Clinical Trial Results:
Alemtuzumab and rheumatoid arthritis - an immunisation study
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Summary
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EudraCT number |
2010-021146-22 |
Trial protocol |
GB |
Global end of trial date |
20 Nov 2014
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Results information
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Results version number |
v2(current) |
This version publication date |
28 Sep 2016
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First version publication date |
29 Jul 2016
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Other versions |
v1 |
Version creation reason |
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Summary report(s) |
Alemtuzumab EudraCT 2010-021146-22 Abstract of study and data |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
5339
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Newcastle upon Tyne Hospitals NHS Foundation Trust, Joint Research Office
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Sponsor organisation address |
Regent Point (Level 1), Gosforth, Newcastle upon Tyne, United Kingdom, NE3 3HD
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Public contact |
Professor John Isaacs, Institute of Cellular Medicine, Musculoskeletal Research Group, Newcastle University, 0191 222 5337, j.d.isaacs@ncl.ac.uk
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Scientific contact |
Professor John Isaacs, Institute of Cellular Medicine, Musculoskeletal Research Group, Newcastle University, 0191 222 5337, j.d.isaacs@ncl.ac.uk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
16 Nov 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
20 Nov 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
20 Nov 2014
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To compare the ability to mount immune responses (to measure the function of the immune system) in patients who received alemtuzumab for rheumatoid arthritis between 1991 and 1994 and a matched control group with long-standing rheumatoid arthritis. The control group will be matched for disease duration (within 5 years of matched case), age (within 10 years of matched case) and gender.
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Protection of trial subjects |
Potential participants will have the study explained to them and be given ample time to ask questions and consider participation prior to obtaining written informed consent.
All study procedures performed by qualified and trained study staff
All AEs/SAEs recorded by site staff during study participation.
Trial Management Group to meet at regular intervals to discuss any study issues, especially information relevant to participant safety or welfare
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Background therapy |
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Evidence for comparator |
Patients receiving alemtuzumab for RA between 1991 and 1994 have remained lymphopenic during long-term follow-up but do not appear otherwise to be immunosuppressed. An observational study is performed approximately every 5 years on these patients, documenting mortality against a closely matched cohort of patients with RA who have never received alemtuzumab. This has confirmed no excess in mortality over 12 years follow-up to date. There were no specific control subjects in the original alemtuzumab studies but mortality has been compared with a closely matched control group of patients from the EULAR database. However, the latter database does not provide morbidity outcomes for comparison. A recent immunization study looked at serological responses to vaccines in alemtuzumab recipients but, due to restrictions within the study, it was not possible to compare responses with matched controls. The current study seeks to rectify that evidence gap. | ||
Actual start date of recruitment |
01 Oct 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 17
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Worldwide total number of subjects |
17
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EEA total number of subjects |
17
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
8
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From 65 to 84 years |
9
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients that were treated with alemtuzumab between 1991 and 1994 were identified by the Chief Investigator from the previous study database. Matched-control patients who had not received alemtuzumab, were identified locally in Addenbrookes Hospital, Cambridge, UK. All participants were recruited between October 2013 and October 2014. | |||||||||
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Pre-assignment
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Screening details |
Inclusion criteriafor for the study were as follows Alemtuzumab recipients -Received alemtuzumab in original Cambridge studies (1991-94) Matched controls - Rheumatoid arthritis according to 1987 ACR criteria, Disease duration within 5 years of matched case, Age within 10 years of matched case, Gender profile to match alemtuzumab recipients | |||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | |||||||||
Blinding implementation details |
n/a
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Alemtuzumab cohort | |||||||||
Arm description |
Patients that were treated with alemtuzumab (CAMPATH-1H) for RA between 1991 and 1994 | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Alemtuzumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion in administration system
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Routes of administration |
Intravenous drip use
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Dosage and administration details |
Alemtuzumab administered previously to the Alemtuzumab cohort during 1991-1994 study, not administered in the current study
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Arm title
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Control | |||||||||
Arm description |
Age and sex matched RA patients with a similar disease duration, who had not received alemtuzumab | |||||||||
Arm type |
Experimental matched control | |||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
Alemtuzumab cohort
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Reporting group description |
Patients that were treated with alemtuzumab (CAMPATH-1H) for RA between 1991 and 1994 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Control
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Reporting group description |
Age and sex matched RA patients with a similar disease duration, who had not received alemtuzumab | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Alemtuzumab cohort
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Reporting group description |
Patients that were treated with alemtuzumab (CAMPATH-1H) for RA between 1991 and 1994 | ||
Reporting group title |
Control
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Reporting group description |
Age and sex matched RA patients with a similar disease duration, who had not received alemtuzumab | ||
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End point title |
Seroconversion rate [1] | |||||||||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Overall trial
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Vaccine data not result of statistical tests |
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End point title |
Seroprotection rate [2] | |||||||||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Overall trial
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Vaccine data not result of statistical tests |
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||
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End point title |
% Satisfactory response [3] | |||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Overall trial
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Vaccine data not result of statistical tests |
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| No statistical analyses for this end point | ||||||||||||||||
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End point title |
Seroprotection rate [4] | |||||||||||||||||||||
End point description |
Including patients who had influenza vaccine out with this study period.
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End point type |
Primary
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End point timeframe |
Overall trial
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Vaccine data not result of statistical tests |
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Seroconversion rate [5] | |||||||||||||||||||||
End point description |
Patients vaccinated at interview
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End point type |
Primary
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End point timeframe |
Overall trial
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| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Vaccine data not result of statistical tests |
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Seroprotection rate [6] | |||||||||||||||||||||
End point description |
Patients vaccinated at interview
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End point type |
Primary
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End point timeframe |
Overall trial
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| Notes [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Vaccine data not result of statistical tests |
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| No statistical analyses for this end point | ||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Overall study participation
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
As reported | |||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
0
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Reporting groups
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Reporting group title |
Alemtuzumab cohort
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Reporting group description |
Patients that were treated with alemtuzumab (CAMPATH-1H) for RA between 1991 and 1994 | |||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Control
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Reporting group description |
Age and sex matched RA patients with a similar disease duration, who had not received alemtuzumab | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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21 Sep 2012 |
• Re-classification of IMP by MHRA. MHRA now define the alemtuzumab (administered to the alemtuzumab recipients at Cambridge between 1991 and 1994) as the IMP for this study. The seasonal flu, pneumonia and diptheria, polio and tetanus booster vaccines to be administered within the context of this study are now NIMPs (physiological probes).
• The Pharmacovigilance section of the protocol is substantially altered to reflect the IMP & NIMP definitions. The time elapsed since last administration of IMP is also referenced (stipulating that adverse reactions to the IMP, or SUSARs linked to an interaction between the IMP and NIMP are NOT anticipated) . Pregnancy information for female partners of male participants will also now be collected only for the alemtuzumab group (who were originally administered the IMP).
• Streamline participant follow-up and the time points I assessments as per the primary and secondary outcome measures; also amended are the time points stipulated in the definition of end of study and the time points for collecting AEs/SAEs.
• Reduction in the total volume of blood required at the screening and follow up visit.
• SmPC documentation is updated to incorporate the re-classification of the IMP, change of flu vaccine brand routinely available at Addenbrooke's Hospital in 2012- 2013 and an update to Pneumovax II SmPC.
• Logistics to now allow the screening and baseline visit to be combined into one single clinic visit (with the exception of female participants of child bearing potential, where results from the study-specific serum pregnancy test are required prior to vaccination) .
• Protocol section 11 is substantially reworded, primarily to reflect that the ONS data (for alemtuzumab recipients) as received by the Chief Investigator does not contain patient contact details (as was previously perceived).
• Amendments to study documentation in line with the changes outlined in protocol
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18 Jul 2013 |
SmPC documentation updated
The process outlined for identification, screening and recruitment of alemtuzumab participants (protocol section 11.1) has been amended/further clarification provided.
Exclusion criteria amended for control patients to exclude patients who received rituximab within the past 6 months (extended from 3 months, as per previous study protocol)
Exclusion criteria amended for control patients to exclude females who are known to be pregnant or breast feeding
Reduction in total volume of blood required for analysis, following latest confirmation from labs.
Following Sponsor confirmation, statistical input to the Trial Oversight Committee is not deemed necessary. The Independent Chair and Independent Assessor for safety/adverse events are now appointed.
The format/layout of the DAS28 (incorporated as protocol Appendix E) has been amended.
Minor changes to study documentation, including change to contact details/name of central labs, blood volume inconsistency within protocol, etc. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| We acknowledge that due to the small numbers in both groups robust statistical comparison was not possible. Additionally, the timing of vaccination outwith this study was unknown potentially making meaningful comparison difficult | |||
