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Trial registered on ANZCTR


Registration number
ACTRN12616001230448
Ethics application status
Approved
Date submitted
30/08/2016
Date registered
5/09/2016
Date last updated
19/11/2019
Date data sharing statement initially provided
19/11/2019
Date results information initially provided
19/11/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Impact of conjugate versus polysaccharide quadrivalent ACWY vaccine on meningococcal carriage among Hajj pilgrims
Scientific title
Meningococcal disease at Hajj: Vaccine effects on short to medium-term meningococcal nasopharyngeal carriage: comparison of conjugate and polysaccharide quadrivalent ACWY vaccine
Secondary ID [1] 290054 0
Unknown
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
meningococcal carriage 300108 0
Condition category
Condition code
Infection 299990 299990 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Meningococcal group A, C, W135 and Y conjugate vaccine.

A single 0.5 ml dose of the reconstituted vaccine (meningococcal A,C,W&Y conjugate vaccine) will be given intramuscularly and must be administered 1-2 months prior to departing for Hajj.
Intervention code [1] 295777 0
Prevention
Comparator / control treatment
Meningococcal group A, C, W135 and Y polysaccharide vaccine.

A single 0.5 ml dose of the reconstituted vaccine (meningococcal A,C,W&Y polysaccharide vaccine) will be given subcutaneously and must be administered 1-2 months prior to departing for Hajj.
Control group
Active

Outcomes
Primary outcome [1] 299477 0
To compare the prevalence of serogroup-specific meningococcal carriage among Hajj pilgrims receiving quadrivalent meningococcal conjugate vaccine to that in those receiving quadrivalent meningococcal polysaccharide vaccine within sixty days after completion of Hajj .

Pharyngeal swabs will be obtained from the participants for microbiological testing. The rates of pharyngeal carriage of meningococcci in both vaccine arms will be compared by Pearson's chi-squared test in order to determine if the prevalence of serogroup-specific meningococcal carriage in Hajj pilgrims receiving quadrivalent meningococcal conjugate vaccine is different from that in pilgrims receiving quadrivalent meningococcal polysaccharide vaccine within 60 days (or 2 months) after completion of Hajj journey.
Timepoint [1] 299477 0
Within sixty days after completion of Hajj journey.
Secondary outcome [1] 327292 0
Study the changes in pharyngeal carriage rates of meningococci from prior to, until 2 months after vaccination,

Pharyngeal swabs will be obtained from the participants for microbiological testing. The rates of pharyngeal carriage of meningococcci before and after vaccination in each study arm will be compared by Pearson's chi-squared test,
Timepoint [1] 327292 0
Until 2 months after vaccination,
Secondary outcome [2] 327371 0
To compare the prevalence of serogroup-specific meningococcal carriage among Hajj pilgrims receiving quadrivalent meningococcal conjugate vaccine to that in those receiving quadrivalent meningococcal polysaccharide vaccine 6-11 months after immunisation.


Pharyngeal swabs will be obtained from the participants for microbiological testing. The rates of pharyngeal carriage of meningococcci in both study arms will be compared by Pearson's chi-squared test in order to determine if the prevalence of serogroup-specific meningococcal carriage in Hajj pilgrims receiving quadrivalent meningococcal conjugate vaccine is different from that in pilgrims receiving quadrivalent meningococcal polysaccharide vaccine 6-11 months after vaccination.
Timepoint [2] 327371 0
6-11 months after the vaccination. The participants will be reached as soon as they are available 6 months after vaccination and can be swabbed till 11th month.
Secondary outcome [3] 327458 0
Comparison of adverse events related to vaccination between study arms.

All study participants will be given a hand-held paper diary or those who prefer so, a web-based diary to complete online with their iPhones over a period of one week following vaccination. In addition, participants will be actively followed up with a telephone call to enquire about any adverse reactions (e.g. systemic side effects: fever, myalgia, lethargy/fatigue; local reactions: redness, pain, swelling, any other adverse events requiring medical attention) over the one week period following vaccination. All serious adverse events will be reported and managed according to the practice guidelines. Within 60 days after their return from Hajj, the participants will be enquired about their health including details of any illness particularly major ones requiring hospital admission. Additionally, their family physicians will be kept informed of their participation in the study and requested to report all visits and hospital admissions to the study team throughout the follow up period to identify any related adverse events, and breakthrough meningococcal disease.
The rates of adverse events in both vaccine arms will be compared by Pearson's chi-squared test in order to determine if the prevalence of adverse events in Hajj pilgrims receiving quadrivalent meningococcal conjugate vaccine is different from that in pilgrims receiving quadrivalent meningococcal polysaccharide vaccine.
Timepoint [3] 327458 0
Within sixty days after coming from Hajj

Eligibility
Key inclusion criteria
i) Any pilgrim planning to attend Hajj pilgrimage from the selected countries (Australia, Qatar and Saudi Arabia).
ii) Aged 18 years or older.
iii) Be able to provide informed consent.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
i) Persons who received a MenACWY-C vaccine anytime in the past or a MenACWY-PS in the last three years will be excluded
ii) Persons on long-term steroids or other immune suppressants or immunodeficiency conditions will be excluded.
iii) Persons with previous history of invasive meningococcal disease will be excluded.
iv) Individuals with a history of systemic antibiotic use during the previous 7 days will be temporarily excluded but could be included after a lapse of 7 days since the last day of antibiotic administration. Individuals who give a history of using antibiotics during Hajj (following recruitment) will be retained in trial. A delayed swab, a week after completing the antibiotic course, will be attempted, but if that is not practical, they will be excluded them from the ‘per-protocol’ analysis. Individuals who received a conjugate monovalent meningococcal vaccine (MenC or MenA) in the past can be included into the study, but will be excluded for MenC- or MenA-specific analyses, but will be included for analyses with respect to the other serogroups.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised sequence generation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Mean difference and 95% Confidence Interval (CI) between study groups will be calculated in the proportion of participants with documented pharyngeal carriage of groupable meningococci within sixty days after completion of Hajj (visit 2) for each serogroup contained within the vaccines.

Sample size per arm under a range of assumptions for prevalence of carriage in polysaccharide arm and a range of vaccine efficacy expectations (for the conjugate vaccine) is calculated. Conjugate meningococcal C vaccine is known to reduce carriage by at least 75% (Maiden et al. 2008); assuming 3% carriage (against any one serogroup) among Hajj pilgrims immunised with a polysaccharide vaccine, and a carriage rate of 0.75% in those receiving a conjugate vaccine a sample size of 567 per arm would be needed to achieve 80% power with 95% confidence level (2 sided alpha = 0.05) and 75% reduction in carriage in the conjugate vaccine arm compared to the polysaccharide vaccine arm.

Assuming that 20% of pilgrims will have received antibiotics at the Hajj and or a MenACWY-C in the past, and another 20% will be lost to follow-up, a total of 1780 pilgrims will be recruited for the study.

It is likely that pilgrims given the polysaccharide vaccine will not remain at the theoretical carriage rate of 3% but actually acquire carriage of meningococci during the Hajj, so that the measured colonisation rate in this arm may exceed 3% - as was demonstrated with pilgrims returning to Singapore after the 2001 Hajj and to Turkey after the 2010 Hajj (Ceyhan et al. 2013; Wilder-Smith et al. 2002). Hence this is a conservative power estimate and significant differences may well be shown with fewer participants.

In summary, over 2000 pilgrims will be screened from Muslim dominated areas of Australia, and major cities in Saudi Arabia to achieve a sample size of 1780 participants, of these 1400 will be recruited from Saudi Arabia, 200 from Australia and 180 from Qatar.


References:
Ceyhan M, Celik M, Demir ET, Gurbuz V, Aycan AE, Unal S. Acquisition of Meningococcal Serogroup W-135 Carriage in Turkish Hajj Pilgrims Who Had Received the Quadrivalent Meningococcal Polysaccharide Vaccine. Clin Vaccine Immunol. 2013;20(1):66-8.

Maiden MC, Ibarz-Pavon AB, Urwin R, Gray SJ, Andrews NJ, Clarke SC, et al. Impact of meningococcal serogroup C conjugate vaccines on carriage and herd immunity. J Infect Dis. 2008;197(5):737-43.

Wilder-Smith A, Barkham TM, Earnest A, Paton NI. Acquisition of W135 meningococcal carriage in Hajj pilgrims and transmission to household contacts: prospective study. BMJ. 2002;325(7360):365-6.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC
Recruitment outside Australia
Country [1] 8152 0
Saudi Arabia
State/province [1] 8152 0
Country [2] 8153 0
Qatar
State/province [2] 8153 0

Funding & Sponsors
Funding source category [1] 294425 0
Charities/Societies/Foundations
Name [1] 294425 0
Qatar National Research Fund (QNRF)
Address [1] 294425 0
Qatar National Research Fund, PO Box 5825, Doha
Country [1] 294425 0
Qatar
Funding source category [2] 304309 0
Charities/Societies/Foundations
Name [2] 304309 0
Salem bin Mahfouz Foundation
Address [2] 304309 0
Red Sea Mall, King Abdulaziz Rd, Ash Shati, Jeddah 21146
Country [2] 304309 0
Saudi Arabia
Primary sponsor type
Hospital
Name
National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases (NCIRS), The Children's Hospital at Westmead
Address
The Children's Hospital at Westmead, Cnr Hawkesbury Rd and Hainsworth St, Westmead, Locked Bag 4001, Westmead NSW 2145, Australia
Country
Australia
Secondary sponsor category [1] 293277 0
University
Name [1] 293277 0
The University of Sydney
Address [1] 293277 0
The University of Sydney, NSW 2006
Country [1] 293277 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295851 0
Human Research Ethics Committee, The University of Sydney
Ethics committee address [1] 295851 0
Office of Research Integrity
Research Portfolio
Margaret Telfer Building (K07)
71-79 Arundel Street
Forest Lodge
NSW 2006
Ethics committee country [1] 295851 0
Australia
Date submitted for ethics approval [1] 295851 0
10/08/2015
Approval date [1] 295851 0
04/01/2016
Ethics approval number [1] 295851 0
2015/693
Ethics committee name [2] 295853 0
Sydney Children's Hospitals Network Human Research Ethics Committee
Ethics committee address [2] 295853 0
Research Ethics Office
Corner Hawkesbury Road
and Hainsworth Street
Locked Bag 4001
Westmead NSW 2145
Sydney Australia
DX 8213 Parramatta
Ethics committee country [2] 295853 0
Australia
Date submitted for ethics approval [2] 295853 0
27/05/2016
Approval date [2] 295853 0
01/06/2016
Ethics approval number [2] 295853 0
HREC/16/SCHN/209

Summary
Brief summary
Intense congestion, including shared accommodation and compromised hygiene, during mass events such as Hajj pilgrimage amplify the risk of invasive meningococcal disease. Intercontinental spread of serogroup A meningococcal disease in 1987 and serogroup W135 disease in 2000 and 2001 affected thousands of Hajj pilgrims globally. Quadrivalent meningococcal polysaccharide (serogroups A, C, W135 and Y) vaccine was able to bring these epidemics under control, but the vaccine is not effective at reducing pharyngeal carriage of meningococci. A conjugate vaccine can reduce long term meningococcal carriage; for example, the quadrivalent conjugate vaccine has been shown to reduce carriage over 12 months from vaccination in adults aged 18-24 years old. However, the impact of conjugate meningococcal vaccines on meningococcal carriage status among Hajj pilgrims, most of whom are older than 24 years, is not known.
We, therefore, believe that a well-powered carriage study in Hajj pilgrims is an urgent need. During the Hajj 2017, we plan to conduct a single-blinded, randomised, controlled trial of quadrivalent meningococcal conjugate vaccine for head-to-head comparison with quadrivalent polysaccharide among pilgrims from Australia, Qatar and Saudi Arabia.
Pilgrims from participating countries, planning to attend Hajj in Makkah in 2017 will be randomised to receive either a ‘conjugate vaccine’ or a ‘polysaccharide vaccine’. Following informed consent, pharyngeal swabs will be collected from pilgrims in both arms a few months before their travel to Hajj. The participants will then receive their respective vaccines (observers will remain blind to this selection), a second set of pharyngeal swabs will be collected within sixty days after completion Hajj, preferably within 7 days and a third set of pharyngeal swabs will be collected at 6 to 11 months.
Pharyngeal swabs will be processed by standard culture methods to detect meningococcal carriage; isolates will be characterised by serogroup, subtype, serosubtype, and sequence type. The pharyngeal swabs will also be tested for any antimicrobial resistance elements present. Data will be anonymised and analysed for the following end points: a) comparison between the study arms with respect to pharyngeal carriage rates of meningococci after return from Hajj, b) change in pharyngeal carriage rates of meningococci from before to a few months after vaccination, and c) comparison of long term carriage rates at 6 to 11 months after vaccination between study arms, and d) comparison of adverse events related to vaccination between study arms. This research could inform renewed policy on meningococcal vaccination for Hajj pilgrims as well as for attendees of other large events.

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 68694 0
Dr Harunor Rashid
Address 68694 0
National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases (NCIRS), The Children's Hospital at Westmead, Cnr Hawkesbury Rd and Hainsworth St, Westmead, Locked Bag 4001, Westmead NSW 2145
Country 68694 0
Australia
Phone 68694 0
+61 29845 1489
Fax 68694 0
+61 29845 1418
Email 68694 0
harunor.rashid@health.nsw.gov.au
Contact person for public queries
Name 68695 0
Dr Almamoon Mohammad Omar Badahdah
Address 68695 0
National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases (NCIRS), The Children's Hospital at Westmead, Cnr Hawkesbury Rd and Hainsworth St, Westmead, Locked Bag 4001, Westmead NSW 2145
Country 68695 0
Australia
Phone 68695 0
+61 298451433
Fax 68695 0
+61 298451418
Email 68695 0
Almamoon.Badahdah@health.nsw.gov.au
Contact person for scientific queries
Name 68696 0
Dr Harunor Rashid
Address 68696 0
National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases (NCIRS), The Children's Hospital at Westmead, Cnr Hawkesbury Rd and Hainsworth St, Westmead, Locked Bag 4001, Westmead NSW 2145
Country 68696 0
Australia
Phone 68696 0
+61 29845 1489
Fax 68696 0
+61 29845 1418
Email 68696 0
harunor.rashid@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary