Clinical trial NCT00595205: Intussusception Surveillance After Rotarix Introduction in Mexico
Official title: Post-Authorization Safety Study (PASS) of Post-Marketing Surveillance for Intussusception Following Rotarix™ Introduction Into the Instituto Mexicano Del Seguro Social (IMSS) in Mexico
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Intussusception (IS)
Rotavirus Vaccines
Keywords: vaccination
intussusception
Rotavirus
vaccine
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-01-16
Enrollment: 786
Sex: ALL
Maximum age (years): 364
Standard ages: CHILD
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All eligible children \< 1 year of age (children ineligible on day of first birthday) who are/have been treated at one of the study hospitals/medical facilities with definite intussusception.

Brief summary: GSK Biologicals' rotavirus vaccine, Rotarix™ has been recommended for universal use targeting infants through the Expanded Program on Immunization (EPI) in Mexico. This protocol describes a Phase IV safety study in Mexico designed to further evaluate the safety profile of Rotarix™ with regard to intussusception (IS). The data generated by this study will be useful for public health officers and policy makers in confirming the safety profile of Rotarix™.

Detailed description: Rationale for amendment 3:

The findings from the first year of the implementation of the active surveillance showed that most Lower Respiratory Tract-Related Post-Neonatal (LRTI) Mortality cases could not be included into the study, because most of the grieving parents refused to participate in the study. The European Medicines Agency Marketing Authorization Holders (EMEA MAH) also generated a substantial amount of additional clinical and post-marketing safety data throughout the world, which clearly indicated the absence of any safety signal when considering the LTRI-related fatalities. Therefore surveillance for LRTI mortality cases was removed from the study design. The number of sites was reduced from approximately 230 to about 60 to 90 in order to reflect the above mentioned change that reduced the need for so many sites. Additionally, passive surveillance for IS cases through the IMSS database was not feasible, due to restrictions of the IMSS internal policies and to the current limitations in the databases linkage and structure abilities.

Lastly, SAEs reporting procedures had to be adjusted according to the Council for International Organizations of Medical Sciences (CIOMS) Working Group V, 2001 publication such that there will be no expedited safety reporting for this study.

Design This is a post marketing ,Phase IV, observational, prospective, self-controlled case series, vaccine safety study including: a) hospital-based surveillance to monitor for the occurrence of IS through active surveillance; b) a self-controlled case series (SCCS) design/analysis to assess the temporal association with Rotarix™ of the IS ascertained through active surveillance.

The aim of the active hospital-based surveillance system is to identify all definite IS cases in children younger than one year of age (children ineligible on day of first birthday) among IMSS members. Surveillance will be conducted in approximately 60 to 90 IMSS health facilities with pediatric surgery service.

Study participation for children fitting the surveillance case definition of IS will include parental/guardian/legal representative interview, as well as a review of medical charts and vaccination records. Additional medical information will be collected through medical record review during hospitalization and after the child has been discharged.

Eligibility criteria: Inclusion Criteria:

A child's clinical episode will be defined as an IS case and deemed eligible for the study if he/she meets the following criteria:

* Subject is an IMSS affiliate
* Subject is being treated/has been treated/has been referred for treatment at one of the IMSS hospitals/medical facilities with IS during the study period.
* Male or female child is \<one year of age at the time of diagnosis of the IS (child becomes ineligible on the day of their first birthday)
* Subject is diagnosed with definite IS based on the Brighton criteria
* Written informed consent is obtained from the parent/guardian/legal representative of the subject Subjects meeting the above criteria will be eligible for inclusion in this study regardless of whether or not the subject has had a radiographically or surgically confirmed case of IS prior to the current episode.

Exclusion Criteria:

Not applicable

Primary outcomes:
measure: Occurrence of definite IS episodes within Day 0 to Day 30 following vaccination
timeFrame: 0- 30 days following Rotarix vaccination
Secondary outcomes:
measure: Occurrence of definite IS episodes within Day 0 to Day 15 following vaccination
timeFrame: Day 0 to Day 15 post Rotarix vaccination
measure: Yearly occurrence of definite IS episodes (regardless of vaccination status)
timeFrame: Assessed for the interim analysis and after study conclusion
Other outcomes:
Locations:
city: Mexico Df
country: Mexico
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Velázquez FR et al. Postmarketing surveillance to assess risk of intussusception following introduction of the G1P[8] human rotavirus vaccine in Mexico. Abstract presented at the Excellence in Paediatrics (EXPE). London, UK, 2-4 December 2010.