Vaccine Effectiveness of RV1 in a Naïve Population

• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre (Other)
• Overall Status: Completed
• CT.gov ID: NCT01467037
• Collaborator: Institut National en Santé Publique du Québec (Other), Ministere de la Sante et des Services Sociaux (Other), GlaxoSmithKline (Industry)
• Enrollment: 374
• Locations: 3
• Duration (Months): 34
• Patients Per Site: 124.7
• Patients Per Site Per Month: 3.7

Study Details

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	Phase
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: Feb 1, 2012
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	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 [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 [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 8 Weeks to 3 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	The Montreal Children's Hospital	Montreal	Quebec	Canada	H3H 1P3
2	Centre Hospitalier Universitaire Sainte-Justine	Montréal	Quebec	Canada	H3T 1C5
3	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• 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: Nov 8, 2011
• Last Update Posted: Apr 19, 2016
• Last Verified: Mar 1, 2016

• Keywords provided by Caroline Quach-Thanh, MD, MSc, FRCPC, McGill University Health Centre/Research Institute of the McGill University Health Centre: Rotavirus; Gastroenteritis; Vaccination; Pediatrics
• Additional relevant MeSH terms: Rotavirus Infections; Gastroenteritis; Diarrhea

Study Results

Participant Flow

Recruitment Details	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.

Arm/Group Title	Vaccine Effectiveness Study Population
Arm/Group Description	Among patients eligible for active surveillance of acute gastroenteritis, patients aged <15 months at RV1 program implementation (November 1, 2011), AND aged ≥16 weeks at symptom onset
Period Title: Overall Study
STARTED	374
COMPLETED	374
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Rotavirus-negative	Rotavirus -Positive	Total
Arm/Group Description	All stool samples were initially tested for rotavirus via enzyme immunoassay. Patients with a negative result are included in this group.	All stool were initially tested for rotavirus via enzyme immunoassay. 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.	Total of all reporting groups
Overall Participants	342	32	374
Age (months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [months]	12.6 (6.3)	16.6 (6.5)	13 (6.4)
Sex: Female, Male (Count of Participants)
Female	154 45%	20 62.5%	174 46.5%
Male	188 55%	12 37.5%	200 53.5%
Region of Enrollment (participants) [Number]
Canada	342 100%	32 100%	374 100%
Rotavirus vaccination (participants) [Number]
RV-vaccination 0 dose	62 18.1%	24 75%	86 23%
RV-vaccination 1-dose	26 7.6%	1 3.1%	27 7.2%
RV-vaccination ≥2 doses	254 74.3%	7 21.9%	261 69.8%

Outcome Measures

1. Primary Outcome

Title	Matched VE Participants
Description	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.
Time Frame	From February 1, 2012 to May 31, 2014

Outcome Measure Data

Analysis Population Description

Rotavirus vaccination history by rotavirus disease status among matched VE participants

Arm/Group Title	Rotavirus-negative	Rotavirus-positive
Arm/Group Description	All stool samples were initially tested for rotavirus via enzyme immunoassay. Patients with a negative result are included in this group.	All stool were initially tested for rotavirus via enzyme immunoassay. Rotavirus positives were confirmed via realtime reversetranscriptase polymerase chain reactions (RTPCR). RTPCR results were used in the event of discordant EIA results. Rotavirus genotyping was performed.
Measure Participants	156	30
0-Doses	26 7.6%	22 68.8%
1 Dose	16 4.7%	1 3.1%
2 Doses	114 33.3%	7 21.9%

2. Other Pre-specified Outcome

Title	Vaccine Effectiveness of RV1
Description	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.
Time Frame	From February 1, 2012 to May 31, 2014

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	2 Versus 0 Doses	≥1 Versus 0 Dose
Arm/Group Description	We compared Rotavirus VE between patients that received 2 versus 0 doses of RV1.	We compared Rotavirus VE between patients that received 1 versus 0 dose of RV1.
Measure Participants	169	186
Number (95% Confidence Interval) [adjusted VE]	91.2	92.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rotavirus-negative
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted OR
	Estimated Value	0.088
	Confidence Interval	(2-Sided) 95%; 0.020 to 0.384
	Parameter Dispersion	Type: Value:
	Estimation Comments	Conditional logistic regression was used. Adjusted VE = (1 - adjusted OR) *100

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Rotavirus-positive
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted OR
	Estimated Value	0.075
	Confidence Interval	(2-Sided) 95%; 0.018 to 0.307
	Parameter Dispersion	Type: Value:
	Estimation Comments	Conditional logistic regression was used. Adjusted VE = (1 - adjusted OR) *100

Adverse Events

Adverse Event Reporting Description	Adverse events were not collected. We did not administer any medication nor vaccine.
Arm/Group Title	Vaccine Effectiveness Study Population
Arm/Group Description	Among patients eligible for active surveillance of acute gastroenteritis, patients aged <15 months at RV1 program implementation (November 1, 2011), AND aged ≥16 weeks at symptom onset
All Cause Mortality
	Vaccine Effectiveness Study Population
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Vaccine Effectiveness Study Population
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Vaccine Effectiveness Study Population
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.