procedures. - The ATP cohort for and matched neighborhood controls included all valid and their matched neighborhood controls (i.e. those meeting all eligibility criteria, complying with the procedures defined in the protocol). - The ATP cohort for and matched hospital controls included all valid and their matched hospital controls (i.e. those meeting all eligibility criteria, complying with the procedures defined in the protocol). Primary objective: The VE (estimated as 1 minus the matched odds ratio multiplied by 100%) of full vaccination series of HRV vaccine in preventing RV SGE associated hospital admissions for against matched neighborhood controls and matched hospital controls was calculated using 95% Confidence Interval (CI) for the Case Control Part. Only who received HRV vaccine at least 14 days before the onset of SGE were considered as vaccinated for analysis purposes. Secondary objectives: The following analyses were performed for the Case-Control Part and/ or the RV Strain surveillance Part : - The proportion of all hospital admissions caused by SGE was calculated, with its 95% confidence interval (CI), as the total number of SGE hospitalizations out of total number of hospitalizations. - The proportion of SGE hospitalizations among children attributable to RV was calculated, with its, as the total number of confirmed RV SGE hospitalizations out of total number of SGE hospitalizations. - The percentage of RVSGE hospitalizations by age groups and RVSGE seasonal distribution by month of a year and by month and age group were tabulated.by - The VE of partial vaccination series was calculated as the VE for the full vaccination series. - The distribution of RV genotypes was also tabulated. Limitations: Not applicable. Study Results: Demographics/Baseline Characteristics Case-Control Part Hos-con Group Nei-con Group Planned, N 230 230 230 N (Total enrolled cohort) 538 516 348 Females: Males 265:273 241:275 158:190 Mean Age, months (SD) 16.9 (6.98) 18.3 (7.35) 17.5 (7.04) Demographics/Baseline Characteristics Strain Surveillance Part Planned, N* 230 N (Total enrolled cohort) 1078 Females: Males 509:569 Mean Age, months (SD) 18.5 (9.38) *Planned number of for the Case Control part of the study Primary Outcome Measure: Effectiveness of HRV vaccine full series vaccination ( against neighborhood control) (ATP cohort for and matched neighborhood controls) Case-Control Part VE (in %) LL UL Sens. + Sens. -
fully HRV vaccine fully HRV vaccine Neicon Group Nei-con Group 168 81 218 31 75.76 58.14 85.96 77.78 71.21 = 95% confidence interval; LL= lower limit, UL= upper limit Sens. + = and controls with other or unknown Rotavirus vaccination status are assumed respectively and vaccinated Sens. - = and controls with other or unknown Rotavirus vaccination status are assumed respectively vaccinated and Primary Outcome Measure: Effectiveness of HRV vaccine full series vaccination ( against hospital controls) (ATP cohort for and matched hospital controls) Case-Control Part fully HRV vaccine fully HRV vaccine Hoscon Group Hos-con Group VE (in %) LL UL Sens. + Sens. - 211 101 243 69 40.00 14.18 58.05 51.99 21.25 = 95% confidence interval; LL= lower limit, UL= upper limit Sens. + = and controls with other or unknown Rotavirus vaccination status are assumed respectively and vaccinated Sens. - = and controls with other or unknown Rotavirus vaccination status are assumed respectively vaccinated and Secondary Outcome Measure: Effectiveness of HRV vaccine partial or full series vaccination ( against neighborhood controls) (ATP cohort for and matched neighborhood controls) Case-Control Part partial or full HRV vaccine partial or full HRV vaccine Nei-con Group Nei-con Group VE (in %) LL UL Sens. + Sens. - 239 92 287 44 62.34 42.28 75.43 65.48 58.44 = 95% confidence interval; LL= lower limit, UL= upper limit Sens. + = and controls with other or unknown Rotavirus vaccination status were assumed respectively and vaccinated Sens. - = and controls with other or unknown Rotavirus vaccination status were assumed respectively vaccinated and Secondary Outcome Measure: Effectiveness of HRV vaccine partial or full series vaccination ( against hospital controls) (ATP cohort for and matched hospital controls) Case-Control Part partial or full HRV vaccine partial or full HRV Hos-con Group Hos-con Group VE (in %) LL UL Sens. + Sens. - 319 125 365 79 44.23 23.10 59.55 54.32 25.96 = 95% confidence interval; LL= lower limit, UL= upper limit Sens. + = and controls with other or unknown Rotavirus vaccination status were assumed respectively and vaccinated Sens. - = and controls with other or unknown Rotavirus vaccination status were assumed respectively vaccinated and Secondary Outcome Measure: Proportion of hospitalizations attributable to SGE (Screened cohort) Case-Control Part SGE hospitalizations hospitalizations Proportion (in %) LL UL 4692 10828 43.33 42.40 44.27 = 95% confidence interval; LL= lower limit, UL= upper limit Secondary Outcome Measure: Proportion of SGE hospitalizations attributable to RV (Screened cohort) Case-Control Part RV SGE hospitalizations SGE hospitalizations Proportion (in %) LL UL
906 4692 19.31 18.19 20.47 = 95% confidence interval; LL= lower limit, UL= upper limit Secondary Outcome Measure: Distribution of RV serotypes (G-type) (ATP Cohort) Case-Control Part N = 538 Characteristics Categories n % LL UL Serotype G1 15 2.8 1.6 4.6 G2 492 91.4 88.8 93.7 G4 1 0.2 0.0 1.0 G9 5 0.9 0.3 2.2 G12 13 2.4 1.3 4.1 G1 G2 8 1.5 0.6 2.9 Untypeable 4 0.7 0.2 1.9 N = number of RV SGE subjects % = n/n x 100 = 95% confidence interval; LL= lower limit, UL= upper limit Secondary Outcome Measure: Distribution of RV genotypes (P-type) (ATP Cohort) Case-Control Part N = 538 Characteristics Categories n % LL UL Genotype P[4] 445 82.7 79.2 85.8 P[6] 31 5.8 3.9 8.1 P[8] 14 2.6 1.4 4.3 P[4] P[6] 32 5.9 4.1 8.3 P[4] P[8] 4 0.7 0.2 1.9 P[6] P[8] 2 0.4 0.0 1.3 P[4] P[6] P[8] 8 1.5 0.6 2.9 Untypeable 2 0.4 0.0 1.3 N = number of RV SGE subjects % = n/n x 100 = 95% confidence interval; LL= lower limit, UL= upper limit Secondary Outcome Measure: Distribution of RV genotypes (G&P-type) (ATP cohort) Case-Control Part N = 538 Characteristics Categories n % LL UL Genotype G1 P[6] 1 0.2 0.0 1.0 G1 P[8] 11 2.0 1.0 3.6 G2 P[4] 441 82.0 78.5 85.1 G2 P[6] 16 3.0 1.7 4.8 G9 P[4] 2 0.4 0.0 1.3 G9 P[6] 1 0.2 0.0 1.0 G9 P[8] 2 0.4 0.0 1.3 G12 P[6] 11 2.0 1.0 3.6 G1-Mixed 3 0.6 0.1 1.6 G2-Mixed 34 6.3 4.4 8.7 G4-Mixed 1 0.2 0.0 1.0 G12-Mixed 2 0.4 0.0 1.3 G2-UNTYP 1 0.2 0.0 1.0 Mixed-P[4] 2 0.4 0.0 1.3 Mixed-P[8] 1 0.2 0.0 1.0 Mixed-Mixed 5 0.9 0.3 2.2
UNTYP-P[6] 2 0.4 0.0 1.3 UNTYP-Mixed 1 0.2 0.0 1.0 UNTYP-UNTYP 1 0.2 0.0 1.0 N = number of RV SGE subjects % = n/n x 100 = 95% confidence interval; LL= lower limit, UL= upper limit Mixed = Mixed sero or geno types Mixed-Mixed = both mixed sero and geno types UNTYP = Untypeable UNTYP-UNTYP = Untypeable of both sero and geno type Secondary Outcome Measure: Seasonal distribution of RV SGE by month and age group (ATP Cohort) Case- Control Part Month and Year Age group (months) SGE tested for RV* MAY2008 3-5 11 6-11 48 12-23 88 24 12 Others 1 JUN2008 3-5 16 6-11 100 12-23 141 24 21 Others 1 JUL2008 3-5 14 6-11 113 12-23 213 24 44 Others 1 AUG2008 3-5 20 6-11 131 12-23 236 24 65 Others 4 SEP2008 3-5 14 6-11 82 12-23 124 24 36 Others 2 OCT2008 3-5 17 6-11 66 12-23 113 24 24 Others 2 NOV2008 3-5 23 6-11 100 12-23 98 24 30 DEC2008 3-5 27 6-11 98 12-23 104 24 24 Others 3 JAN2009 3-5 38 6-11 108
12-23 162 24 49 Others 4 FEB2009 3-5 26 6-11 97 12-23 163 24 45 Others 5 MAR2009 3-5 26 6-11 93 12-23 148 24 58 Others 2 APR2009 3-5 25 6-11 77 12-23 164 24 103 MAY2009 3-5 7 6-11 26 12-23 49 24 20 Others 1 *From the SGE logbook Secondary Outcome Measure: Proportion of hospitalizations attributable to SGE (Screened cohort) Strain Surveillance Part SGE hospitalizations (n) hospitalizations (N) Proportion (in %) LL UL 10031 17542 57.18 56.45 57.92 % = n/ subjects with available results x 100 LL, UL = 95% Lower and Upper exact confidence limits Secondary Outcome Measure: Proportion of SGE hospitalizations attributable to RV (Screened cohort) Strain Surveillance Part RV SGE hospitalizations (n) SGE hospitalizations (N) Proportion (in %) LL UL 1726 10031 17.21 16.47 17.96 % = n/ subjects with available results x 100 = 95% confidence interval; LL= lower limit, UL= upper limit Secondary Outcome Measure: hospitalizations of RV SGE by age groups (ATP cohort) Strain Surveillance Part N = 1078 Age (months) n % 3-5 27 2.50 6-11 217 20.13 12-23 547 50.74 24 287 26.62 N = RV SGE hospitalizations n = subjects in a given category % = n/n*100 Secondary Outcome Measure: Distribution of RV serotypes (G-type) (ATP cohort) Strain Surveillance Part N = 1076 Characteristics Categories n % Serotype G1 264 24.54 G2 736 68.40 G3 1 0.09
G4 1 0.09 G9 42 3.90 G12 13 1.21 UNTYP 81 7.53 Others 0 0.00 N = number of RV SGE hospitalizations that were serotyped % = n / N x 100 UNTYP = Untypeable Secondary Outcome Measure: Distribution of RV genotypes (P-type) (ATP cohort) Strain Surveillance Part N = 1076 Characteristics Categories n % Genotype P4 718 66.73 P6 147 13.66 P8 224 20.82 P9 0 0.00 UNTYP 70 6.51 Others 0 0.00 N = number of RV SGE hospitalizations that were serotyped % = n / N x 100 UNTYP = Untypeable Secondary Outcome Measure: Distribution of RV genotypes (G&P-type) (ATP cohort) Strain Surveillance Part N = 1076 Characteristics Categories n % Genotype G-Mixed P-Mixed 17 1.58 G-Mixed P[4] 27 2.51 G-Mixed P[6] 2 0.19 G-Mixed P[8] 7 0.65 G-Mixed UNTYP 7 0.65 G12 P-Mixed 2 0.19 G12 P[6] 11 1.02 G1 P-Mixed 10 0.93 G1 P[4] 3 0.28 G1 P[6] 10 0.93 G1 P[8] 160 14.87 G1 UNTYP 23 2.14 G2 P-Mixed 43 4.00 G2 P[4] 615 57.16 G2 P[6] 19 1.77 G2 UNTYP 10 0.93 G3 P[8] 1 0.09 G4 P-Mixed 1 0.09 G9 P[4] 3 0.28 G9 P[6] 2 0.19 G9 P[8] 21 1.95 G9 UNTYP 1 0.09 UNTYP P-Mixed 1 0.09 UNTYP P[6] 51 4.74 UNTYP UNTYP 29 2.70 N = number of RV SGE hospitalizations that were serotyped % = n / N x 100 UNTYP = Untypeable
Note: G-Mixed includes more than one G types and P-Mixed includes more than one P types Secondary Outcome Measure: Seasonal distribution of RV SGE by month of a year (ATP cohort*) Strain Surveillance Part Month & Year of RV+ (n) SGE hospitalizations % of RV+ hospitalization tested for RV (N) MAY2008 18 160 11.25 JUN2008 48 279 17.20 JUL2008 96 385 24.94 AUG2008 126 456 27.63 SEP2008 33 258 12.79 OCT2008 31 222 13.96 NOV2008 8 251 3.19 DEC2008 12 256 4.69 JAN2009 24 361 6.65 FEB2009 24 336 7.14 MAR2009 41 327 12.54 APR2009 64 369 17.34 MAY2009 31 194 15.98 JUN2009 17 160 10.63 JUL2009 53 238 22.27 AUG2009 54 213 25.35 SEP2009 37 168 22.02 OCT2009 14 103 13.59 NOV2009 6 112 5.36 DEC2009 6 100 6.00 JAN2010 9 188 4.79 FEB1200 9 249 3.61 MAR2010 8 251 3.19 APR2010 16 195 8.21 MAY2010 18 74 24.32 JUN2010 25 149 16.78 JUL2010 49 218 22.48 AUG2010 74 262 28.24 SEP2010 26 149 17.45 OCT2010 21 146 14.38 NOV2010 15 122 12.30 DEC2010 12 118 10.17 JAN2011 17 134 12.69 FEB2011 8 154 5.19 MAR2011 7 124 5.65 APR2011 17 123 13.82 MAY2011 4 39 10.26 *From the SGE logbook % = n/n x 100 Conclusion: The VE of HRV vaccine in preventing RV SGE associated hospital admissions was 75.76% for against matched neighborhood controls and 40.00% for against matched hospital controls. Date Updated: 06-September-2013