Physiological Versus Right Ventricular Outcome Trial Evaluated for Bradycardia Treatment Upgrades
Phase: NA
Conditions: Pacing-Induced Cardiomyopathy, Heart Failure
Sponsor: Imperial College London

 
 
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Clinical Trial 
Protocol 
 
 
 
 
 
Physiological vs Right ventricular pacing Outcome Trial Evaluated for BradyCardia 
Treatment Upgrades 
 
 
Version 5.0  
 
 
SPONSOR: Imperial College London  
 
FUNDER: Academic grant Heart Research UK  
 
TRIAL COORDINATION CENTRE: Hammersmith Hospital London 
 
NRES reference: NRES Committee Greater Manchester West  
 
Clinicaltrials.gov reference: NCT06052475 
 
 
 
Protocol authorised by: 
 
Name & Role 
Date 
Signature 
Daniel Keene (CI) 
 
 
 
 
Trial Management Group 
 
Chief Investigator 
Dr. Daniel Keene 
Co-investigators: 
Dr Nandita Kaza 
Dr. Matthew Shun-Shin 
Dr. Zachary Whinnett 
Professor Darrel Francis 
Statistician 
Professor Darrel Francis 
Trial Manager 
Miss Aya Khalil 

 
 
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Clinical Queries 
Clinical queries should be directed to Dr Daniel Keene (d.keene@imperial.ac.uk) 
 
Sponsor 
 
Imperial College London is the main research Sponsor for this Trial.  For further information regarding 
the sponsorship conditions, please contact the Head of Regulatory Compliance at: 
 
 
 
Research Governance and Integrity Team 
Imperial College London and Imperial College Healthcare NHS Trust 
Room 215, Level 2, Medical School Building 
Norfolk Place 
London, W2 1PG 
Tel: 0207 594 1862 
Imperial College - Research Governance and Integrity Team (RGIT) Website 
 
 
Funder 
 
This Trial is funded by an academic grant from Heart Research UK.  
 
This protocol describes the Trial (‘Physiological vs Right ventricular pacing Outcome Trial Evaluated for 
bradyCardia Treatment Upgrades IRAS ID 323165) and provides information about procedures for 
entering participants.  Every care was taken in its drafting, but corrections or amendments may be 
necessary. These will be circulated to investigators in the trial.  Problems relating to this trial should be 
referred to the Chief Investigator in the first instance.  
This trial will adhere to the principles outlined in the NHS Research Governance Framework for Health 
and Social Care (2nd edition).  
 
It will be conducted in compliance with the protocol, the Data Protection Act and other regulatory 
requirements as appropriate.  
 
 
 
 
 
 

 
 
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Table of Contents: 
1.1 
BACKGROUND AND RATIONALE FOR CURRENT TRIAL ................................... 6 
2.  TRIAL OBJECTIVES ................................................................................................ 7 
3.  TRIAL DESIGN ......................................................................................................... 8 
4. 
PARTICIPANT ENTRY ...................................................................................... 10 
4.1 
PRE-REGISTRATION EVALUATIONS ................................................................... 10 
4.2 
INCLUSION CRITERIA ............................................................................................ 10 
4.3 
EXCLUSION CRITERIA ........................................................................................... 10 
5. 
ADVERSE EVENTS .......................................................................................... 10 
5.1 
DEFINITIONS ............................................................................................................ 10 
5.2 
REPORTING PROCEDURES .................................................................................. 11 
6. 
ASSESSMENT AND FOLLOW UP .................................................................. 12 
7. 
STATISTICS AND DATA ANALYSIS .............................................................. 13 
8. 
REGULATORY ISSUES .................................................................................... 14 
8.1 
ETHICS APPROVAL ................................................................................................ 14 
8.2 
CONSENT ................................................................................................................. 14 
8.3 
CONFIDENTIALITY .................................................................................................. 15 
8.4 
INDEMNITY ............................................................................................................... 15 
8.5 
SPONSOR................................................................................................................. 15 
8.6 
FUNDING .................................................................................................................. 15 
8.7 
AUDITS ..................................................................................................................... 16 
9. 
TRIAL MANAGEMENT ..................................................................................... 16 
10. 
PUBLICATION POLICY .................................................................................... 16 
 
 
 
 
 
 

 
 
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TRIAL SUMMARY 
 
TITLE 
Physiological vs Right ventricular pacing Outcome Trial Evaluated for bradyCardia 
Treatment Upgrades 
DESIGN 
It is a double-blind, randomized multi-centre trial. A total of 155 participants, considered for 
clinical pacemaker upgrade (placement of an additional pacing lead aiming to deliver more 
physiological ventricular activation; either within the coronary sinus (biventricular pacing) or 
at the Bundle of His or Left Bundle Area (Conduction System Pacing) undergo randomised 
crossover periods of 1 month and 6 months in either RV pacing (continued original pacing 
strategy) or with the more physiological pacing strategy. The crossover periods will enable 
assessment of the utility of clinically performed device upgrades. 
AIMS 
This trial will aim to study the utility of upgrading patients to physiological pacing from right 
ventricular (RV) pacing focusing on patients with mild or moderate impairment of cardiac 
function.  
OUTCOME 
MEASURES 
The primary outcome measure will be SF36 quality of life questionnaire physical 
component summary score   
POPULATION 
The trial will recruit 155 participants scheduled for clinical device upgrade either at the time 
of generator replacement or at any other timepoint.  
ELIGIBILITY 
Adults with an LVEF 35-50% AND >40% RV pacing AND at least one of the following:  
(1) EF reduced by >5% or increase in LVESV by 10ml since implant 
(2) NT-proBNP >250ng/L in sinus rhythm 
(3) NT-proBNP >750ng/L in Atrial Fibrillation 
(4) Left Atrial Volume index >30ml/m2 
(5) Regular loop diuretics prescribed 
(6) Decline in daily patient activity by >1hour per day since implant 
(7) Decrease in device measured thoracic impedance 
(8) Patient reported decline in functional class / exercise tolerance 
DURATION 
o 
18 months for patient recruitment 
o 
15 month follow up period. 
o 
3-month analysis and provisional reporting 
Total duration: 36 months  
 
 

 
 
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GLOSSARY OF ABBREVIATIONS 
AE 
Adverse Event 
AR 
Adverse Reaction 
CA 
Competent Authority 
CCMO 
Central Committee on Research Involving Human Subjects 
DSMB 
Data Safety Monitoring Board 
EU 
European Union 
EudraCT European drug regulatory affairs Clinical Trials  
GCP 
Good Clinical Practice 
GDPR 
HFrEF 
General Data Protection Regulation 
Heart Failure with reduced Ejection Fraction 
IB 
Investigator’s Brochure 
IC 
Informed Consent 
IMP 
Investigational Medicinal Product  
IMPD 
LVEF 
LBB 
LBBB 
LBBP 
Investigational Medicinal Product Dossier  
Left Ventricular Ejection Fraction 
Left Bundle Branch 
Left Bundle Branch Block 
Left Bundle Branch Pacing 
NYHA 
New York Heart Association functional class 
(S)AE 
(Serious) Adverse Event  
Sponsor 
The sponsor is the party that commissions the organisation or performance of 
the research, for example a pharmaceutical 
company, academic hospital, scientific organisation or investigator. A party that 
provides funding for a trial but does not commission it is not regarded as the 
sponsor but referred to as a subsidising party. 
SUSAR  
Suspected Unexpected Serious Adverse Reaction 
 
 
KEYWORDS 
 
Cardiac Resynchronisation  
HIS Bundle Pacing  
Left Bundle Branch Pacing 
Device Upgrade 

 
 
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1. 
INTRODUCTION  
 
1.1 
BACKGROUND AND RATIONALE FOR CURRENT TRIAL 
 
Today, patients who are scheduled to receive a pacemaker for the first time and are expected 
to have high burden of RV pacing (>20/40%), with any (i. e., mild, moderate, or severe) degree 
of LV impairment are guideline recommended to receive a physiological pacing strategy rather 
than RV pacing. RCTs, observational studies and meta-analysis data provide strong evidence 
that this improves patient symptoms, echocardiographic markers, morbidity and even 
mortality. 
 
Patients with existing RV pacemakers, are frequently upgraded clinically using this same 
rationale, existing observational data sets and meta-analysis data that physiological pacing 
strategies are less damaging to cardiac function than ongoing RV pacing. RCTs currently 
though have only evaluated upgrade procedures in patients with severe LV impairment.  
 
The trial aims to provide high-quality RCT evidence for upgrading patients to physiological 
pacing strategies for those patients with mild or moderate LV impairment. This represents a 
large patient cohort susceptible to morbidity and mortality from continued RV pacing. RV 
pacing saves lives in the short-term by preventing bradycardia but can lead to LV impairment 
in the longer term, increasing rates of heart failure and death. Two RCTs have demonstrated 
the harm of RV pacing.  
 
In the DAVID trial, patients with an impaired LV were randomised to back-up pacing 
(minimising RV pacing), or obligatory RV pacing (maximising RV pacing). The group that 
received a high percentage of RV pacing had markedly higher rates of heart failure and death 
from 16.1% to 26.7% (HR 1.61). We have previously a meta-analysis of randomized controlled 
trials (RCTs) and observational studies assessing device upgrades. We analysed studies of 
biventricular (BiV) pacing (6 RCTs of 161 patients, and 46 observational studies of 2,795 
patients) and Conduction system pacing (CSP) upgrades (7 studies of 197 patients) 
separately.11-68 RCTs of BiV pacing upgrade showed LVEF improvement of +8.4% from 
34.4%, and observational studies showed LVEF improvement of +8.5% from 25.7%. 
Observational studies of CSP upgrade showed LVEF improvement of +11.2% from 38.4%. 
LVESV decreased significantly by -25.4mls, -23.7mls, and -19.8mls in BiV RCTs, BiV 
observational studies and CSP observational studies respectively. NYHA class improved by -

 
 
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0.4, -0.8 and -1.0 respectively. RCTs of BiV pacing upgrade found improvements in Minnesota 
Heart Failure Score (-6.9 points) and peak oxygen uptake (+1.1ml/kg/min,). This was also 
seen in observational BiV upgrade studies (-19.7 points and +2.6ml/kg/min respectively). 
 
2.  TRIAL OBJECTIVES 
 
We aim to test whether the positive effects of upgrading to physiological pacing strategies 
translate into benefit for patients with mild, or moderate impairment to their ventricles as a 
result of RV pacing. 
We hypothesise that upgrade to physiological pacing strategies even when the extent of 
cardiac impairment is only mild or moderate will result in significant symptomatic and 
physiological benefit. 
 
Primary Objectives: 
This trial will evaluate, in patients with existing RV pacemakers and only mild or 
moderate LV impairment, whether clinically used modern physiological pacing 
strategies rather than continued RV pacing improve quality-of-life as measured by SF-
36 questionnaire physical component summary score under double-blinded 
conditions? 
Secondary Objectives: 
1. In patients with RV pacemakers and existing mild to moderate LV impairment, what is 
the effect of modern physiological pacing strategies rather than continued RV pacing 
on:  
(a) Left ventricular ejection fraction.  
(b) Left ventricular end systolic index.  
(c) Quality of life questionnaires as measured by the Minnesota Living with Heart 
Failure Questionnaire, EQ5D5L and SF-36 questionnaire overall score. 
(d) Six-minute walk test  
(e) Atrial fibrillation   
(f) Patient preference based on blinded symptomatic preference 
2. Is upgrading to physiological pacing more beneficial at time of generator change or at 
an earlier timepoint? 
3. What are the complications associated with upgrade procedures?  
 
 
 

 
 
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3.  TRIAL DESIGN 
 
 3.1 Trial protocol 
 
Eligible patients will be those considered clinically for a device upgrade by their clinical team. 
Patients will be invited to participate in the trial before their planned clinical procedure. 
 
All participants will undergo an upgrade procedure and receive either Conduction System 
Pacing (His or Left Bundle pacing) as first line approach or Biventricular Pacing if Conduction 
System Pacing cannot be delivered. An experienced operator will carry out the procedures. 
 
Participants will be allocated in blinded random fashion to pacing periods using randomisation 
software (sealed envelope). They will be randomised to either having their ‘physiological 
pacing strategy active OR continued RV pacing. Participants will undergo two one-month 
crossover periods and then two six-month crossover periods. Participants undergo the same 
evaluations at each visit.   
 
At baseline and at the end of each period the participants will have the following assessed: 
- 
Validated Quality-of-Life Questionnaire SF-36 questionnaire 
- 
Minnesota Living with Heart Failure 
- 
EQ5D5L questionnaires.  
- 
6-min walking test 
- 
blood tests including NT-proBNP  
- 
Echocardiography 
- 
data collection regarding any heart failure hospitalisations  
- 
medication list 
- 
Pacing parameters: arrhythmia burden, pacing percentages, daily patient activity. 
 
After the 2x 1-month periods and after the 2x 6-month periods, blinded patient preference will 
be asked on a 7-point preference scale. Again, at the end, they will be asked for their 
symptomatic preference. Participants will be invited to participate in the trial before their 
planned clinical investigation. Each participant will have a run-in period of 1 month, and then 
be followed-up at one-monthly intervals by a central trial hub followed by six-monthly intervals.  
 
3.2 Trial End 
 
The trial ends when the last enrolled trial participant completes their last follow-up at fifteen 
months following their upgrade date. The trial end date is defined as the date the last 

 
 
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participant’s second 6-month period comes to an end and all the research procedures 
occurring at this timepoint are completed.   
 
Any procedures occurring as part of the research study will be reviewed in the Imperial College 
Healthcare NHS Trust weekly multi-disciplinary team meeting, which includes a group of 
consultant cardiologists. Any complications resulting from these research procedures will be 
formally presented, evaluated and discussed within the MDT. If any concerning trends are 
identified as a result of these research procedures, a decision will be made to end the trial 
early.  
 
3.3  Trial outcome measures 
 
Primary outcome measure: 
 
The primary outcome is quality-of-life as measured by SF-36 questionnaire physical 
component summary score under double-blinded conditions. It is mandatory for participants 
to complete the SF-36 questionnaire physical component summary score at baseline, months 
1, 2, 8, and 14 for essential data points. Additional submissions between these periods are 
optional, providing participants flexibility for more frequent updates on their quality of life. 
 
Secondary outcome measure:  
 
1. In patients with RV pacemakers and existing mild to moderate LV impairment, what is 
the effect of modern physiological pacing strategies rather than continued RV pacing 
on:  
(a) Left ventricular ejection fraction.  
(b) Left ventricular end systolic index.  
(c) Quality of life questionnaires as measured by the Minnesota Living with Heart 
Failure Questionnaire, EQ5D5L and SF-36 questionnaire overall score. 
(d) Six-minute walk test  
(e) Atrial fibrillation   
(f) Patient preference based on blinded symptomatic preference. 
2. Is upgrading to physiological pacing more beneficial at time of generator change or at 
an earlier timepoint? 
3. What are the complications associated with upgrade procedures? 
 

 
 
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4. 
PARTICIPANT ENTRY  
 
4.1 
PRE-REGISTRATION EVALUATIONS 
 
We will recruit patients who are referred for clinically indicated cardiac resynchronisation 
therapy upgrade.  
 
PIC sites will identify patients meeting eligibility criteria with high burden RV pacing who are 
clinically indicated for an upgrade procedure. These patients will then undergo their upgrade 
procedure at ICHT - Hammersmith Hospital (as these PIC sites do not offer the conduction 
system pacing upgrade procedure). 
 
 4.2 
INCLUSION CRITERIA 
 
Adults with an RV pacemaker and LVEF 35-50% who are clinically indicated for an upgrade 
procedure plus any of the following:  
o EF reduced by >5% or increase in LVESV by 10ml since implant.  
o NT-proBNP >250ng/L in sinus rhythm 
o NT-pro BNP>750ng/L if AF 
o Left atrial volume index >30 mL/m2 
o Regular loop diuretics prescribed. 
o Decline in daily patient activity by >1 hour per day since implant. 
o Decrease in device measured thoracic impedance. 
o Patient reported decline in functional class / exercise tolerance. 
 
4.3 
EXCLUSION CRITERIA 
 
o Inability to provide informed consent.  
o Aged under 18  
o Pregnant women.  
 
5. 
ADVERSE EVENTS 
 
Any complications resulting from these research procedures will be formally presented, 
evaluated and discussed within the Imperial College Healthcare NHS Cardiology MDT. If any 
concerning trends are identified as a result of these research, a decision will be made to end 
the trial early.  
 
5.1 
DEFINITIONS   
 

 
 
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Adverse Event (AE): any untoward medical occurrence in a patient or clinical trial subject.   
Serious Adverse Event (SAE): any untoward and unexpected medical occurrence or effect 
that: 
o Results in death 
o Is life-threatening – refers to an event in which the subject 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. 
o Requires hospitalisation, or prolongation of existing inpatients’ hospitalisation. 
o Results in persistent or significant disability or incapacity 
o Is a congenital anomaly or birth defect. 
 
 
Medical judgement should be exercised in deciding whether an AE is serious in other 
situations.  Important AEs that are not immediately life-threatening or do not result in death or 
hospitalisation but may jeopardise the subject or require intervention to prevent one of the 
other outcomes listed in the definition above should also be considered serious. 
 
5.2 
REPORTING PROCEDURES 
 
All adverse events should be reported. Depending on the nature of the event, the reporting 
procedures below should be followed. Any questions concerning adverse event reporting 
should be directed to the Chief Investigator in the first instance.   
 
5.2.1 Non-serious AEs 
 
All such events, whether expected or not, should be recorded.   
 
5.2.2 Serious AEs 
 
An SAE form should be completed and emailed to the Chief Investigator within 24 
hours.  However, relapse and death due to pre-existing medical problems and 
hospitalisations for elective treatment of a pre-existing condition do not need reporting 
as SAEs. 
 
All SAEs should be reported to the REC (NRES Committee Greater Manchester West) 
where in the opinion of the Chief Investigator, the event was: 
o ‘related’, i.e., resulted from the administration of any of the research 
procedures; and 

 
 
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o ‘unexpected’, i.e., an event that is not listed in the protocol as an expected 
occurrence. 
Reports of related and unexpected SAEs should be submitted within 15 days of the 
Chief Investigator becoming aware of the event, using the NRES SAE form for non-
IMP studies.  The Chief Investigator must notify the Sponsor of all related and 
unexpected SAEs.  
 
Local investigators should report any SAEs as required by their Local Research Ethics 
Committee, Sponsor and/or Research & Development Office. 
Contact details for reporting SAEs: 
RGIT@imperial.ac.uk 
Please send SAE forms to: d.keene@imperial.ac.uk  
Tel: 020 7594 1093 (Mon to Fri 09.00 – 17.00) 
 
6. 
ASSESSMENT AND FOLLOW UP 
  
 
Post-procedure, the participant will be followed up by their clinical team. Pacing checks will be 
undertaken as per clinical protocol and standard of care. All patients pacing notes will be 
marked as indicating the patient is involved in a clinical trial and clinical team should not 
disclose to the patient the pacing period allocation. 
 
At every timepoint for research follow-ups following the participant’s pacemaker upgrade i.e. 
at the 1-month, 2-months, 8-months and 14-month timepoint – we will collect:  
 
o Validated Quality-of-Life Questionnaire SF-36, Minnesota Living with Heart Failure, 
and EQ5D5L questionnaires.  
o 6-min walking test 
o blood tests incl. NT-proBNP 
o Echocardiography 
o data collection regarding any heart failure hospitalisations  
o medication list 
o Pacing parameters: arrhythmia burden, pacing percentages, daily patient activity. 
 
Patient’s Quality of life will be assessed monthly via the SF36 validated quality of life 
questionnaire and this will be done either electronically or via telephone, according to patient’s 
preference. Patient symptoms will also be assessed monthly via custom symptom 

 
 
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questionnaires (non-validated) in the one-month crossover periods and then monthly in the 
six-month crossover periods. Participants can choose whether to participate in monthly 
questionnaires, and it's entirely optional for those who are willing to take part in the monthly 
assessment.  
 
Incidental findings identified as part of the research protocol will be reviewed and reported by 
trained clinical members of the research team.  Any incidental findings identified will be 
communicated to the participant’s clinical team as well as their GP as per standard protocol. 
 
7. 
STATISTICS AND DATA ANALYSIS 
 
7.1 Sample size calculations:  
The sample size calculation for the PROTECT UP cross over RCT is as follows: 
Assuming standard deviation of difference of sequential measurements of SF35 of 10 units, 
136 patients (68 in each arm – on/off or off/on) would provide 80% power at the 5% 
significance threshold to detect a 3.5-unit difference in SF36 Physical Component Score 
between the upgraded physiological pacing strategy and standard of care RV pacing. To 
account to loss to follow-up of 12% we will recruit and randomise 155 patients. Patients will 
only be randomised after successful upgrade. 
 
Our primary outcome will use the longest available comparable period, ideally the 6-month 
duration periods, but if participants have elected to withdraw because of overwhelming patient 
perceived blinded benefit/harm we will use their blinded QOL assessment from the longest 
available period. If participants wish to withdraw during a pacing period because of poor 
symptoms we will aim to perform endpoint assessment at that point in a blinded fashion and 
use that data. 
 
7.2 Statistical Analysis:  
Analysis will be performed according to the ITT principle and all statistical tests will be two-
tailed with a 5% significance level.  
 
The primary and secondary continuous secondary endpoints (SF-36 individual and global 
components, MLWHF, daily patient activity, LVEF, LVESI, 6-minute walk test and patient 
preference, BNP) will be analysed using a mixed-effect modelling approach, including the 
treatment and randomisation order as independent variables. 
 

 
 
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For time-to-event endpoints (death and hospitalisation for heart failure), the hazard ratio and 
respective 95% confidence interval will be computed using the Cox proportional hazards 
regression model, or appropriate alternative. 
 
In secondary analysis the model will be adjusted for clinical important confounders that will be 
pre-specified in the statistical analysis plan. The underlying assumptions of any fitted model 
will be assessed as appropriate. 
 
We will test the impact of relevant subgroups (time of upgrade (ERI vs Early upgrade), timing 
of improvement (one month vs 6 month) presence of AF, percentage pacing, BIV vs CSP 
pacing approach) by testing the interaction of these variables on the treatment. 
 
Data and all appropriate documentation will be stored for a minimum of 10 years after the 
completion of the trial, including the follow-up period.   
 
8. 
REGULATORY ISSUES 
 
8.1 
ETHICS APPROVAL 
 
The Trial Coordination Centre has obtained approval from the Greater Manchester 
West Research Ethics Committee (REC) and Health Research Authority (HRA). The 
trial must also receive confirmation of capacity and capability from each participating 
NHS Trust before accepting participants into the trial, or any research activity is carried 
out. The trial will be conducted per the recommendations for physicians involved in 
research on human subjects adopted by the 18th World Medical Assembly, Helsinki 
1964 and later revisions. 
 
8.2 
CONSENT  
 
Consent to enter the trial must be sought from each participant only after a complete 
explanation, an information leaflet offered, and time allowed for consideration.  Signed 
participant consent should be obtained. There will be no pre-specified window for 
consenting patients; patients can consent to take part in the trial up until the day of 
their procedure. The right of the participant to refuse to participate without giving 
reasons must be respected.   
 
Patient consent for a referral to the research team and transfer of their data will be 
documented in patient notes. 

 
 
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After the participant has entered the trial, the clinician remains free to give alternative 
treatment to that specified in the protocol at any stage if they feel it is in the participant’s 
best interest. Still, the reasons for doing so should be recorded.  In these cases, the 
participants remain within the trial for follow-up and data analysis.  All participants are 
free to withdraw from the protocol treatment at any time without giving reasons or 
prejudicing further treatment 
 
8.3 
CONFIDENTIALITY 
 
The Chief Investigator will preserve the confidentiality of participants participating in 
the trial and is registered under the Data Protection Act. 
 
Data will be pseudonymised using a number code which can only be linked to 
personally identifiable information kept in a separate record. The code will replace all 
personally identifiable information in the primary records used for the trial.  
 
8.4 
INDEMNITY 
 
Imperial College London holds negligent harm and non-negligent harm insurance 
policies, which apply to this trial. 
 
8.5 
SPONSOR 
 
Imperial College London will act as the main Sponsor for this trial. Delegated 
responsibilities will be assigned to the NHS trusts taking part in this trial. 
 
8.6 
FUNDING 
 
The Trial is funded by an academic grant from the Heart Research UK Charity.  
 
As we are requiring participants to attend hospital for reasons aside from their usual 
clinical care, we will be able to offer expenses for participant’s travel and refreshments. 
All the trial visits will be undertaken at Imperial College London, Hammersmith 
Hospital. Neither the clinical team nor members of the research team will receive any 
financial incentives as a result of inviting participants to take part in this research.   
 

 
 
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8.7 
AUDITS  
 
The trial may be subject to inspection and audit by Imperial College London under their 
remit as the sponsor and other regulatory bodies to ensure adherence to GCP and the 
NHS Research Governance Framework for Health and Social Care (2nd edition).  
 
An independent Data Monitoring Committee (DMC) will be set up to review data for 
safety and efficacy at regular intervals. The DMC will prepare a charter (in line with the 
DAMOCLES recommendations) outlining their responsibilities and reporting 
requirements. 
 
An independent Data Monitoring Committee (DMC) will be set up to review data for 
safety and efficacy at regular intervals. The DMC will prepare a charter (in line with the 
DAMOCLES recommendations) outlining their responsibilities and reporting 
requirements. 
 
9. 
TRIAL MANAGEMENT 
 
The day-to-day management of the trial will be coordinated through Dr Daniel Keene 
(d.keene@imperial.ac.uk), Dr Nandita Kaza (n.kaza@imperial.ac.uk) and Aya Khalil 
(akhalil@ic.ac.uk).    
 
10. 
PUBLICATION POLICY 
 
We will seek to publish the trial’s results in internal reports, scientific presentations and peer-
reviewed scientific journals. The scientific team will make all analyses and decisions to publish 
and will not be influenced by the funder.