Vaccine Effectiveness of RV1 in a Naïve Population

• ClinicalTrials.gov Identifier: NCT01467037
• Recruitment Status: Completed
• First Posted: November 8, 2011
• Results First Posted: January 29, 2016
• Last Update Posted: April 19, 2016
• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Collaborators: Institut National en Santé Publique du Québec; Ministere de la Sante et des Services Sociaux; GlaxoSmithKline
• Information provided by (Responsible Party): Caroline Quach-Thanh, McGill University Health Centre/Research Institute of the McGill University Health Centre

Study Description

Brief Summary:

Rotavirus (RV) is the leading cause of severe gastroenteritis (GE) in young children. The cumulative risk of GE hospitalizations and hospital stays of < 24 hours is 1/25, which would amount to 13,600 Canadian children < 5 years. The incidence of nosocomial RV infections is an average of 8/10,000 patient-days in children < 5 years. An immunization program with a live-attenuated monovalent oral RV vaccine (RV1 - Rotarix® from GSK) will be implemented, free of charge, in the Province of Quebec in November 2011. To provide an accurate portrait of the disease and give critical information to the public health agencies as they struggle to control costs, we aim to evaluate the accuracy of surveillance for RV and other diseases with similar characteristics; estimate selection bias in passive laboratory-based surveillance; and estimate the agreement between surveillance time-series created from passive and active surveillance data sources.

Condition or disease	Intervention/treatment
Rotavirus Infections; Gastroenteritis; Diarrhea	Other: No intervention done

Detailed Description:

In November 2011, Quebec implemented a publicly-funded RV1 vaccination program with its routine administration at 2 and 4 months of age. From February 1, 2012 - May 31, 2014, we conducted prospective, active surveillance for acute rotavirus gastroenteritis at The Montreal Children's Hospital and Centre Hospitalier Universitaire Sainte-Justine, located in Montreal, and Centre Hospitalier Universitaire de Sherbrooke, located in Sherbrooke. Active surveillance was approved by Research Ethics Boards at each hospital.

Study Design

• Study Type: Observational
• Actual Enrollment: 374 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Vaccine Effectiveness of RV1 in a Naïve Population
• Study Start Date: February 2012
• Actual Primary Completion Date: December 2014
• Actual Study Completion Date: December 2014

Groups and Cohorts

Group/Cohort	Intervention/treatment
Rotavirus-negative; Patients with a negative result for rotavirus via enzyme immunoassay (EIA). No intervention done.	Other: No intervention done; Not applicable because no intervention was done.
Rotavirus-positive; Patients with a positive result for rotavirus via enzyme immunoassay (EIA). Rotavirus-positives were confirmed via real-time reverse-transcriptase polymerase chain reactions (RT-PCR). RT-PCR results were used in the event of discordant EIA results. Rotavirus genotyping was performed. No intervention done.	Other: No intervention done; Not applicable because no intervention was done.

Outcome Measures

Primary Outcome Measures :

1. Matched VE Participants [ Time Frame: From February 1, 2012 to May 31, 2014 ]

   RV1 vaccine effectiveness (VE) was investigated using a subset of active surveillance participants age-eligible to receive 2-doses of RV1 vaccine, defined as participants (i) <15 weeks of age as of program implementation (November 1, 2011), and (ii) ≥16 weeks of age at symptom onset. These ages corresponded to the maximum recommended age of administration for the first RV1 dose at program implementation, and the recommended age of second dose administration, respectively.

   We estimated RV1 VE of 2- versus 0-doses and ≥1- versus 0-doseto prevent rotavirus hospitalization or emergency visits. Only valid RV1 vaccinations administered ≥14 days prior to symptom onset were considered. Children vaccinated with RV5 (private market,minimal penetrance) were excluded.

Other Outcome Measures:

1. Vaccine Effectiveness of RV1 [ Time Frame: From February 1, 2012 to May 31, 2014 ]

   RV1 vaccine effectiveness (VE) was investigated using a subset of active surveillance participants age-eligible to receive 2-doses of RV1 vaccine, defined as participants (i) <15 weeks of age as of program implementation (November 1, 2011), and (ii) ≥16 weeks of age at symptom onset. These ages corresponded to the maximum recommended age of administration for the first RV1 dose at program implementation, and the recommended age of second dose administration, respectively.

   Only valid RV1 vaccinations administered ≥14 days prior to symptom onset were considered. RV1 VE was estimated as (1 - exposure odds ratio) × 100. Based upon our sampling scheme, the exposure odds ratio from our analyses approximates the rate ratio.

Biospecimen Retention:   Samples Without DNA

stool sample

Eligibility Criteria

• Ages Eligible for Study: 8 Weeks to 3 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

The Montreal Children's Hospital and the CHU Sainte-Justine are the 2 main pediatric hospitals in Montreal. With these 3 sites, 30% of the Quebec birth cohort will be captured and, given the concentration of children in the Montreal area, the participating hospitals will ensure that the study remains efficient in terms of resources. We elected Sherbrooke as an intermediate area; Montreal will represent an urban population.

Criteria

Inclusion Criteria:

• Child less than 3 years old

Cases:

• Acute gastroenteritis (within 7 days of hospital visit)
• able to provide a stool specimen for RV ELISA testing
• Rotavirus positive

Controls:

• Visited the ED or admitted for a non-rotavirus gastroenteritis
• Visited the ED or admitted for acute respiratory infections without gastroenteritis symptoms

Exclusion Criteria:

• Immunocompromised children
• Prior history of intussusception
• Admission to NICU between 6 to 15 weeks of life, for >6 weeks
• Child less than 56 days of life (8 weeks)
• Child vaccinated with Rotateq (Merck)

Contacts and Locations

Locations

Canada, Quebec

The Montreal Children's Hospital

Montreal, Quebec, Canada, H3H 1P3

Centre Hospitalier Universitaire Sainte-Justine

Montréal, Quebec, Canada, H3T 1C5

Centre Hospitalier Universitaire de Sherbrooke

Sherbrooke, Quebec, Canada, J1H 5N4

Sponsors and Collaborators

McGill University Health Centre/Research Institute of the McGill University Health Centre

Institut National en Santé Publique du Québec

Ministere de la Sante et des Services Sociaux

GlaxoSmithKline

Investigators

• Principal Investigator: Caroline Quach-Thanh, MD, MSc; McGill University Health Centre/Research Institute of the McGill University Health Centre
• Study Director: Caroline Quach-Thanh, MD, MSc; McGill University Health Centre/Research Institute of the McGill University Health Centre

More Information

Publications of Results:

Doll MK, Buckeridge DL, Morrison KT, Gagneur A, Tapiero B, Charest H, Quach C. Effectiveness of monovalent rotavirus vaccine in a high-income, predominant-use setting. Vaccine. 2015 Dec 16;33(51):7307-7314. doi: 10.1016/j.vaccine.2015.10.118. Epub 2015 Nov 3.

• Responsible Party: Caroline Quach-Thanh, MD, MSc, FRCPC, McGill University Health Centre/Research Institute of the McGill University Health Centre
• ClinicalTrials.gov Identifier: NCT01467037
• Other Study ID Numbers: MCH-ID-11-01
• First Posted: November 8, 2011
• Results First Posted: January 29, 2016
• Last Update Posted: April 19, 2016
• Last Verified: March 2016

Keywords provided by Caroline Quach-Thanh, McGill University Health Centre/Research Institute of the McGill University Health Centre:

Rotavirus; Gastroenteritis; Vaccination; Pediatrics

Additional relevant MeSH terms:

Rotavirus Infections; Gastroenteritis; Diarrhea; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Digestive System Diseases; Reoviridae Infections; RNA Virus Infections; Virus Diseases; Infections