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Optimising Rotavirus Vaccine in Aboriginal Children (ORVAC)

Primary Purpose

Viral Gastroenteritis Due to Rotavirus

Status

Unknown status

Phase

Phase 4

Locations

Australia

Study Type

Interventional

Intervention

Rotarix (RV1)

Placebo

About this trial

This is an interventional prevention trial for Viral Gastroenteritis Due to Rotavirus focused on measuring Aboriginal, Rotavirus, Vaccine, Diarrhoea

Eligibility Criteria

6 Months - 12 Months (Child)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Aged ≥ 6 months and < 12 months
Identified as Aboriginal and/or Torres Strait Islander and/or South Sea Islander per attending legally responsible care-giver/parent.
Have received either one or two prior doses of RV1 vaccination as confirmed by checking the immunisation register.
Legally responsible care-giver/parent is willing for their infant to participate in the study and is aware of the requirements of the protocol.
Legally responsible care-giver/parent is willing to allow other parties involved in the treatment of their child (including general practitioner, medical centre staff and any other medical professionals the child may be a patient of for the duration of the trial) to be notified of their participation in the trial and for participation in the trial to be recorded within the Northern Territory Immunisation Register.
The legally responsible care-giver/parent is willing to allow the study team to obtain a vaccination history from Northern Territory Immunisation Register and/or the Australian Childhood Immunisation Register (ACIR) and/or local provider.
The legally responsible care-giver/parent is willing to allow the study team to obtain a medical history from hospitalisation and laboratory databases, the disease notification register, the participant's electronic medical records and/or from the participant's primary care provider for the period from enrolment to age 36 months
Informed consent for the infant's/child's participation in the study has been given by the legally responsible care-giver/parent

Exclusion Criteria:

Has any contraindication for RV1 vaccination including:

Severe combined immunodeficiency, any history of intussusception, any history of hypersensitivity to any vaccine component, or an uncorrected gastrointestinal tract malformation, receipt of more than two weeks of immunosuppressant or immune modifying drugs, (e.g. prednisolone > 0.5mg/kg/day) within 28 days of enrolment, confirmed or suspected severe immunosuppressive or immunodeficient conditions, including human immunodeficiency virus (HIV) infection
Receipt of any rotavirus vaccination other than RV1
Receipt in the previous 3 months of any blood products including immunoglobulin
Has received no prior doses or > two prior doses of RV1 vaccination
Medical condition or treatment with medication which in the opinion of the clinic staff would make the child unsuitable for the trial
Previously enrolled in the trial

Sites / Locations

Menzies School of Health ResearchRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Rotarix

Placebo

Arm Description

Rotarix (RV1) vaccine, 1mL liquid suspension administered orally.

Placebo liquid suspension manufactured to mimic Rotarix (RV1) vaccine, 1ml administered orally

Outcomes

Primary Outcome Measures

Time from randomisation to medical attendance for acute gastroenteritis or acute diarrhoea illness

Time from randomisation to medical attendance (hospitalisation, emergency department presentation, medical clinic presentation) for which the primary reason for presentation is presumed or confirmed acute gastroenteritis or acute diarrhoea illness between randomisation and age 36 months.

Occurrence of anti-rotavirus IgA seroconversion

Anti-rotavirus IgA seroconversion, defined as serum anti-rotavirus IgA > 20U/ ml 28 to 55 days post RV1/placebo among infants with anti-rotavirus serum IgA < 20U/ ml before RV1/placebo, to be summarised as the proportion of all children per group.

Secondary Outcome Measures

Time from randomisation to hospitalisation for acute gastroenteritis or acute diarrhoea illness

Time from randomisation to hospitalisation for which the primary coded reason for admission is presumed or confirmed acute gastroenteritis or acute diarrhoea illness between randomisation and age 36 months.

Time from randomisation to hospitalisation for rotavirus confirmed diarrhoea illness

Time from randomisation to hospitalisation for which rotavirus confirmed diarrhoea illness occurs between randomisation and age 36 months.

Time from randomisation to Rotavirus infection

Time from randomisation to rotavirus infection meeting the jurisdictional case definition between randomisation and age 36 months.

Change in anti-rotavirus IgA log titre between administration of intervention (RV1/placebo) and 28 to 55 days post dose

Change in anti-rotavirus IgA log titre between administration of intervention (RV1/placebo) and 28 to 55 days post dose, to be summarised as the proportion of all children per group.

Occurrence of intussusception fulfilling Brighton criteria (see Appendix A)

The occurrence of intussusception fulfilling Brighton criteria (see Appendix A) within the first 28 days after RV1/placebo administration, to be summarised as the proportion of all children per group.

Occurrence of a serious adverse event

Serious adverse events between randomisation and age 36 months, to be summarised as the proportion of all children per group.

Medical attendance for confirmed acute gastroenteritis or acute diarrhoea illness between randomisation and 36 months gastroenteritis or acute diarrhoea illness.

Medical attendance (hospitalisation, emergency department presentations, medical clinic presentations) from the time of randomisation to age 36 months, for which the primary reason for presentation is presumed or confirmed acute gastroenteritis or acute diarrhoea illness, to be summarised as the proportion of all children per group.

Full Information

NCT ID

NCT02941107

First Posted

October 19, 2016

Last Updated

November 5, 2020

Sponsor

Telethon Kids Institute

Collaborators

Menzies School of Health Research

1. Study Identification

Unique Protocol Identification Number

NCT02941107

Brief Title

Optimising Rotavirus Vaccine in Aboriginal Children

Acronym

ORVAC

Official Title

The ORVAC Trial: A Phase IV, Double-blind, Randomised, Placebo-controlled Clinical Trial of a Third Scheduled Dose of RV1 Rotavirus Vaccine in Australian Indigenous Infants to Improve Protection Against Gastroenteritis

Study Type

Interventional

2. Study Status

Record Verification Date

October 2020

Overall Recruitment Status

Unknown status

Study Start Date

March 27, 2018 (Actual)

Primary Completion Date

December 2020 (Anticipated)

Study Completion Date

December 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Telethon Kids Institute

Collaborators

Menzies School of Health Research

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Detailed Description

Australian Indigenous children, particularly those living in remote communities, suffer a disproportionately high burden of rotavirus gastroenteritis disease. Despite the introduction of rotavirus vaccine into the Northern Territory (NT) Immunisation Schedule in 2006, the rate of hospitalization for rotavirus in NT Aboriginal children < 5 years continues to be high, and the rate ratio of rotavirus hospitalisations for Indigenous versus non-Indigenous children has actually increased. The reasons for sub-optimal vaccine response are not completely understood, but both reduced vaccine immune responses and low vaccine coverage are likely to be important factors. This study will enrol Aboriginal infants aged 6 months to < 12 months old who have received one or two prior doses of RV1. The coprimary aim is to determine whether an oral dose of RV1 vaccine at age 6 months to less than 12 months, compared to placebo, results in an increase in the average time to medical attendance for gastroenteritis before age 36 months (co-primary endpoint 1), and/ or superior immune protection against rotavirus gastroenteritis assessed approximately 1 to 2 months after vaccination (co-primary endpoint 2), in Australian Indigenous children. This is a phase IV, randomised, placebo-controlled Bayesian trial with two strata representing residency based on a standard geographical classification of remoteness. It has the following key features: Double-blind, randomised, placebo-controlled trial; The procedures for enrolment, intervention, end-point and analysis are based on the principles of pragmatic trial design; Non-fixed sample size up to 1,000 participants based on Bayesian stopping rules; Fixed 1:1 enrolment into the active and control arm throughout the trial; Frequent interim analyses can result in the trial stopping early for futility or expected success.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Viral Gastroenteritis Due to Rotavirus

Keywords

Aboriginal, Rotavirus, Vaccine, Diarrhoea

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

1000 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Rotarix

Arm Type

Experimental

Arm Description

Rotarix (RV1) vaccine, 1mL liquid suspension administered orally.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo liquid suspension manufactured to mimic Rotarix (RV1) vaccine, 1ml administered orally

Intervention Type

Drug

Intervention Name(s)

Rotarix (RV1)

Other Intervention Name(s)

ROTARIX™

Intervention Description

ROTARIX™ (RV1) is a live-attenuated human monovalent oral vaccine containing attenuated G1P[8] human rotavirus strain sponsored and distributed in Australia by GlaxoSmithKline Biologicals where it is licensed for the prevention of rotavirus gastroenteritis.

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

Viscosweet

Intervention Description

The placebo for this trial will be Viscosweet, a clear and flavoured solution used as a pharmaceutical excipient repackaged into a labelled syringe identical to the active and firmly sealed with an end cap.

Primary Outcome Measure Information:

Title

Time from randomisation to medical attendance for acute gastroenteritis or acute diarrhoea illness

Description

Time Frame

Randomisation to 36 months

Title

Occurrence of anti-rotavirus IgA seroconversion

Description

Time Frame

28-55 Days post RV1/placebo administration

Secondary Outcome Measure Information:

Title

Time from randomisation to hospitalisation for acute gastroenteritis or acute diarrhoea illness

Description

Time Frame

Randomisation to 36 months

Title

Time from randomisation to hospitalisation for rotavirus confirmed diarrhoea illness

Description

Time from randomisation to hospitalisation for which rotavirus confirmed diarrhoea illness occurs between randomisation and age 36 months.

Time Frame

Randomisation to 36 months

Title

Time from randomisation to Rotavirus infection

Description

Time from randomisation to rotavirus infection meeting the jurisdictional case definition between randomisation and age 36 months.

Time Frame

Randomisation to 36 months

Title

Change in anti-rotavirus IgA log titre between administration of intervention (RV1/placebo) and 28 to 55 days post dose

Description

Change in anti-rotavirus IgA log titre between administration of intervention (RV1/placebo) and 28 to 55 days post dose, to be summarised as the proportion of all children per group.

Time Frame

Randomisation and 28-55 days post RV1/placebo administration

Title

Occurrence of intussusception fulfilling Brighton criteria (see Appendix A)

Description

Time Frame

Within the first 28 days of RV1/placebo administration

Title

Occurrence of a serious adverse event

Description

Serious adverse events between randomisation and age 36 months, to be summarised as the proportion of all children per group.

Time Frame

Randomisation to 36 months

Title

Medical attendance for confirmed acute gastroenteritis or acute diarrhoea illness between randomisation and 36 months gastroenteritis or acute diarrhoea illness.

Description

Time Frame

Randomisation to 36 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Months

Maximum Age & Unit of Time

12 Months

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Aged ≥ 6 months and < 12 months Identified as Aboriginal and/or Torres Strait Islander and/or South Sea Islander per attending legally responsible care-giver/parent. Have received either one or two prior doses of RV1 vaccination as confirmed by checking the immunisation register. Legally responsible care-giver/parent is willing for their infant to participate in the study and is aware of the requirements of the protocol. Legally responsible care-giver/parent is willing to allow other parties involved in the treatment of their child (including general practitioner, medical centre staff and any other medical professionals the child may be a patient of for the duration of the trial) to be notified of their participation in the trial and for participation in the trial to be recorded within the Northern Territory Immunisation Register. The legally responsible care-giver/parent is willing to allow the study team to obtain a vaccination history from Northern Territory Immunisation Register and/or the Australian Childhood Immunisation Register (ACIR) and/or local provider. The legally responsible care-giver/parent is willing to allow the study team to obtain a medical history from hospitalisation and laboratory databases, the disease notification register, the participant's electronic medical records and/or from the participant's primary care provider for the period from enrolment to age 36 months Informed consent for the infant's/child's participation in the study has been given by the legally responsible care-giver/parent Exclusion Criteria: Has any contraindication for RV1 vaccination including: Severe combined immunodeficiency, any history of intussusception, any history of hypersensitivity to any vaccine component, or an uncorrected gastrointestinal tract malformation, receipt of more than two weeks of immunosuppressant or immune modifying drugs, (e.g. prednisolone > 0.5mg/kg/day) within 28 days of enrolment, confirmed or suspected severe immunosuppressive or immunodeficient conditions, including human immunodeficiency virus (HIV) infection Receipt of any rotavirus vaccination other than RV1 Receipt in the previous 3 months of any blood products including immunoglobulin Has received no prior doses or > two prior doses of RV1 vaccination Medical condition or treatment with medication which in the opinion of the clinic staff would make the child unsuitable for the trial Previously enrolled in the trial

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Tom Snelling

Phone

0401355389

tom.snelling@telethonkids.org.au

First Name & Middle Initial & Last Name or Official Title & Degree

Nelly Newall

nelly.newall@telethonkids.org.au

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Tom Snelling

Organizational Affiliation

Telethon Kids Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Menzies School of Health Research

City

Darwin

State/Province

Northern Territory

ZIP/Postal Code

0810

Country

Australia

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Tom Snelling, Dr

tom.snelling@telethonkids.org.au

First Name & Middle Initial & Last Name & Degree

Dennis Bonney, Dr

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

IPD (de-identified) may be shared with other research teams subject to approval of the statistical analysis plan, data transfer agreement and appropriate ethics. However, prior approvals may be required from lead ethics

IPD Sharing Time Frame

post publication of study results

IPD Sharing Access Criteria

Researchers need to supply a statistical analysis plan and appropriate Ethics approvals

Citations:

PubMed Identifier

35134951

Citation

Middleton BF, Danchin M, Jones MA, Leach AJ, Cunliffe N, Kirkwood CD, Carapetis J, Gallagher S, Kirkham LA, Granland C, McNeal M, Marsh JA, Waddington CS, Snelling TL. Immunogenicity of a Third Scheduled Dose of Rotarix in Australian Indigenous Infants: A Phase IV, Double-blind, Randomized, Placebo-Controlled Clinical Trial. J Infect Dis. 2022 Nov 1;226(9):1537-1544. doi: 10.1093/infdis/jiac038.

Results Reference

derived

PubMed Identifier

32843086

Citation

Jones MA, Graves T, Middleton B, Totterdell J, Snelling TL, Marsh JA. The ORVAC trial: a phase IV, double-blind, randomised, placebo-controlled clinical trial of a third scheduled dose of Rotarix rotavirus vaccine in Australian Indigenous infants to improve protection against gastroenteritis: a statistical analysis plan. Trials. 2020 Aug 26;21(1):741. doi: 10.1186/s13063-020-04602-w.

Results Reference

derived

PubMed Identifier

31727664

Citation

Middleton BF, Jones MA, Waddington CS, Danchin M, McCallum C, Gallagher S, Leach AJ, Andrews R, Kirkwood C, Cunliffe N, Carapetis J, Marsh JA, Snelling T. The ORVAC trial protocol: a phase IV, double-blind, randomised, placebo-controlled clinical trial of a third scheduled dose of Rotarix rotavirus vaccine in Australian Indigenous infants to improve protection against gastroenteritis. BMJ Open. 2019 Nov 14;9(11):e032549. doi: 10.1136/bmjopen-2019-032549.

Results Reference

derived

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Optimising Rotavirus Vaccine in Aboriginal Children

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