Phenotyping Seroconversion Following Vaccination Against COVID-19 in Patients on Haemodialysis Study
Conditions: End Stage Kidney Disease
Sponsor: University of Leicester

 
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PHENOTYPING SEROCONVERSION FOLLOWING VACCINATION AGAINST COVID-19  
IN PATIENTS ON HAEMODIALYSIS 
Sponsor Reference No:  
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Chief Investigator: 
Dr Matthew Graham-Brown – NIHR Academic Clinical Lecturer in 
Renal medicine, Department of Cardiovascular Sciences, 
University of Leicester, and Honorary Specialist Registrar Renal 
Medicine, John Walls Renal Unit, University Hospitals Leicester.  
Investigators:  
Professor Nigel Brunskill  
Dr Richard Baines 
Professor James Burton 
Dr Rupert Major 
Dr Haresh Selvaskanden 
Dr Katherine Hull 
Miss Rosey Billany 
Dr Sherna Adenwalla 
Sponsor:  
University of Leicester 
Funder: 
Leicester Charity Hospitals 
Signatures:  
The approved protocol should be signed by author(s) and/or 
person(s) authorised to sign the protocol 
 
Confidentiality Statement 
All information contained within this protocol is regarded as, and must be kept confidential.  No part 
of it may be disclosed by any Receiving Party to any Third Party, at any time, or in any form without 
the express written permission from the Chief Author/Investigator and / or Sponsor. 

 
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Authors 
 
List here all authors / collaborators that have assisted with the writing of the protocol 
 
Dr Matthew Graham-Brown 
Professor Nigel Brunskill 
Professor James Burton 
Dr Rupert Major 
Dr Haresh Selvaskanden 
Dr Katherine Hull 
Miss Rosey Billany 
Dr Sherna Adenalla 

 
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Signature Page 
 
Chief Investigator Name: 
Dr Matthew Graham-Brown 
Chief Investigator signature: 
_________________________________ 
Date: 06/05/2022 
  
 
Sponsor Representative Name: 
__Yasmin Godhania__ 
Sponsor Representative signature: 
 
Date: 
06/05/2022 
  
 
Principal Investigator Name: Dr Matthew Graham-Brown 
Principal Investigator signature: ________________________________ 
Date: 
06/05/2022 
  
(In cases of Multi-centre studies, this must be replicated for each site) 
 
 

 
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TABLE OF CONTENTS 
1. 
AMENDMENT HISTORY ......................................................................................................... 5 
2. 
SYNOPSIS .............................................................................................................................. 6 
3. 
ABBREVIATIONS .................................................................................................................... 7 
4. 
BACKGROUND AND RATIONALE ......................................................................................... 8 
5. 
OBJECTIVES .......................................................................................................................... 9 
6. 
STUDY DESIGN .................................................................................................................... 10 
7. 
TRIAL PARTICIPANTS ......................................................................................................... 12 
8. 
STUDY PROCEDURES ........................................................................................................ 13 
9.  TREATMENT OF TRIAL PARTICIPANTS ............................................................................... 18 
10. SAFETY REPORTING .......................................................................................................... 19 
11. STATISTICS .......................................................................................................................... 21 
12. DIRECT ACCESS TO SOURCE DATA/DOCUMENTS.......................................................... 22 
13. QUALITY CONTROL AND QUALITY ASSURANCE PROCEDURES.................................... 23 
14. CODES OF PRACTICE AND REGULATIONS ...................................................................... 24 
15.  DATA HANDLING AND RECORD KEEPING ........................................................................ 25 
16. STUDY GOVERNANCE ........................................................................................................ 26 
17.     FINANCING AND INSURANCE .......................................................................................... 27 
18. PUBLICATION POLICY ......................................................................................................... 28 
19. REFERENCES ...................................................................................................................... 29 
20. Study Visit Table .................................................................................................................... 30 
 
 
 

 
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1. 
AMENDMENT HISTORY 
Amendment 
No. 
Protocol 
Version 
No. 
Date 
issued 
Author(s) of changes 
Details of Changes made 
Pre-approval  
2 
22.01.2021 
Miss 
R 
Billany 
Dr M Graham-Brown 
1. Samples will now be taken 1 
month after the first vaccine 
dose and 1 month after the 
second vaccine dose 
SA01 
2 
 
Miss R Billany 
Dr M Graham- Brown 
These changes were made at the same 
time as the response to REC above: 
 
1. Addition of a baseline sample 
and a 6 month post second 
vaccine dose sample 
2. Access to stored clinical 
samples for patients (to 
prevent having to take the 
baseline sample) 
3. An increase in the amount of 
blood taken at each timepoint  
4. Analysis and storage of 
samples at University of 
Leicester  
5. Transfer of samples to the 
CRICK Institute 
SA02 
3 
19.02.2021 
Miss R Billany 
1. Addition of a survey pack for 
patients and controls  
SA03 
4 
16/08/2021 
Miss R Billany 
Dr M Graham- Brown 
1. Addition of additional time 
points for blood sampling, 
including before and following 
any subsequent booster doses. 
2. Addition of the ability to 
transfer samples collaborating 
centres for analyses that 
cannot be completed in 
Leicester under the terms of 
material transfer agreements 
agreed between UoL and 
collaborating centres,  
3. Extend the study time period 
for a further 24 months to allow 
us to collect the additional 
blood samples above 
NSA01 
4.1 
03/05/2022 
Miss R Billany 
1. Reduction of the sample size to 115 

 
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2. 
SYNOPSIS 
 
Study Title 
PHENOTYPING SEROCONVERSION FOLLOWING VACCINATION 
AGAINST COVID-19 IN PATIENTS ON HAEMODIALYSIS 
Internal ref. no. 
0810 
Trial Design 
Prospective observational 
Trial Participants 
End Stage Kidney Disease on Haemodialysis and Healthy volunteers 
Planned Sample Size 
95 patients with end stage kidney disease on haemodialysis and 20 
healthy volunteers  
Planned Trial Period 
3 years (36 months) 
Primary Objective 
• 
To phenotype the 1 month  seroconversion following the first 
vaccination dose and the 1 month and 6 month seroconversion 
following the second vaccination dose against COVID-19 in 
haemodialysis patients 
Secondary 
Objectives 
• 
To compare rates of 1 month  seroconversion following the first 
vaccination dose and the 1 month and 6 month seroconversion 
following the second vaccination dose against COVID-19 
between patients on maintenance haemodialysis and healthy 
control volunteers 
• 
To assess antibody levels 12, 18 and 24 months post second 
vaccination. 
• 
Assess the antibody response before and 1 month after any 
booster vaccinations  

 
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3. 
ABBREVIATIONS 
AE 
Adverse event 
AR  
Adverse reaction 
CI 
Chief Investigator 
CKD 
Chronic Kidney Disease 
CRO  
Contract Research Organisation 
EC 
 
Ethics Committee (see REC) 
eGFR 
Estimated Glomerular Filtration Rate 
ESKD 
End Stage Kidney Disease 
GCP 
Good Clinical Practice 
GP 
General Practitioner 
ICF 
Informed Consent Form 
 
NHS 
National Health Service 
NRES 
National Research Ethics Service  
PI 
Principal Investigator 
PIL/S 
Participant/ Patient Information Leaflet/Sheet 
R&D / R&I 
NHS Trust Research &Development / Innovation Department 
REC 
Research Ethics Committee 
SAE 
Serious Adverse Event 
SAR 
Serious Adverse Reaction 
TMF 
Trial Master File 
 

 
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4. 
BACKGROUND AND RATIONALE 
Patients with end stage kidney disease (ESKD) on haemodialysis are more likely to suffer poorer outcomes 
following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (1). This is 
likely to be because these patients have higher levels of co-morbid diseases and they are relatively 
immunosuppressed due to the effects of advanced kidney disease. The humoral response against common 
viral vaccination is known to be blunted in patients with ESKD (2) and there are data to suggest 
seroconversion following infection with COVID-19 is blunted in patients with kidney disease (3). A successful 
programme of vaccination will undoubtedly improve outcomes for patients on haemodialysis, but vaccine 
testing programmes have not included patients  with ESKD. Whilst initial press-coverage of the efficacy of 
vaccines which are  available for use is promising, they are untested in patients on haemodialysis who are 
known to be relatively immunosuppressed as a result of their renal disease and as such the efficacy for this 
patient group is not known. 
This study will phenotype the IgG antibody response to vaccination for COVID-19 in 95 patients on 
haemodialysis compared to 20 healthy volunteers. Antibody testing will be conducted at 1 month post first 
vaccination dose and 1 month and 6 months post second vaccination dose. This will give crucial information 
as to the efficacy of the vaccine and inform possible requirements for re-vaccination. 
  

 
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5. 
OBJECTIVES 
This study will: 
1. Phenotype the 1 month  IgG antibody response to the first vaccination dose and the 1 
month and 6 month response to the second vaccination dose for COVID-19 in patients on 
haemodialysis 
2. Compare the 1 month IgG antibody response to the first vaccination dose and the 1 month 
and 6 month response to the second vaccination dose for COVID-19 between patients on 
haemodialysis and healthy volunteers 
3. Assess the antibody response immediately before and 1 month after any booster 
vaccinations  
4. Measure antibody levels 12, 18 and 24 months after their second  vaccination 
 
 
 
 
 
 

 
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6. 
STUDY DESIGN 
 
6.1 Summary of study design 
This will be a prospective observational study. Following vaccination as part of the National 
COVID-19 vaccination programme, consecutive patients on haemodialysis (n=95) and healthy 
volunteers (n=20, NHS workers who are likely to be vaccinated in the first wave of vaccination) 
will attend for IgG antibody testing to COVID-19 1 month after the first dose and 1 month and 6 
months after the second dose of vaccine. Antibody tests will also be done immediately before 
and 1 month after any booster vaccination and 12, 18 and 24 months after second  vaccination 
dose. 
 
6.2 Outcome measures: 
IgG seroconversion at 1 month after the first dose and 1 month and 6 months after the second 
dose of vaccine.  
Antibody levels immediately before and 1 month after any booster vaccination and 12, 18 
and 24 months after second  vaccination. 
A survey pack containing: Section 1: General Practice Physical Activity Questionnaire 
(GPPAQ), Section 2: PROMIS Global Health Scale, Section 3: Pittsburgh Sleep Quality Index 
(PSQI) 
 
Details of outcome measures are discussed below: 
Participants with ESKD on haemodialysis will have blood sampling 1 month following the first 
vaccination dose and 1 month and 6 months following the second vaccination dose when they attend 
for their regular haemodialysis slot on the dialysis unit. Additionally, blood will be sampled in the 
same way from haemodialysis patients immediately before and 1 month after any booster doses of 
the vaccine and 12 months, 18 months and 24 months after second vaccination dose. Serum 
samples from all participants will be tested for the presence of spike protein antibodies using the 
Siemens Centaur platform currently used at the University Hospitals of Leicester NHS Trust. In order 
to obtain a baseline sample we will access routinely stored clinical samples to prevent the need for 
additional samples to be taken.  

 
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Participants who are healthy volunteers will attend the blood room at the Leicester General Hospital 
for samples to be taken at baseline, after the first vaccination dose and 1 month and 6 months 
following the second vaccination dose. Additionally, blood will be sampled in the same way for 
healthy volunteers immediately before and 1 months after any booster doses of the vaccine and 12 
months, 18 months and 24 months after second  vaccination dose. 
Participants recruited to the study will be contacted via telephone to collect relevant details of 
medical history and demographics and their medical records will be accessed to collect recent blood 
test results and historic tests results for COVID-19 (both antigen and antibody tests). 
 
 
 
 
 

 
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7. 
TRIAL PARTICIPANTS 
7.1 
Overall Description of Trial Participants 
95 prevalent patients on maintenance haemodialysis and 20 healthy volunteers will be recruited 
following vaccination for COVID-19.  
7.2 
Inclusion/Exclusion Criteria (ESKD patients on haemodialysis) 
Inclusion Criteria 
• Age>18 years 
• ESKD on maintenance haemodialysis 
• Able and willing to give informed consent 
• Have completed or due to complete vaccination against COVID-19 
Exclusion Criteria 
• Acute kidney injury requiring temporary haemodialysis  
• Unable to give informed consent 
• Pregnancy 
7.3 
Healthy Controls Inclusion/Exclusion criteria 
Inclusion Criteria  
• Age>18 years 
• Able and willing to give informed consent# 
• Have completed or due to complete vaccination against COVID-19 
Exclusion Criteria 
• History of immunosuppression  
• Use of immunosuppressive medications in prior 12 months 
• Known history of chronic kidney disease 
• Pregnancy 
 

 
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8. 
STUDY PROCEDURES 
Patients on haemodialysis are currently being vaccinated by invitation in secondary care. As part of routine 
clinical care, patients are being asked when they attend dialysis whether they have been called for 
vaccination or whether they have been vaccinated. When they have been vaccinated this is routinely 
recorded by the clinical staff on the University of Leicester renal database (PROTON). The clinical team will 
identify people who have been vaccinated through this database and members of the study team (who will 
also be members of the clinical team) will approach the patients to discuss the study and to give them a PIS 
should they want to take part. These patients will be followed up at their next dialysis session and if they wish 
to participate will be consented by a member of the research team. 
Healthy volunteers will be identified as members of the clinical team who are having the vaccine or those 
who contact the study team directly in response to posters advertising the study to healthy volunteers. Once 
healthy volunteers have been identified in these ways they will be given a PIS by a member of the study team 
and contacted after 48 hours by a member of the study team. If they wish to take part  they will then be 
consented by a member of the study team. 
 
8.1 
Informed Consent 
In both cases, participants will have a minimum of 48 hours to consider the patient information 
sheet, and the opportunity to question the study team, or other independent parties to decide 
whether they will participate in the study. 
Written informed consent will then be obtained by means of participant dated signature and 
dated signature of the person who presented and obtained the informed consent. The person 
who obtained the consent will be suitably qualified and experienced, and have been 
authorised to do so by the Chief/Principal Investigator as detailed on the Delegation of 
Authority and Signature log for the study. The original signed form will be retained at the study 
site within the Trial Master File (TMF) or Investigator Site File (ISF). A copy of the signed 
informed consent will be given to participants (or emailed to participants at their request) and 
a copy retained in the participant medical notes. Written informed consent will be taken prior 
to any assessments. 
8.2 
Screening and Eligibility Assessment 
Potential participants who are patients on haemodialysis will be screened prior to initial 
telephone contact by a member of the clinical team involved in patient care based on the 

 
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inclusion/exclusion criteria against patients. The clinical team will also screen clinic lists and 
the COVID-19 vaccination log on PROTON (see above) to identify and approach potential 
participants at routine dialysis sessions. 
Potential participants who are healthy volunteers will be NHS workers at the University 
Hospital of Leicester. It is anticipated that NHS workers will be amongst the first groups of 
people to receive the vaccine and these people will be made aware of the study through local 
poster advertisements in the department of renal medicine at the University Hospitals. Those 
interested in participating will be asked to contact the study team via email and the study 
team will then make contact to screen for eligibility, send the PIS and invite to take part as 
required. 
8.3 
Assessments 
For patients on haemodialysis, blood sampling for IgG antibody response to COVID-19 
vaccination will take place when the patient attends a routine dialysis appointment 1 month 
post first vaccination dose and 1 month and 6 months post second vaccination dose (3 
samples total). A baseline sample will be obtained from routinely stored clinical samples. 
Blood will be taken during the patients dialysis at the same time as bloods for routine clinical 
care with no additional procedures needed when blood is taken. Vaccines currently available 
or soon to be available require 2 doses before immunity is achieved and the blood antibody 
tests will be taken 1 month after the first  immunisation has been administered and 1 month 
and 6 months after the second. Blood will be taken from the arterial dialysis line at the start 
of dialysis so no additional venepuncture is required and no additional visits to a clinical 
environment are required.  
Healthy volunteers will be working in a clinical environment within UHL and will have their 
blood taken by a trained member of the research team (all of whom are working on the clinical 
service at UHL) at baseline, 1 month post the first vaccination dose and 1 month and 6 
months after the second vaccination dose. This will be arranged in the most practical way 
and will conform to Hospital protocols on the wearing of personal protective equipment in the 
clinical environment the blood is taken.  
Some of each sample will be processed in the laboratories at the University Hospitals of 
Leicester, and some will be processed and stored at the University of Leicester. One aliquot 

 
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of the stored samples will be transferred in accordance with a Material Transfer Agreement 
to the Francis Crick Institute (London). 
Clinical Information 
With the participant’s consent, the researcher team will access their clinical records and 
extract relevant medical and demographic information including:  
• Age 
• Gender 
• Ethnicity 
• Primary cause of renal failure 
• Previous history of transplantation 
• Time on dialysis  
• Co-morbidities 
• Blood test results 
• Medication 
• Smoking Habits 
• The specific vaccine administered (make/type) 
Past medical history, patient demographics, medications and relevant test results will be 
recorded for healthy volunteers in the same way through access of medical records. 
All information will be entered into a case report form (CRFs) which will be stored in a locked 
filing cabinet in the locked office of the Chief Investigator at the Leicester General Hospital. 
Data will be extracted from the CRF and entered into an excel spreadsheet that is  a coded 
and anonymised with no patient information which is stored on the UHL CardioRenal 
Research drive on NHS servers only accessible by members of the research team with 
specific access.  
Laboratory Tests 
30 ml (2 tablespoons) of venous blood samples will be taken from the arm by a trained 
member of the research team/clinical phlebotomy service at 1 month after the first vaccination 
dose and 1 month and 6 months after the second vaccination dose and using the Monovette 
System. A baseline sample will also be taken from healthy controls (the patient baseline 
sample will be extracted from routinely stored clinical samples).  

 
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Blood samples from each participant will be sent to the pathology labs for analysis and will 
be destroyed after the test is completed by the UHL pathology staff.  
Additional serum will be separated and stored in aliquots at -80°C at the University of 
Leicester (Maurice Shock Building, Level 1 Renal Research Laboratory).  
One aliquot per time point of the stored samples will be transferred in accordance with the 
details of a Material Transfer Agreement to the Francis Crick Institute (London) for further 
antibody analysis. Routinely stored clinical samples for patients (baseline) will also be 
transferred to the Francis Crick Institute. Any aliquots that have been transferred to the 
Francis Crick Institute will be disposed of after analysis is completed not stored or transferred 
back to the University of Leicester. 
Aliquots of stored samples will be transferred to additional collaborating sites with ethical 
approval to conduct analyses that cannot be completed locally in accordance with details of 
the Material Transfer Agreements drawn up between the University of Leicester and the 
collaborating centre. Any samples that are transferred externally will be disposed of after 
analysis is complete, not transferred back to the University of Leicester. 
Questionnaires 
A short survey pack will be administered at the point of consent containing the following: This 
will take less than 5 minutes to complete. 
Section 1: General Practice Physical Activity Questionnaire (GPPAQ) 
Section 2: PROMIS Global Health Scale 
Section 3: Pittsburgh Sleep Quality Index (PSQI) 
 
8.4 
Definition of End of Trial 
National Research Ethics Service (NRES)/Health Research Authority (HRA) standard 
operating procedures advise that the end of the research should be defined in relation to the 
collection of all data required to answer the research questions in the protocol. In the current 
study, this will be once all outcome measures have been analysed.  
8.5 
Discontinuation/Withdrawal of Participants from Study Treatment 

 
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Each participant has the right to withdraw from the study at any time without giving a reason. 
In addition, the investigator may discontinue a participant from the study at any time if the 
investigator considers it necessary for any reason including:  
• Significant protocol deviation 
• Significant non-compliance with treatment regimen or study requirements 
• An adverse event which requires discontinuation of the study or results in inability to 
continue to comply with study procedures 
• Disease progression which requires discontinuation of the study or results in inability 
to continue to comply with study procedures 
• Consent withdrawn 
• Lost to follow up 
If the participant is withdrawn due to an adverse event, the investigator will arrange for follow-
up visits or telephone calls until the adverse event has resolved or stabilised.   
8.6 
Source Data 
Source documents are original documents, data, and records from which participants’ CRF 
data are obtained.  In this trial, these will include:  
• Hospital records (from which medical history and previous and concurrent 
medication may be summarised into the eCRF) 
• Questionnaire pack 
 
In this study the eCRF will be used as the source document to store data extracted from: 
• Clinical and demographic data 
• Clinical blood results 
• IgG Antibody results 
 
All documents will be stored safely in confidential conditions on the UHL Renal Research 
drive. On all study-specific documents, other than the signed consent, the participant will be 
referred to by the study participant number/code, not by name. 
 

 
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9.  TREATMENT OF TRIAL PARTICIPANTS 
9.1 
Description of Study Treatment  
As described in section 6 this is a prospective observational study 
9.2 
Storage of Study Equipment or Related apparatus 
No storage of equipment will be required for this study as blood taking will be done  
  
 

 
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10. 
SAFETY REPORTING 
10.1 
Definitions 
10.1.1 Adverse Event (AE) 
 
An AE or adverse experience is any untoward medical occurrence in a patient or clinical investigation 
participants, which does not necessarily have to have a causal relationship with this treatment. 
 
An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory 
finding), symptom or disease temporally associated with the study, whether or not considered related 
to the study. 
 
10.1.2 Adverse Reaction (AR) 
 
All untoward and unintended responses related to the study. 
All cases judged by either the reporting medically qualified professional or the sponsor as having a 
reasonable suspected causal relationship to the study qualify as adverse reactions.   
 
10.1.3 Severe Adverse Events 
 
To ensure no confusion or misunderstanding of the difference between the terms "serious" and 
"severe", which are not synonymous, the following note of clarification is provided: The term "severe" 
is often used to describe the intensity (severity) of a specific event (as in mild, moderate, or severe 
myocardial infarction); the event itself, however, may be of relatively minor medical significance (such 
as severe headache).  This is not the same as "serious," which is based on patient/event outcome or 
action criteria usually associated with events that pose a threat to a participant's life or functioning. 
Seriousness (not severity) serves as a guide for defining regulatory reporting obligations. 
 
10.1.4 Serious Adverse Event or Serious Adverse Reaction 
 
A serious adverse event or reaction is any untoward medical occurrence that at any dose: 
• Results in death, 
• Is life-threatening, 
NOTE: The term "life-threatening" in the definition of "serious" refers to an event in which the 
participant was at risk of death at the time of the event; it does not refer to an event which 
hypothetically might have caused death if it were more severe. 
• Requires inpatient hospitalisation or prolongation of existing hospitalisation, 
• Results in persistent or significant disability/incapacity, or 
• Is a congenital anomaly/birth defect. 
• Other important medical events* 
*Other events that may not result in death, are not life threatening, or do not require hospitalisation, 
may be considered a serious adverse event when, based upon appropriate medical judgement, the 
event may jeopardise the patient and may require medical or surgical intervention to prevent one of 
the outcomes listed above. 
 
10.1.5 Expected Serious Adverse Events/Reactions 
 
We do not expect any SAEs related to either study assessments. Any SAE (defined above) will be 
recorded and reported within 24 hours of knowing about the event (see below 10.3). We will only 
report SAEs that are a direct result of the study intervention or protocol.  
 

 
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10.1.6 Anticipated Adverse Events/Reactions 
We do not anticipate any adverse events/reactions related to study procedures 
 
10.1.6 Suspected Unexpected Serious Adverse Reactions 
 
A serious adverse reaction, the nature or severity of which is not consistent with the applicable product 
information.   
 
10.2 
Reporting Procedures for All Adverse Events 
All AEs occurring during the study observed by the investigator or reported by the participant, whether 
or not attributed to study, will be recorded in the site-file. The following information will be recorded: 
description, date of onset and end date, severity, assessment of relatedness to study, other suspect 
device and action taken. Follow-up information should be provided as necessary.  
 
AEs considered related to the study as judged by a medically qualified investigator or the sponsor will 
be followed until resolution or the event is considered stable. All related AEs that result in a 
participant’s withdrawal from the study or are present at the end of the study, should be followed up 
until a satisfactory resolution occurs. 
 
It will be left to the investigator’s clinical judgment whether or not an AE is of sufficient severity to 
require the participant’s removal from treatment (see section 7.7). A participant may also voluntarily 
withdraw from treatment due to what he or she perceives as an intolerable AE. If either of these 
occurs, the participant must undergo an end of study assessment and be given appropriate care 
under medical supervision until symptoms cease or the condition becomes stable. 
 
The severity of events will be assessed on the following scale:  1 = mild, 2 = moderate, 3 = severe. 
The relationship of AEs to the study will be assessed by a medically qualified investigator. Only AEs 
that are judged to be related to the study intervention or procedures will be reported to the Sponsor. 
 
10.3 
Reporting Procedures for Serious Adverse Events 
Any SAEs related to the study procedures will be reported to the Sponsor within one working day of 
discovery or notification of the event. The Sponsor will perform an initial check of the information and 
ensure that it is reviewed at the next R&I Management meeting.  SAEs that meet these criteria for 
reporting will be recorded on an SAE form and sent to the Sponsor using the appropriate reporting 
form with the contact details on there. Additional information received for a case (follow-up or 
corrections to the original case) needs to be detailed on a new SAE form which must be sent to the 
Sponsor using the appropriate reporting form and the contact details on there.  
 
The Sponsor will report all SUSARs to the Research Ethics Committee concerned. Fatal or life-
threatening SUSARs must be reported within 7 days and all other SUSARs within 15 days. The CI 
will inform all investigators concerned of relevant information about SUSARs that could adversely 
affect the safety of participants. 
 
In addition to the expedited reporting above, the CI shall submit once a year throughout the study or 
on request an Annual Report to the Ethics Committee which lists all SAEs / SUSARs that have 
occurred during the preceding 12 months. 

 
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11. 
STATISTICS 
11.1 
Description of Statistical Methods 
 
Quantitative Analysis: 
To investigate the differences between groups in rates of 1 month seroconversion post the first 
vaccination dose and 1 month and 6 months post the second vaccination dose we will use analysis 
of covariance, adjusting for relevant baseline differences between groups. Suitable omnibus tests will 
be used to evaluate differences within groups.  
Similar analysis will be performed to look at the association between physical activity levels, sleep 
and vaccine seroconversion rates.  
A Statistical Analysis Plan will be drafted prior to analysis of the data. Analysis will be conducted in 
line with the SAP.  
 
11.2 
The Number of Participants 
 
This study will include 115 participants. 95 patients with ESKD on haemodialysis and 20 healthy 
volunteers 
 
11.3 
The Level of Statistical Significance  
α= 0.05 
 
 
11.4 
Procedure for Accounting for Missing, Unused, and Spurious Data. 
Missing data will be handled by imputation of last variable carried forward (assumption of no change). 
 
11.5 
Procedures for Reporting any Deviation(s) from the Original Statistical Plan 
Any deviation(s) from the original statistical plan will be described and justified in the final report. 

 
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12. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
Direct access will be granted to authorised representatives from the sponsor, host institution and the 
regulatory authorities to permit trial-related monitoring, audits and inspections. Participants will be 
asked to consent for this to occur if required. 

 
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13. 
QUALITY CONTROL AND QUALITY ASSURANCE PROCEDURES 
The study will be conducted in accordance with the current approved protocol, ICH GCP, relevant 
regulations and standard operating procedures. Regular monitoring will be performed according to 
ICH GCP. Data will be evaluated for compliance with the protocol and accuracy in relation to source 
documents. Following written standard operating procedures, the monitors will verify that the clinical 
trial is conducted and data are generated, documented and reported in compliance with the protocol, 
GCP and the applicable regulatory requirements.  
 

 
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14. 
CODES OF PRACTICE AND REGULATIONS 
 
14.1 
Ethics 
Blood sampling - in this study we will collect 30mL of blood from each participant at each specified 
time point. This will be taken from dialysis lines for patients on haemodialysis and using venepuncture 
for healthy volunteers. As is always the case when using venepuncture, there is a small risk of pain 
and bruising. To minimise these risks venepuncture will be performed by a trained member of the 
research team. 
 
14.2 
Sponsor Standard Operating Procedures 
All relevant Sponsor SOPs will be followed to ensure that this study complies with all relevant 
legislation and guidelines  
 
14.3 
Declaration of Helsinki 
The Investigator will ensure that this study is conducted in full conformity with the current revision of 
the Declaration of Helsinki (last amended October 2000, with additional footnotes added 2002 and 
2004). 
 
14.4 
ICH Guidelines for Good Clinical Practice 
The Investigator will ensure that this study is conducted in full conformity with relevant regulations 
and with the ICH Guidelines for Good Clinical Practice (CPMP/ICH/135/95) July 1996. 
 
14.5 
Approvals  
Once Sponsor authorisation has been confirmed, the protocol, informed consent form, participant 
information sheet and any proposed advertising material will be submitted to an appropriate Research 
Ethics Committee (REC), regulatory authorities (MHRA in the UK), and host institution(s) for written 
approval. 
  
Once Sponsor authorisation has been confirmed, the Investigator will submit and, where necessary, 
obtain approval from the above parties for all substantial and non-substantial amendments to the 
original approved documents.    
 
14.6 
Participant Confidentiality 
The trial staff will ensure that the participants’ anonymity is maintained.  The participants will be 
identified only by initials and a participant’s ID number on the CRF and any electronic database.  All 
documents will be stored securely and only accessible by trial staff and authorised personnel. The 
study will comply with the Data Protection Act which requires data to be anonymised as soon as it is 
practical to do so.   

 
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15.  
DATA HANDLING AND RECORD KEEPING 
 
All study data will be entered into an SPSS database on a secure University of Leicester system. This 
database will only be assessable on password protected University of Leicester or UHL computers. 
The participants will be identified by a study specific participants number and/or code in this database.  
The name and any other identifying detail will NOT be included in any study data electronic file. 
Original identities will be kept in the trial site file, accessible only to researchers on the study. All 
documents containing source data will be kept in a locked office. 
 

 
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16. 
STUDY GOVERNANCE 
16.1 
Trial Steering Committee (TSC) 
 
The TSC consists of: Dr Matthew Graham-Brown, Professor Nigel Brunskill, Prof James Burton, Dr 
Rupert Major and Miss Roseanne Billany. The TSC will aim to meet every 3 months throughout the 
study to review progress and ensure results are disseminated appropriately and in a timely fashion. 
 

 
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17.     FINANCING AND INSURANCE 
 
Research Costs - the costs of the R&I itself that end when the research ends. They relate to activities 
that are being undertaken to answer the research questions. 
 
Research costs are being funded by Leicester Hospitals Charity 
Major outgoings from the study 
Costs of IgG Antibody tests - £9000 (£30 per test, 150 participants with 2 tests each) 
Printing and posting - £500 

 
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18. 
PUBLICATION POLICY 
Research outputs will be in line with the University of Leicester Publication policy 
(https://www2.le.ac.uk/offices/researchsupport/integrity/code-of-conduct/5-after-research/5-1-
publishing-outputs accessed 19/06/2019). 
The results of this study will be presented in abstract form at relevant scientific and medical 
conferences, and will be published in appropriate peer-reviewed journals. The Chief Investigator as 
custodian of the data will oversee preparation and submission of abstracts and journal articles, and 
his permission must be obtained prior to preparation of any reports including reference to the study, 
data or results. Authorship will include all individuals who have made significant contributions to study 
design and execution, data analysis and interpretation and manuscript preparation. Authors and order 
will be at the discretion of the Chief Investigator. Individuals who have had involvement in the study 
but made insufficient intellectual contribution for authorship will be acknowledged in manuscripts. All 
authors will be given ample opportunity to review and approve all abstracts and manuscripts before 
submission, and those acknowledged will be asked for approval of their inclusion before publication. 
  
If a collaborator fails to provide agreed and timely contributions to or review of an abstract or 
manuscript, the Chief Investigator reserves the right to alter the authorship order, or to remove an 
individual from the author list in order to meet deadlines and avoid delays in dissemination and 
publication. 
 
 
 
 
 

 
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19. 
REFERENCES 
1. Williamson EJ, Walker AJ, Bhaskaran K, Bacon S, Bates C, Morton CE, et al.: Factors associated with 
COVID-19-related death using OpenSAFELY. Nature 584: 430–436, 2020, In press doi:10.1038/s41586-
020-2521-4 pmid:32640463 
2. P. Martin and L. S. Friedman, “Chronic viral hepatitis and the management of chronic renal failure,” Kidney 
International, vol. 47, no. 5, pp. 1231–1241, 1995. 
3. Prendecki M, Clarke C, Gleeson S, Greathead L, Santos E, McLean A, Randell P, Moore LSP, Mughal N, 
Guckian M, Kelleher P, Mcadoo SP, Willicombe M. Detection of SARS-CoV-2 Antibodies in Kidney 
Transplant Recipients. J Am Soc Nephrol. 2020 Oct 29:ASN.2020081152. doi: 10.1681/ASN.2020081152. 
Epub ahead of print. PMID: 33122285. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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20. 
STUDY VISIT TABLE  
 
 
 
 
 
Visit Name  
Haemodialysis patients  
Healthy volunteers  
Baseline 
Extraction of routine clinical and 
demographic information and previous 
relevant investigation, including telephone 
call if required 
 
Extraction of baseline sample from stored 
clinical samples.  
Extraction of routine clinical and 
demographic information and previous 
relevant investigation, including 
telephone call if required 
 
 Attend UHL blood room for IgG 
antibody testing for COVID 
1 month post first vaccine dose 
visit 
Blood taken from arterial line at the start 
of dialysis when patient attends for regular 
dialysis session 
Attend UHL blood room for IgG 
antibody testing for COVID  
1 month post second vaccine 
dose  
Blood taken from arterial line at the start 
of dialysis when patient attends for regular 
dialysis session 
Attend UHL blood room for IgG 
antibody testing for COVID  
6 months post second vaccine 
dose 
Blood taken from arterial line at the start 
of dialysis when patient attends for regular 
dialysis session 
Attend UHL blood room for IgG 
antibody testing for COVID 
Immediately before any planned 
booster vaccine 
Blood taken from arterial line at the start 
of dialysis when patient attends for regular 
dialysis session 
Attend UHL blood room for IgG 
antibody testing for COVID 
1 month after any booster doses 
of COVID vaccine 
Blood taken from arterial line at the start 
of dialysis when patient attends for regular 
dialysis session 
Attend UHL blood room for IgG 
antibody testing for COVID 
12 months after second 
vaccination 
Blood taken from arterial line at the start 
of dialysis when patient attends for regular 
dialysis session 
Attend UHL blood room for IgG 
antibody testing for COVID 
18 months after second 
vaccination 
Blood taken from arterial line at the start 
of dialysis when patient attends for regular 
dialysis session 
Attend UHL blood room for IgG 
antibody testing for COVID 
24 months after second 
vaccination 
Blood taken from arterial line at the start 
of dialysis when patient attends for regular 
dialysis session 
Attend UHL blood room for IgG 
antibody testing for COVID