Supported Rescue Packs Post-discharge in Chronic Obstructive Pulmonary Disease: An Open-label Multicenter Randomised Controlled Trial
Phase: PHASE3
Conditions: COPD, COPD Exacerbation
Sponsor: Guy's and St Thomas' NHS Foundation Trust

Confidential    
Confidentiality and Copyright: This document is confidential and property of King’s Clinical Trials Unit. This document may not be copied, 
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RAPID_Trial_Protocol_v4.0_05112024_.docx 
      Page 1 of 34 
 
                  IRAS 331831 
 
 
PROTOCOL FULL TITLE: 
Supported Rescue packs post-discharge in chronic obstructive 
pulmonary disease: An open-label multicentre randomised controlled 
trial  
 
Protocol Short Title/ Acronym: 
RAPID 
Trial Identifiers  
IRAS Number: 
331831 
ISRCTN 
Number/ 
Clinical 
trials.gov 
Number: 
ISRCTN44283921 
 
NCT06347536 
Funders Number: 
NIHR156698 
Protocol 
Version 
Number: 
4.0 
Date: 
05/11/2024 
 
Co-Sponsors 
Name: 
King’s College London  
Professor Bashir Al-Hashimi 
Vice President (Research and Innovation) 
Address: 
Strand Building 
Strand Campus, Strand, London, WC2R 2LS 
Telephone: 
 
Email: 
bashir.al-hashimi@kcl.ac.uk  
 
Name: 
Guy’s and St Thomas’ NHS Foundation Trust  
Rachel Fay 
Address: 
16th Floor. Tower Wing 
Guy’s & St Thomas’ Foundation NHS Trust 
Great Maze Pond 
London 
SE1 9RT 
Telephone: 
020 7188 7188 

Acronym: RAPID                                                                                                                           Version 4.0  Date 05/11/2024 
  
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IRAS 331831 
Email: 
R&D@gstt.nhs.uk  
 
Chief Investigator 
Name: 
Professor Mona Bafadhel 
 
Address: 
King’s Centre for Lung Health, King’s College London, London, UK 
School of Immunology and Microbial Sciences 
5th Floor Tower 
Guys Campus 
SE1 9RT 
 
Telephone: 
0207 848 0606 
 
Email: 
mona.bafadhel@kcl.ac.uk  
 
Signature 
 
Date: 31/01/2025 
 
Academic co-lead 
Name: 
 Professor John Hurst 
Address: 
UCL Respiratory, University College London, 114 Rayne Building, London, 
WC1E 6JF, United Kingdom 
Telephone: 
0208 016 8364 
Email: 
j.hurst@ucl.ac.uk  
Signature 
 
Date: 31/01/2025 
 
 
Statisticians 
Name: 
1. Professor Toby Prevost 
2. Joana Vasconcelos  
Address: 
Nightingale-Saunders Clinical Trials & Epidemiology Unit @ King's CTU 
Florence Nightingale Faculty of Nursing, Midwifery & Palliative Care King's 
College London 
Telephone: 
N/A 

Acronym: RAPID                                                                                                                           Version 4.0  Date 05/11/2024 
  
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IRAS 331831 
 
Email: 
1. toby.prevost@kcl.ac.uk   
2. joana.vasconcelos@kcl.ac.uk   
Signature 
 
Date: 31/01/2025 
 
Health Economist 
Name: 
Dr Huajie Jin 
Address: 
David Goldberg Centre 
18 De Crespigny Park, London, SE5 8AF 
Telephone: 
+44 (0) 20 7848 0878 
Email: 
huajie.jin@kcl.ac.uk 
 
Methodologist 
Name: 
1. Professor Graham Martin  
2. Dr Karolina Kuberska 
Address: 
1. The Healthcare Improvement Studies Institute (THIS Institute), University of 
Cambridge, Strangeways Research Laboratory, 2 Worts' Causeway, Cambridge 
CB1 8RN  
2. The Healthcare Improvement Studies Institute (THIS Institute), University of 
Cambridge, Strangeways Research Laboratory, 2 Worts' Causeway, Cambridge 
CB1 8RN 
Telephone: 
1. +4401223760058 
2. +4401223761881 
Email: 
1. graham.martin@thisinstitute.cam.ac.uk 
2. karolina.kuberska@thisinstitute.cam.ac.uk  
 
Clinical Trials Unit 
Name: 
Caroline Murphy 
Address: 
King’s Clinical Trials Unit  
IoPPN, King’s College London, London SE5 8AF, UK 
Telephone: 
+44 20 7848 0532 
Email: 
ctu@kcl.ac.uk  
 
 Trial Manager 

Acronym: RAPID                                                                                                                           Version 4.0  Date 05/11/2024 
  
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IRAS 331831 
Name: 
Olena Said 
Address: 
King’s Clinical Trials Unit  
IoPPN, King’s College London, London SE5 8AF, UK 
Telephone: 
+44 20 7848 0532 
Email: 
rapid-rescue@kcl.ac.uk  
 
 
 

Acronym: RAPID                                                                                                                           Version 4.0  Date 05/11/2024 
  
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IRAS 331831 
Study Synopsis 
TITLE OF CLINICAL TRIAL: 
SUPPORTED RESCUE PACKS POST-DISCHARGE IN 
CHRONIC OBSTRUCTIVE PULMONARY DISEASE: AN 
OPEN-LABEL 
MULTICENTER 
RANDOMISED 
CONTROLLED TRIAL 
Protocol Short Title/ Acronym: 
RAPID 
Study Phase: 
Phase 3  
Sponsor Name(s): 
King’s College London and Guy’s and St Thomas Hospital NHS 
Foundation Trust 
Chief Investigator(s): 
Professor Mona Bafadhel 
 
Academic co-lead: 
Professor John Hurst 
Medical Condition or Disease Under 
Investigation: 
Chronic Obstructive Pulmonary Disease (COPD) 
Purpose of Clinical Trial: 
To test the hypothesis that provision of a rescue pack of antibiotics 
and corticosteroids, together with written (and translated) 
education on their use and twice-weekly telephone (or text) based 
support for when to use rescue packs, can reduce all-cause 
hospital re-admission in the 90-day high-risk period following 
discharge from hospital after an exacerbation of COPD. 
Primary Outcome: 
Time to first all-cause readmission within 90 days of discharge 
from hospital 
• 
Secondary Outcome(s): 
• 
Time to and frequency of COPD-related readmissions at 30 
and 90 days 
• 
Days alive and out of hospital at day 90 
• 
Time to and frequency of all COPD exacerbations at days 30 
and 90 
• 
Cumulative systemic oral corticosteroids use over 90 days 
• 
Cumulative systemic antibiotic use over 90 days 
• 
Health care contacts at baseline, days 90 and 180, and 1 year 
• 
All cause readmission at 30 days 
• 
All cause-, cardiovascular- and COPD- related mortality at 
day 90 and over 12 months 
• 
Quality of life (COPD assessment Test (CAT) score and EQ-
5D-5L) at days 90 and 180, and 1 year 
• 
Incremental cost-effectiveness ratio (ICER, a ratio of the 
additional cost divided by the additional effectiveness of SRP 
compared to UC) at days 90 and 180 and 1 year 

Acronym: RAPID                                                                                                                           Version 4.0  Date 05/11/2024 
  
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IRAS 331831 
• 
Qualitative description of usual care 
• 
Qualitative examination of fidelity to and adaptation of the 
plan in the intervention arm 
• 
Serious adverse events  
• 
Antimicrobial resistance 
 
Trial Design: 
Open label randomised controlled trial, with internal pilot 
Sample Size: 
1400 patients recruited for 1331 analysed to ensure 515 primary 
outcome events needed for 90% power 
Summary of Eligibility Criteria: 
INCLUSION: 
 
• 
Adults aged 40 and over 
• 
Patient to be discharged from hospital with exacerbation of 
COPD 
• 
Able to provide informed consent 
 
EXCLUSION: 
• 
Requirement for invasive ventilation during the hospital 
admission 
• 
Patients who have an expected survival of less than 90 days 
• 
Patients with signs of new consolidation on chest X-ray (if 
available) 
• 
Discharge to residential or nursing home 
• 
Inability to engage with supported self-management 
• 
No access to telephone. 
• 
Existing participation in an interventional trial. 
• 
Previous participation in the RAPID trial. 
 
Intervention (Description, frequency, 
details of delivery) 
Patients allocated to the intervention arm will receive: 
1. a rescue pack (prednisolone and antibiotics for 5-7 days). The 
prescription will conform to local prescribing guidelines for 
antibiotic and systemic corticosteroids for exacerbations of 
COPD. 
2. a written rescue pack management plan. 
3. twice-weekly automated telephone symptom reminder calls 
and/or text messages for 90 days. 
Comparator Intervention: 
Usual care (to be studied and described) – but no provision of a 
rescue pack at discharge. 
Maximum Duration of Treatment of a 
Participant: 
One year from the point of discharge from hospital. 
Version and Date of Final Protocol: 
V2.0 20/06/2024 
 
 
 

Acronym: RAPID                                                                                                                           Version 4.0  Date 05/11/2024 
  
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IRAS 331831 
Revision History 
Protocol version 
Description of changes from previous revision 
Effective 
Date 
Protocol Version 4.0 
- 
Addition of further exclusion criteria: 
- 
Patients with signs of new consolidation on 
chest X-ray (if available) 
- 
Previous participation in the RAPID trial. 
 
Protocol Version 3.1 
- 
Clarification around pneumonic exacerbations 
of COPD and pneumonia on X-ray 
24/09/2024 
Protocol Version 3.0 
- 
Removal from exclusion criterion: Individuals 
discharged from hospital to a non-physical 
virtual ward. 
- 
Addition of Dyspnea VAS as part of standard 
practice 
- 
Clarification on the definition of discharge from 
hospital 
- 
Addition of definition of moderate and severe 
exacerbations of COPD 
- 
Addition 
of 
clarifications 
regarding 
randomisation strata 
- 
Clarifications around SAEs added as additional 
source data for primary outcome alongside HES 
data 
20/09/2024 
Protocol Version 2.0 
- 
Additon of exclusion criterion: Individuals 
discharged from hospital to a non-physical 
virtual ward. 
- 
Addition of modified MRC measure. 
- 
Clarification of safety reporting procedures. 
 
03/07/2024 
Protocol Version 1.0  
First approved version of Protocol 
 
 
 
 

Acronym: RAPID                                                                                                                           Version 4.0  Date 05/11/2024 
  
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IRAS 331831 
Glossary of terms  
 
 
 
 
 
 
AE/AR 
Adverse Event/Adverse Reaction 
 
ITT 
Intention to Treat 
AMR 
Anti-mircrobial Resistance 
 
KCL 
King’s College London 
ARG 
Andibiotic Resistance Gene 
 
KCTU  
King’s Clinical Trials Unit  
 
 
 
KHP-CTO 
King’s Health Partners Clinical Trials Office 
BNF 
British National Formulary 
 
 
 
 
 
 
 
 
CA 
Competent Authority 
 
MAR  
Missing at Random 
CAT 
COPD Assessment Test 
 
MTA 
Material Transfer Agreement 
 
 
 
NHS 
National Health Service 
 
 
 
NIHR 
National Institute for Health and Care Research 
CI 
Chief Investigator 
 
NACAP 
The National Asthma and COPD Audit Programme 
CONSORT 
Consolidated Standards of Reporting Trials 
 
ONS 
Office of National Statistics 
COPD 
Chronic Obstructive Pulmonary Disease 
 
PI 
Principal Investigator (at site) 
CRF 
Case Report Form 
 
PIN 
Participant Identification Number 
CRT 
Community Respiratory Team 
 
PIS 
Participant Information Sheet  
CSV 
Comma-Separated Values 
 
PP 
Per Protocol 
CTU 
Clinical Trials Unit 
 
QALY 
Quality-Adjusted Life-Years 
DCR 
Data Clarification Request 
 
R&D 
Research and Development 
DMC 
Data Monitoring Committee 
 
RA 
Regulatory Agency 
DOB 
Date of Birth 
 
 
 
DSUR 
Development Safety Update Report 
 
REC 
Research Ethics Committee 
 
 
 
 
 
eCRF 
Electronic Case Report Form 
 
RN 
Research Nurse 
 
 
 
 
 
EDC 
Electronic Data Capture 
 
SAE 
Serious Adverse Event 
 
 
 
SAP 
Statistical Analysis Plan 
eSMS 
Emergency Scientific and Medical Services 
 
SDV 
Source Data Verification 
EU 
European Union 
 
 
 
 
 
 
SS 
Senior Statistician 
GDPR 
General Data Protection Regulation 
 
SDW 
Source Data Worksheets 
GP 
General Practitioner 
 
 
 
GCP 
Good Clinical Practice 
 
 
 
HES 
Hospital Episode Statistics 
 
 
 
HRA 
Health Research Authority 
 
TM 
Trial Manager 
 
 
 
TMG 
Trial Management Group 
 
 
 
 
 
 
 
 
TS 
Trial Statistician 
 
 
 
TSC 
Trial Steering Committee 
 
 
 
UCL 
University College London 
ICER 
Incremental Cost-effectiveness Ratio 
 
UK 
United Kingdom 
ICF 
Informed Consent Form 
 
VAS 
Visual Analogue Scale 
ID 
Identifier 
 
VDI 
Virtual Desktop Infrastructure 
IME 
Important Medical Event 
 
 
 
IP 
Intellectual Property 
 
 
 
 
 
 
 
 
 
 
 
 
 

Acronym: RAPID                                                                                                                           Version 4.0  Date 05/11/2024 
  
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IRAS 331831 
PROTOCOL CONTENT 
STUDY SYNOPSIS............................................................................................................................ 5 
GLOSSARY OF TERMS .................................................................................................................. 8 
PROTOCOL CONTENT .................................................................................................................. 9 
1. 
INTRODUCTION .................................................................................................................. 11 
1.1 
BACKGROUND AND RATIONALE ............................................................................................. 11 
2. 
TRIAL DESIGN ..................................................................................................................... 12 
2.1 
OBJECTIVES ........................................................................................................................... 12 
3. 
PARTICIPANTS .................................................................................................................... 13 
3.1 
STUDY SETTING & RECRUITMENT .......................................................................................... 13 
3.2 
ELIGIBILITY CRITERIA ............................................................................................................ 13 
3.3 
IDENTIFICATION OF ELIGIBLE PARTICIPANTS  ......................................................................... 13 
3.4 
INFORMED CONSENT .............................................................................................................. 13 
4. 
DATA COLLECTION & DATA ENTRY........................................................................... 15 
4.1 
PARTICIPANT TIMELINE.......................................................................................................... 15 
4.2 
DATA ENTRY .......................................................................................................................... 17 
4.3 
BASELINE DATA COLLECTION ................................................................................................ 17 
4.4 
EFFICACY DATA ..................................................................................................................... 17 
4.5 
SAFETY DATA ........................................................................................................................ 18 
4.6 
LABORATORY DATA ............................................................................................................... 18 
4.7 
MEASURES TO PROMOTE PARTICIPANT RETENTION ................................................................ 18 
4.8 
QUALITATIVE SERVICE EVALUATION TO CHARACTERISE STANDARD-OF-CARE................... 18 
5. 
QUALITATIVE SUB-STUDY TO UNDERSTAND INTERVENTION DELIVERY ... 19 
6. 
INTERVENTIONS ................................................................................................................ 20 
6.1 
EXPLANATION FOR THE CHOICE OF COMPARATORS ................................................................ 20 
6.2 
INTERVENTION AND COMPARATOR DESCRIPTION, DOSING AND LABELLING ........................... 20 
7. 
ASSIGNMENT OF INTERVENTIONS .............................................................................. 20 
7.1 
RANDOMISATION METHOD ..................................................................................................... 20 
7.2 
RANDOMISATION IMPLEMENTATION ...................................................................................... 20 
8. 
LABORATORIES ................................................................................................................. 20 
8.1 
SAMPLE COLLECTION/LABELLING/LOGGING ......................................................................... 20 
8.2 
SAMPLE ANALYSIS PROCEDURES .......................................................................................... 20 
8.3 
SAMPLE DATA RECORDING/REPORTING ................................................................................ 20 
8.4 
SAMPLE INCIDENTS ................................................................................................................ 21 
9. 
DATA MANAGEMENT ....................................................................................................... 21 
9.1 
DATA MANAGEMENT ............................................................................................................. 21 
9.2 
DATA SECURITY ..................................................................................................................... 21 
9.3 
DATA QUALITY PROCESSES .................................................................................................... 23 
9.4 
DATABASE LOCK ................................................................................................................... 22 
10. 
SUMMARY OF KNOWN AND POTENTIAL RISK OF RESCUE PACKS ................. 23 
11. 
ADVERSE EVENT MANAGEMENT AND REPORTING .............................................. 24 

Acronym: RAPID                                                                                                                           Version 4.0  Date 05/11/2024 
  
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IRAS 331831 
11.1 
EVALUATING AES AND SAES ............................................................................................... 24 
11.2 
ADVERSE EVENT PROCESSING RESPONSIBILITIES ................................................................ 26 
12. 
ETHICS APPROVAL ........................................................................................................... 26 
12.1 
PROTOCOL AMENDMENTS AND VERSION CONTROL OF STUDY DOCUMENTS......................... 26 
13. 
STATISTICAL METHODS ................................................................................................. 26 
13.1 
PRIMARY OUTCOME ............................................................................................................ 26 
13.2 
SECONDARY OUTCOMES ..................................................................................................... 26 
13.3 
SAMPLE SIZE JUSTIFICATION ............................................................................................... 27 
13.4 
STATISTICAL METHODS FOR PRIMARY AND SECONDARY OUTCOMES .................................. 27 
13.5 
INTERIM ANALYSES (STATISTICAL) ..................................................................................... 25 
13.6 
METHODS FOR PRE-SPECIFIED SUBGROUP ANALYSES ......................................................... 28 
13.7 
METHODS TO HANDLE MISSING DATA ................................................................................. 28 
13.8 
PLANS TO GIVE ACCESS TO THE FULL PROTOCOL AND PARTICIPANT LEVEL-DATA .............. 28 
13.9 
HEALTH ECONOMIC ANALYSIS .......................................................................................... 28 
14. 
OVERSIGHT AND MONITORING  .................................................................................. 30 
14.1 
TRIAL MANAGEMENT GROUP (TMG) ................................................................................... 30 
14.2 
TRIAL STEERING COMMITTEE (TSC) ................................................................................... 30 
14.3 
DATA MONITORING COMMITTEE (DMC) ............................................................................... 30 
14.4 
MONITORING ...................................................................................................................... 31 
15. 
MISCELLANEOUS............................................................................................................... 31 
15.1 
PLANS FOR INDEPENDENT AUDIT ........................................................................................ 31 
15.2 
DISSEMINATION PLANS ....................................................................................................... 30 
15.3 
END OF TRIAL ..................................................................................................................... 30 
15.4 
CONFIDENTIALITY .............................................................................................................. 30 
15.5 
FUNDING ............................................................................................................................ 31 
15.6 
INSURANCE AND INDEMNITY .............................................................................................. 31 
15.7 
ARCHIVING ......................................................................................................................... 31 
15.8        DATA CONTROLLER ........................................................................................................... 31 
15.9 
INTELLECTUAL PROPERTY .................................................................................................. 31 
16. 
REFERENCES ....................................................................................................................... 32 
 
 
 

Acronym: RAPID                                                                                                                           Version 4.0  Date 05/11/2024 
  
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IRAS 331831 
1. INTRODUCTION  
1.1 BACKGROUND AND RATIONALE  
 
What is the problem being addressed?  
Chronic obstructive pulmonary disease (COPD) is a common lung condition in the United Kingdom, with a 
prevalence of 4.5% in population ≥40 years and rising4. In addition to daily symptoms such as cough and 
breathlessness that limit physical activity, people living with COPD are prone to unpredictable deteriorations 
in their health called ‘exacerbations’. Exacerbations are sometimes severe enough to lead to hospital admission 
and are often driven by infections. A systematic review of patient outcomes in COPD identified exacerbations, 
especially severe hospitalised exacerbations, as the aspect of COPD that patients found most difficult to live 
with5. Prior to the pandemic there were around 115,000 admissions to hospital with COPD exacerbations per 
annum6 and admissions are now returning to that level. Exacerbations are more common in the winter with 
greater circulation of respiratory viruses, and thus the burden of hospitalised exacerbations contributes to 
winter National Health Service (NHS) bed pressures and cost to the NHS. The annual healthcare cost for people 
with moderate and severe exacerbation of COPD in England was estimated to be nearly £1 billion in 20227. A 
particular problem after a hospitalised COPD exacerbation is re-admission to hospital. The National Asthma 
and COPD Audit Programme (NACAP) has shown that the re-admission rate is 23% at 30 days and 43% at 90 
days2. Our systematic review identified comorbidities, previous exacerbations and increased length of stay as 
risk factors for 30- and 90-day all-cause readmission5. 
 
There are many interventions that can reduce the risk of COPD exacerbations but these are incompletely 
effective8. There is also evidence to suggest that earlier intervention with standard exacerbation treatment of 
antibiotics and/or corticosteroids (called a ‘rescue pack’) can hasten recovery, with a lessened chance of 
hospital admission9. As part of standard NHS care2, patients with COPD should have a ‘discharge bundle’ 
implemented, although this is often poorly delivered and has not been definitively shown to impact outcomes 
(likely because the wrong outcomes were chosen, and the bundle was poorly implemented)10. The provision 
of rescue packs is not a standard component of discharge bundles but these are sometimes provided according 
to local service preference3. Additionally, in usual clinical practice, some patients will have been prescribed 
rescue packs from primary care (GP) or a community respiratory team (CRT) prior to being hospitalised with 
COPD. Furthermore, patients may or may not have access to rescue packs from the GP or the CRT after 
hospital discharge. 
 
Although rescue packs are part of NICE guidance2, the available evidence suggests they are not effective unless 
provided in the context of a more comprehensive management/education plan that supports patients in their 
appropriate use11. In practice this usually does not happen3, with evidence that a patient with COPD will receive 
variable or often no support; with some patients receiving rescue packs on demand without considering 
antimicrobial resistance, predictable side-effects from steroid overuse, or reviewing appropriateness. The 
investigators have pilot data that show receiving a rescue pack on hospital discharge is controversial as the 
hospital team is not, in general, the team that provides ongoing support to use these. There is thus recognised 
over- and under-use of rescue packs, associated harm from these medicines and variable provision. Providing 
a rescue pack, with education on how to use and support for when to use, has not been specifically tested in 
the high-risk 90-day period for readmission following a hospitalised exacerbation. We hypothesise that rescue 
packs on discharge from hospital in addition to a comprehensive self-supported management plan, consisting 
of the Asthma+Lung UK written management plan and twice weekly automated phone and or text messaging 
during this 90 day high risk period, will reduce readmissions by 20% compared to standard care.  
 
Why is this research important in terms of improving the health of patients and health and care services?  

Acronym: RAPID                                                                                                                           Version 4.0  Date 05/11/2024 
  
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IRAS 331831 
 
Reducing re-admission through provision of supported rescue pack use would benefit people living with COPD 
and the NHS. A reduction in readmissions of 20% could save the NHS £86 million per quarter (£344 million 
per annum). Conversely, demonstrating that rescue packs are not effective when used in this way will address 
controversy about use, and reduce pressure on antimicrobial resistance and harm from over-use of oral 
corticosteroids. Integrated care systems are rapidly developing out-of-hospital support for people with 
exacerbations of COPD including digitally supported virtual wards. The proposed trial will define the role of 
supported rescue pack provision in the design and implementation of these programmes, enhancing their ability 
to reduce demands on urgent and acute care. Whether positive or negative, this trial will help to reduce the 
current variation in service provision by providing a definitive answer to the study question. Furthermore, 
preventing exacerbations of COPD have been identified as a priority by the James Lind Alliance (JLA) Priority 
Setting Partnership (PSP)12. 
 
 
2. TRIAL DESIGN 
Open label randomised controlled trial, with internal pilot. 
2.1 OBJECTIVES 
2.1.1 PRIMARY OBJECTIVE 
To assess whether rescue packs and a comprehensive supported self-management plan reduce readmissions 
following exacerbation of COPD.  
This study objective is not to test safety or efficacy of rescue packs. The focus is rather on the treatment support 
strategies therefore constituting a non-CTIMP study as per current regulatory requirements. 
2.1.2 SECONDARY OBJECTIVES 
 
• 
Time to and frequency of COPD-related readmissions at 30 and 90 days 
• 
Days alive and out of hospital at day 90 
• 
Time to and frequency of all COPD exacerbations at days 30 and 90 
• 
Cumulative systemic oral corticosteroids use over 90 days 
• 
Cumulative systemic antibiotic use over 90 days 
• 
Health care contacts at baseline, days 90 and 180, and 1 year 
• 
All cause-, cardiovascular- and COPD- related mortality at day 90 and over 12 months 
• 
Quality of life (COPD assessment Test (CAT) score and EQ-5D-5L) at days 90 and 180, and 1 year 
• 
Incremental cost-effectiveness ratio (ICER, a ratio of the additional cost divided by the additional 
effectiveness of SRP compared to UC) at days 90 and 180 and 1 year 
• 
Qualitative description of usual care 
• 
Qualitative examination of fidelity to and adaptation of the plan in the intervention arm 
• 
Serious adverse events 
• 
Antimicrobial resistance 
 

Acronym: RAPID                                                                                                                           Version 4.0  Date 05/11/2024 
  
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IRAS 331831 
3. PARTICIPANTS 
3.1 STUDY SETTING & RECRUITMENT  
The study will be open across NHS-based sites in the United Kingdom. Participants in the trial will be recruited 
during the hospital admission.  
3.2 ELIGIBILITY CRITERIA  
3.2.1 INCLUSION CRITERIA 
• 
Age ≥ 40 years 
• 
Individuals admitted to hospital with COPD exacerbation. Admission is defined as an episode in which 
a patient with an exacerbation of COPD is admitted to a ward and has stayed in hospital for 4 hours or 
more, including Emergency Medicine Centres, Medical Admission Units, Clinical Decision Units, 
short stay or virtual wards or similar but excludes patients treated transiently before being discharged 
from Emergency Department.  
• 
Ability to provide written informed consent. 
3.2.2 EXCLUSION CRITERIA  
• 
Individuals who require invasive ventilation during the hospital admission 
• 
Patients who have an expected survival of less than 90 days 
• 
Patients with signs of new consolidation on chest X-ray (if available)Individuals who have been discharged 
to residential or nursing home. 
• 
Individuals who are unable to manage a supported self-management plan. 
• 
Individuals with no access to telephone. 
• 
Individuals who are already taking part in an interventional trial. 
• 
Previous participation in the RAPID trial. 
3.3 IDENTIFICATION OF ELIGIBLE PARTICIPANTS  
Patients admitted to hospital with an exacerbation of COPD could be potential participants for recruitment into 
the study. While some controversy exists around pneumonic COPD exacerbations46, for the purposes of the 
trial, patients with COPD background and signs of consolidation on X-ray should be classified as diagnosed 
with pneumonia. At time of hospital admission, the direct clinical care team will identify potential participants 
admitted with COPD exacerbation and inform the study team who will then provide study information sheets 
at the earliest opportunity. This will all happen in the hospital setting.  In this study, as patients admitted with 
COPD exacerbations are routinely looked after by the respiratory team (respiratory consultants, respiratory 
trainee doctors, respiratory nurse team, respiratory pharmacist team, respiratory physiotherapists) 
identification of potential participants will be part of research practices for each site and direct and rapid 
communication with the study team is expected. The direct clinical care team will notify the study team of the 
following personal identifiable data: name, DOB, Hospital Number. If potential participants are interested in 
taking part, then the study team will be informed for potential recruitment. In scenarios where the patient is 
not admitted under the respiratory team, then the direct clinical care team will identify potential participants 
and ask if they are interested in taking part in the study; and if potential participants are interested in taking 
part, then the study team will be informed for potential recruitment. 
3.4 INFORMED CONSENT  
Informed consent must be obtained before any trial related procedures or assessments can be done. The 
participant will be given a copy of the Patient Information Sheet (PIS) and Informed Consent Form (ICF) and 
the investigator or designated person must ensure participants are informed about the trial, their participation 
and any associated risks. Consent will be taken by any suitably qualified person as delegated by the PI 
(including research nurses, clinical trial practiotioners, etc). The investigator will retain one copy of the original 

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signed consent forms for the investigator site file, a second copy will be given to the participant to keep and a 
copy will be uploaded to the participant’s medical records.   
 

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4. DATA COLLECTION & DATA ENTRY 
4.1 PARTICIPANT TIMELINE 
TABLE 1 SCHEDULE OF EVENTS  
*in relation to discharge from hospital; ¥ twice-weekly for 90 days in the intervention arm; ¶window for interviews +/- 14 days; § sub-
study; †resupply of rescue pack(s) if used within 90 day window.  
4.1.1 VISIT WINDOWS  
Telephone calls at 30 and 90 days will be +/- 3 days (one week window), with the day 180 and 365 calls 
+/- 7 days (two week window). 
Timepoint 
Screening 
 
Baseline (-3 
to 0 days)*  
Day 30 
+/- 3 
Day 90 
+/- 3 
Day 180 
+/- 7 
 
1 year 
+/- 7 
Ongoing  
1. Registration form & consent 
X 
 
 
 
 
 
 
2. Eligibility  
X 
 
 
 
 
 
 
3. Medical history  
X 
 
 
 
 
 
 
4. COPD history 
X 
 
 
 
 
 
 
5. Demographic data 
X 
 
 
 
 
 
 
Collation of routine investigations and 
and data on this admission eg LOS 
 
X 
 
 
 
 
 
Clinical Frailty Scale 
 
X 
 
 
 
 
 
The modified MRC Scale 
 
X 
 
X 
X 
X 
 
Dyspnea VAS 
 
X 
 
X 
X 
X 
 
6. Randomisation  
 
X 
 
 
 
 
 
7. Status form to include VITAL 
STATUS, 
READMISSIONS 
and 
COMMUNITY TREATED EXACS 
 
 
X 
X 
X 
X 
 
8.  Study Follow-Up Telephone call 
 
 
X 
X 
X 
X 
 
9.  EQ-5D-5L 
 
X 
 
X 
X 
X 
 
10. COPD Assessment Test (CAT) 
 
X 
 
X 
X 
X 
 
11.  Resource use questionnaire  
 
X 
 
X 
X 
X 
 
12. Text messaging/tel call¥  
 
 
X 
X 
 
 
 
13. Seriousadverse events log 
 
 
 
 
 
 
X 
14. Concomitant medications log 
 
X 
 
 
 
 
 
15. Withdrawal form 
 
 
 
 
 
 
X 
16.  Rescue packs dispensing 
 
X 
 
 
 
 
X† 
17. Interview¶§ 
 
 
 
X* 
 
 
 
18.  Biological sample collection 
(including 
stool, 
nasosorption, 
sputum)§ 
 
X 
 
X 
 
 
 

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4.1.2 SCREENING  
Patients will be identified and screened whilst in hospital before they are discharged.  
4.1.3 BASELINE  
Patients will be randomised following eligibility checks and consent. Baseline data will be collected as per 
the Schedule of Events in Table 1 prior to patient being discharged. 
Participants in the intervention arm will receive a rescue pack prior to being discharged from hospital. 
4.1.4 DAY 30, 90 AND 180 TELEPHONE CALLS 
Follow up data will be collected as per the Schedule of Events in Table 1 above. At each follow up 
timepoint, a status form is completed; in the event of a missed visit, the status form must be completed. 
The following will be collected: 
• 
Time to and frequency of all COPD-related readmissions  
• 
Time to and frequency of all COPD exacerbations 
• 
Time to first all cause readmission  
• 
Time to and frequency of COPD related readmissions  
• 
Days alive and out of hospital at 90 days 
• 
Cumulative oral corticosteroids and antibiotic use  
• 
Healthcare contacts 
• 
All cardiovascular and COPD related mortality 
• 
Use of secondary healthcare services 
• 
SAEs  
• 
Subject to optional consent, a qualitative telephone interview will be scheduled with a subsample 
of intervention-arm participants at approximately 90 days post-discharge (+/-14 days). For further 
details, see section 4.11 
In the event that the participant in the intervention arm uses the rescue pack within the first 90 days, a new 
pack will be provided by the research team. 
 
4.1.5 DAY 365 OR END-OF-STUDY TELEPHONE CALL 
Day 365 data will be collected as per the Schedule of Events in Table 1 above. In the event a participant wishes 
to stop the study and withdraw from further data collection, a withdrawal form must be completed. Where 
possible a withdrawal call should be scheduled to undertake a final set of outcome assessments. In cases where 
the participant completes the study to month  12, a withdrawal form should be completed at the final visit to 
indicate they never withdrew.   
The following data will be collected: 
• 
Healthcare contacts 
• 
Use of secondary healthcare services 
• 
All cardiovascular and COPD related mortality – to be collected over 12 months 
• 
SAEs  
 
4.1.6 TWICE WEEKLY TEXT MESSAGING/TELEPHONE  
In the intervention arm, Patients will receive twice weekly telephone calls or text messages for 90 days 
following randomisation. This will ask patients about their level of symptoms and remind patients that if 
there is a sustained increase in their symptoms consistent with an exacerbation, to use their education plan, 
consider using their rescue pack and to contact their usual clinical provider.  
 
Frequent repeated patient contact is believed to lead to  
•Earlier recognition of symptoms  
•Earlier intervention by appropriate use of rescue pack 
•Reduced severity of exacerbation  

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•Reduced rate of readmission 
• Earlier recognition of signs of exacerbation and knowledge of appropriate action 
 
4.2 DATA ENTRY  
Authorised staff at sites will transcribe baseline and follow up participant data from source data (SD) to the 
study eCRF by going to www.ctu.co.uk and clicking the link to access MACRO Version 4. A full audit trail 
of data entry and any subsequent changes to entered data will be automatically date and time stamped, 
alongside information about the user making the entry/changes within the system.  
Study site staff will be delegated by the site PI to access the eCRF and randomisation systems via a Study Site 
Delegation Log. The request for user access must go to the UK Trial Manager, who will submit user requests 
for all sites to the KCTU team upon receipt of completed Study Site Delegation Logs. Requests for user access 
will be processed within a maximum of 5 working days.  
Training videos for data entry staff, study site monitors and trial managers / trial co-ordinators are available at 
www.ctu.co.uk under the ‘Training’ section. Users can self-register and should select the MACRO related 
training videos.  
4.3 BASELINE DATA COLLECTION 
4.3.1 REGISTRATION  
When the participant has signed consent, the study site staff should register the participant in the MACRO 
eCRF system. Upon registration, the system will assign a unique study PIN, to be used for the participant 
throughout the study. 
4.3.2 ELIGIBILITY 
All eligibility checks must be completed and eligibility confirmed prior to randomisation.  
4.3.3 MEDICAL HISTORY 
Relevant medical history must be recorded. If the participant is taking any medications at baseline, the 
relevant condition should be recorded in the medical history.  
4.3.4 DEMOGRAPHICS 
Relevant demographic information will be collected prior to randomisation. This includes age, gender, 
ethnicity, smoking history and social/home situation. 
4.3.5 CLINICAL DATA  
Relevant data from the clinical episode, including blood tests, x-rays (where applicable), clinical frailty43, 
dyspnea VAS44, modified MRC45 scores, treatment and length of stay will be collected and entered into 
the eCRF.  
4.3.6 RANDOMISATION 
Sites must confirm in the eCRF system whether participants were randomised into the study or not. Age 
at randomisation will be entered in the eCRF. The randomisation procedure and access to the 
randomisation system is described in the trial specific procedures. 
4.4 EFFICACY DATA 
Participant self-report measures should ideally be completed in the absence of the caregiver. 

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4.4.1 MEASURE 1:COPD ASSESSMENT TEST 
The COPD Assessment Test (CAT) is an eight-item health status instrument in COPD that is used to 
quantify the impact of COPD on the patient’s health  
4.4.2 MEASURE 2: EQ-5D-5L 
The EQ-5D-5L28 is a validated and widely used generic measure used to collection patients’ health-related 
quality of life.  
4.4.3 MEASURE 3: RESOURCE USE QUESTIONNAIRE  
A resource use questionnaire27 will be used to collect patients’ use of primary healthcare services, social 
care services and out of pocket expenditure and their carers’ productivity losses.  
4.5 SAFETY DATA 
4.5.1 SERIOUS ADVERSE EVENTS  
During each assessment, participants will be asked about adverse events. All serious adverse events will 
be recorded in an ongoing serious adverse event log. Symptoms of disease progression need only be 
recorded if treatment is required or if the physician is concerned that the rate of progression is unexpected.  
4.5.2 CONCOMITANT MEDICATIONS 
During each assessment, participants will be asked about their current medication. All concomitant 
medication will be recorded in an ongoing concomitant medication log.  
4.5.3 WITHDRAWAL  
A withdrawal form must be completed in the event of participant death or where the participant has stopped 
taking study medication and is no longer prepared to provide any follow up data or have their caregiver or 
family doctor provide any follow up data. Where the participant has stopped study intervention but is still 
being followed for primary outcome data, a withdrawal form should not be completed, but a status update 
must be recorded in the eCRF every 3 months.   
4.6 LABORATORY DATA 
The results of any routine clinical blood results will be entered into the eCRF. Routine sputum antibiotic 
sensitivity collected data will also be stored in the eCRF at admission and at any readmission for assessment 
of AMR. In a sub-study of patients, stool samples will be collected at baseline prior to discharge from the 
index exacerbation and at 90 days to assess the effect of rescue packs on AMR rates. Assuming that the 
comparator group has less AMR than the intervention group, and 20% drop out, it is estimated that 34 patients 
from each study arm will need to be sampled and sequenced for antibiotic resistance genes (ARGs) to 
determine a clinically meaningful effect of rescue packs on AMR. The results of any routine nasal/throat swabs 
and nasal absorption will also be collected during the admission and discharge. 
4.7 MEASURES TO PROMOTE PARTICIPANT RETENTION  
There are no in person visits in this study and so we do not anticipate challenges with retention.  We will work 
flexibly with patients regarding scheduling of phone calls, sending reminders before-hand. 
4.8 QUALITATIVE SERVICE EVALUATION TO CHARACTERISE STANDARD-OF-CARE 
Reflecting patterns in the UK10 and notwithstanding NICE guidance, standard of care in the participating sites 
is likely to vary greatly. Understanding the nature and level of support offered as standard of care to participants 
will be essential to interpretation of results. To address this need, prior to the delivery of the study described 
in this protocol, we will undertake a service evaluation as part of a sub-study using qualitative interviews with 

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relevant healthcare staff (providers and commissioners) to characterise standard of care in participating sites 
prior to site initiation, to identify the key aspects of variation that may have a bearing on the primary and 
secondary outcomes, and to inform collection of participant-level data relating to these variations in the trial. 
We will supplement data from these interviews with information derived from local protocols, guidance and 
other documents. 
 
5. QUALITATIVE SUB-STUDY TO UNDERSTAND INTERVENTION DELIVERY 
The delivery of a complex intervention with several component parts such as rescue packs and their associated 
interventions including education and reminders, is subject to mutation at various points in the process. This 
may include appropriate adaptions of the intervention to local circumstances, and changes that are likely to 
undermine positive impact. Both to understand the impact of the intervention (and particularly variability in 
impact) and to equip practitioners to make the best use of it if adopted in routine care, it is important to 
understand the nature of those variations and the extent to which fidelity to the intervention as intended has 
been achieved. We will carry out interviews after the 90-day follow-up period with patients in the study’s 
intervention arm. We will seek a sub-sample that exhibits strong heterogeneity in characteristics that may 
affect participants’ attitudes towards and use of rescue packs and the associated package of supporting 
measures.  
As part of the consent process for the study, participants will be asked (optionally) to consent to being contacted 
by the study team regarding participation in an interview about experiences of the intervention at around 90 
days. Contact details of patients who give consent to this, will be collated on a monthly basis and passed to the 
qualitative research team, along with basic demographic details (site, sex, age, ethnicity, language, date of 
discharge), to inform identification of a subsample. At follow-up calls, the research team will address eligibility 
for, and agreement to undertake the qualitative interviews and pass contact details on to the qualitative research 
team.  The qualitative team will contact participants using the information provided at 90 days (+/-14 days). 
At this point, participants will have the chance to ask further questions about the study, and consent will be 
reaffirmed verbally; information sheets will be re-supplied upon request. Where a participant’s preferred 
language is not English, this contact will be supported by a professional interpretation service. The qualitative 
team will keep an ongoing record of participants who agree to be interviewed, with a view to securing variation 
in the following characteristics and constructing a diverse sample: 
• 
Gender 
• 
Age 
• 
Ethnicity 
• 
Preferred language 
• 
Site of recruitment 
 
As recruitment proceeds, the profile of the sample according to each of these variables will be kept under 
review, and further recruitment will be targeted at groups that are less well represented in the sample to date. 
Up to approximately 60 participants will be recruited across all sites (around two per site on average). 
 
Where participants agree to be interviewed, the researcher will agree an appropriate time and date for the 
interview. Interviews will be conducted by telephone, will take up to approximately 60 minutes, and will be 
audio-recorded using an encrypted device. They will follow a topic guide focusing on the participant’s 
experience of the post-discharge intervention, including their knowledge of the use of rescue packs, whether 
they used a rescue pack and in what circumstances, their views on the support and guidance provided (written, 
telephone, and text message), and the fit of the intervention into their day-to-day lives. Topic guides informed 
by constructs from the COM-B framework40 and from Burden of Treatment Theory41, with a view to 
understanding both the individual-level and social influences on reception and use of the rescue packs and 
associated support. 
 
Following completion of interviews, audio recordings will be moved to the University of Cambridge Safe 
Haven storage space, and then transferred securely to a professional transcription service with appropriate 
confidentiality and data-sharing agreements in place. In the course of transcription, identifying features will 
be anonymised. Anonymised transcripts will be returned to the Safe Haven, at which point they will be checked 

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against audio recordings to ensure full anonymity and accuracy. Once this has been verified, audio recordings 
will be destroyed the anonymous transcripts will then be transferred from the University of Cambridge Safe 
Haven to the University of Cambridge research drive for analysis. Analysis will be based on the constant 
comparison approach, adapted to incorporate sensitising concepts from COM-B and Burden of Treatment 
theory, and will focus in particular on: (i) the impacts of participants’ diverse backgrounds and circumstances 
on their attitudes towards and use of the rescue packs and other components of the intervention; (ii) the 
consequences for adherence to intended use; and (iii) the implications for refining protocols for administering 
rescue packs and supporting resources and how these might best be tailored to individual patients’ situations.  
 
6. INTERVENTIONS 
6.1 EXPLANATION FOR THE CHOICE OF COMPARATORS  
The comparator is usual care, which will vary by site, and will be studied via a qualitative sub-study.  
6.2 INTERVENTION AND COMPARATOR DESCRIPTION, DOSING AND LABELLING 
The intervention arm consists of 3 components: i) a written (and/or translated) management plan for COPD 
exacerbations as per Asthma+Lung UK; ii) medication in the form of a rescue pack and iii) reminder text or 
telephone messages, twice per week as per section 4.1.6. A ‘rescue pack’ according to local prescribing 
guidelines, will be allocated to the intervention arm. This typically consists of 5-7 days of prednisolone (30mg 
to be taken once a day) and 5-7 days of amoxicillin (500mg to be taken three times a day). If participants in 
the intervention arm use their rescue packs a further rescue pack will be provided by the study team, up to 90 
days following randomisation. The control study arm will not receive a rescue pack on randomisation, by the 
study team. However, participants in the control study arm may have access to rescue packs in the community, 
their homes or their community care team for which we will record this use on study visit telephone calls.   
7. ASSIGNMENT OF INTERVENTIONS 
7.1 RANDOMISATION METHOD 
The method of randomisation in the trial is stratified randomisation with two stratifiers defined by COPD 
hospitalisations (severe exacerbation) in the last year and previous exacerbations (moderate or severe) in the 
last year and (excluding the index hospitalisation). 
I) 
Prior versus no prior severe exacerbations in the last year  
II) 
>=2 or <2 moderate/severe exacerbations in the last year 
 
Randomly permuted blocks will be used within the four strata defined by the categories of these stratifiers. 
 
Severe exacerbation is defined as a COPD exacerbation requiring hospitalisation, moderate exacerbation is 
defined as a COPD exacerbation that is treated with steroids and/or antibiotics, but that does not require 
hospitalisation. 
 
7.2 RANDOMISATION IMPLEMENTATION  
7.2.1 ALLOCATION SEQUENCE GENERATION 
The randomisation sequence will be generated dynamically by the KCTU team via the KCTU web based 
randomisation system, in accordance with the specification agreed with the CI and Senior Statistician. The 
Chief Investigator, Senior Statistician and TMG will be blinded to the sequence generation.  

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7.2.2 ENROLMENT OF PARTICIPANTS 
Participants will be enrolled in the study for the purpose of CONSORT reporting at the point of signing a 
consent form to being screened for eligibility and will be part of the target N=1400 at the point of 
randomisation. 
7.2.3 ASSIGNMENT OF PARTICIPANTS TO INTERVENTIONS  
Recruiting sites will assign participants to interventions by logging into the ‘KCTU randomisation and 
IMP management system’ at www.ctu.co.uk (click ‘randomisation’ and select ‘XXXX study) and 
entering the participant’s year of birth and age and stratifiers.  
8. LABORATORIES 
8.1 SAMPLE COLLECTION 
In participants who provide consent, stool and nasal fluid samples for exploratory analysis will be collected at 
baseline prior to discharge and at 90 days. These samples will be collected by sites and in bulk will be 
transported for laboratory analysis to University College London (UCL) for stool and to King’s College 
London (KCL) for nasal fluid. Samples will be stored in -20C or -80C freezers.  
8.2 SAMPLE ANALYSIS PROCEDURES 
All processed samples will be cell-free and not have any human genetic material. Stool samples will be 
analysed to understand anti-microbial resistance, including measurement of antibiotic resistance genes. Nasal 
fluid samples will also be analysed to measure inflammatory proteins, including chemokines and cytokines.  
 
8.3 SAMPLE DATA RECORDING 
As exploratory data, results will be recorded in a safe password controlled held spreadsheet at UCL and 
KCL.  
8.4 SAMPLE INCIDENTS 
As this is a sub-study with exploratory analysis, any incidents of sample handling or loss will not be required 
to be reported to the sponsor. Incidents of sampling handling or loss will be reported according to local 
guidelines as part of standard practice.  
Sample incidents taking place at the Guy’s and St Thomas’ NHS Foundation Trust should also be reported 
on the Trust risk register Datix: http://gti.gstt.local/services/healthsafety/health-safety-main-pages/i-am-
interested-in/accidents-and-incidents-reporting.aspx 
9. DATA MANAGEMENT 
9.1 DATA MANAGEMENT  
There are two datasets in the trial: the KCTU randomisation dataset and the KCTU Elsevier Macro 4 eCRF 
system dataset. Source data worksheets will be supplied to all recruiting sites by the co-ordinating centre for 
the region. These will be prepared after the database specification is finalised and database testing is complete. 
Laboratory results may be reviewed directly in hospital laboratory systems where appropriate and need not be 
transcribed in full to the source data work. The source data worksheet must confirm that the samples were 
processed, and any abnormal results must be recorded and transcribed. Normal results need not be transcribed. 
Data will be transcribed from the source to the MACRO eCRF system, ideally within 7 days of the study visit. 
Participating Sites will complete source data location lists defining the source data at their site. The CI will act 
as custodian for the trial data. The flow of trial data is outlined in Figure 1. 

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§.  
 
Figure 1. Data Flow  
9.2 DATA SECURITY  
Clinical trial will involve the sharing of deidentified data and samples of subjects for research purposes, both 
during and after the trial for the purposes of monitoring and analysis. All applicable statutory requirements and 
mandatory codes of practice in respect of confidentiality (including, where applicable, medical confidentiality) 
in relation to such trial subjects or their legal guardians. Data flow will be governed by UK-specific 
requirements. 
Data Management Plans will be provided to the Trial Manager, detailing relevant security information about 
both data systems. Systems access will be strictly restricted through user-specific passwords to the authorised 
research team members. It is a legal requirement that passwords are not shared, and that only those authorised 
to access the system are allowed to do so. If new staff members join the study, a user-specific username and 
password must be requested and a request for access to be revoked must be requested when staff members 
leave the project.  
Participant year of birth and age will be entered into the systems. No more identifiable data will be entered 
into the eCRF system. Trial sites will maintain a master participant log linking participant identifiers to study 
numbers. No data will be entered unless a participant has signed a consent form to participate in the trial 

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9.3 DATA QUALITY PROCESSES  
At the database design stage, validations will be programmed into the systems to minimise data entry errors 
by querying the data entered in real time with sites.  
The CI team will undertake appropriate reviews of the entered data, in consultation with the project analyst, 
where appropriate for the purpose of data cleaning and will request amendments to the MACRO eCRF system 
data as required. No data will be amended independently of the study site responsible for entering the data. 
No data can be amended in the randomisation system, however CI or delegate (e.g., Trial Manager) may 
request King’s Clinical Trials Unit to add notes against individual participant entries to clarify data entry errors. 
Any errors should be reported by site staff to the Trial Manager as soon as possible once they are detected. 
The trial manager will onward report errors to KCTU and retain records in the TMF. 
The KCTU will provide the Trial Manager with Data Management Plans for both the Elsevier Macro eCRF 
system and the randomisation system once the systems are made live. Those documents will be filed in the 
Trial Master File. 
A regular Data Management Report will be produced by KCTU and passed to the Trial Manager, who will 
raise Data Clarification Requests (DCRs) with sites in the eCRF system. The Trial Manager will raise DCR’s. 
Study sites will periodically review raised DCR’s and respond to the queries raised.  
During site monitoring visits, the Trial Manager  will raise any queries with sites via the Source Data 
Verification (SDV) function.  
9.4 DATABASE LOCK  
At the end of the trial, the site PI’s will review all the data for each participant in the MACRO eCRF system 
and provide electronic sign-off to verify that all the data are complete and correct.  
The trial manager will confirm all checks are complete and all monitors queries have been resolved prior to 
database lock. At this point, with the agreement of the senior statistician, all data can be formally locked for 
analysis.  
When the final data extract is requested, KCTU will remove all data entry user access prior to data extract and 
will retain only ‘monitor’ access for site PI’s and other relevant individuals.  
Upon request, KCTU will provide a copy of the final exported dataset to the CI in .csv format and the CI will 
onward distribute to sites as appropriate. Once sites have received copies of their individual datasets and 
confirmation of receipt has been received, the Trial Manager will request that all user access is removed from 
the MACRO eCRF system. A copy of the dataset will be stored in the TMF at the end of the study. 
 
10. SUMMARY OF KNOWN AND POTENTIAL RISK OF RESCUE PACKS 
Administration of rescue packs for this study is not anticipated to induce any potential risk other than the 
known potential side effects as listed in the British National Formulary (BNF).  
Undesirable effects of prednisolone 
A wide range of psychiatric reactions including affective disorders (such as irritable, euphoric, depressed and 
labile mood, and suicidal thoughts), psychotic reactions (including mania, delusions, hallucinations, and 
aggravation of schizophrenia), behavioural disturbances, irritability, anxiety, sleep disturbances, and cognitive 
dysfunction including confusion and amnesia have been reported. Reactions are common and may occur in 
both adults and children. In adults, the frequency of severe reactions has been estimated to be 5-6%. 
Psychological effects have been reported on withdrawal of corticosteroids; the frequency is unknown. The 

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incidence of predictable undesirable effects, including hypothalamic-pituitary adrenal suppression correlates 
with the relative potency of the drug, dosage, timing of administration and the duration of treatment (see 
Section 4.4 'Special warnings and special precautions for use').   
  
11. ADVERSE EVENT MANAGEMENT AND REPORTING 
All serious adverse events will be recorded in the participants medical notes, the study source data worksheets, 
and the eCRF. SAE’s will be additionally reported, within 24 hours of site becoming aware of the event, to 
KCTU.  
All SAEs, SARs and SUSARs (except those specified in this protocol as not requiring reporting) will be 
reported immediately (and certainly no later than 24hrs) as per the instructions on the SAE report form.  
In research other than CTIMPs, a Serious Adverse Event (SAE), Serious Adverse Reaction (SAR) or Suspected 
Unexpected Serious Adverse Reaction (SUSAR) is defined as any adverse event, adverse reaction or 
unexpected adverse reaction, respectively, that: 
o results in death 
o is life-threatening 
o required hospitalisation or prolongation of existing hospitalisation 
o results in persistent or significant disability or incapacity 
o consists of a congenital anomaly or birth defect 
o is otherwise considered medically significant by the investigator 
An SAE occurring to a research participant should be reported to the main REC (the REC that gave favourable 
opinion of the study) where in the opinion of the Chief/Principal Investigator the event was: 
o “Related” – that is, it resulted from administration of any of the research procedures, and  
o “unexpected” – that is, the type of event is not listed in the protocol (section10)/BNF as an expected 
occurrence. 
The Chief/Principal Investigator or Sponsor must submit reports of related and unexpected SAEs within 15 
days of the Chief/Principal Investigator becoming aware of the event, using the SAE report form for non-
CTIMPs available from: https://www.hra.nhs.uk/approvals-amendments/managing-your-approval/safety-
reporting/ 
Important Medical Events (IME) & Pregnancy: Events that may not be immediately life-threatening or result 
in death or hospitalisation but may jeopardise the participant or may require intervention to prevent one of the 
other outcomes listed in the definition above should also be considered serious. Although not a serious adverse 
event, any unplanned pregnancy will also be reported via the SAE reporting system. 
11.1 EVALUATING SAES 
11.1.1 ASSESSMENT OF INTENSITY  
The Investigator will make an assessment of intensity for each SAE reported during the study. The 
assessment will be based on the Investigator’s clinical judgement. The intensity of each SAE recorded in 
the eCRF should be assigned to one of the following categories: 
o Mild; An event that is easily tolerated by the participant, causing minimal discomfort and not 
interfering with everyday activities 
o Moderate; An event that is sufficiently discomforting to interfere with normal everyday activities 
o Severe; An event, which is incapacitating and prevents normal everyday activities 

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An AE that is assessed as severe should not be confused with an SAE. Severity is a category utilised for rating 
the intensity of an event; and both AEs and SAEs can be assessed as severe. 
11.1.2 ASSESSMENT OF CAUSALITY 
The Investigator is obligated to assess the relationship between intervention and the occurrence of each 
SAE. The Investigator will use clinical judgment to determine the relationship. Alternative causes, such 
as natural history of the underlying diseases, concomitant therapy, other risk factors, and the temporal 
relationship of the event to the investigational product will be considered and investigated.  
The causal relationship to the study procedures assessed by the Investigator (or medically qualified 
delegate) should be assessed using the following classifications: 
o Not Related: In the Investigator’s opinion, there is not a causal relationship between the study 
intervention and the SAE. 
o Unlikely: The temporal association between the SAE and study internevtion is such that the study 
intervention is not likely to have any reasonable association with the SAE. 
o Possible: The SAE could have been caused by the study participant’s clinical state or the study 
intervention. 
o Likely: The SAE follows a reasonable temporal sequence from the time of study intervention 
administration, abates upon discontinuation of the study intervention and cannot be reasonably 
explained by the known characteristics of the study participant’s clinical state. 
o Definitely: The SAE follows a reasonable temporal sequence from the time of study intervention 
administration or reappears when study interventionis reintroduced. 
There may be situations when an SAE has occurred, and the Investigator has minimal information to 
include in the initial report to the Sponsor. However, it is very important that the Investigator always 
assesses causality for every event prior to transmission of the SAE form to the Sponsor. The Investigator 
may change his/her opinion of causality considering follow-up information, amending the SAE form 
accordingly. The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
11.1.3 ASSESSMENT OF EXPECTEDNESS 
A reasonable possibility of a relationship conveys that there are facts, evidence and/or arguments to suggest 
a causal relationship, rather than a relationship that cannot be ruled out. 
o Expected: An adverse reaction, the nature or severity of which is consistent with the applicable 
Reference Safety Information in the Summary of Product Characteristics for an approved medicinal 
product 
o Unexpected: An adverse reaction, the nature or severity of which is not consistent with information in 
the relevant source document 
11.1.4 FOLLOW-UP OF SAES 
After the initial SAE report, the Investigator is required to proactively follow each participant and provide 
further information to the Sponsor on the participant’s condition. All SAEs documented at a previous 
visit/contact and are designated as ongoing, will be reviewed at subsequent visits/contacts. All SAEs will 
be followed until resolution, until the condition stabilises, until the event is otherwise explained, or until 
the participant is lost to follow-up. Once resolved, the adverse event log will be updated. The Investigator 
will ensure that follow-up includes any supplemental investigations as may be indicated to elucidate the 
nature and/or causality of the SAE. This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other health care professionals. New or updated 

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information will be recorded on the originally completed SAE form, with all changes signed and dated by 
the Investigator. The updated SAE form should be resent to the Sponsor. 
11.1.5 POST-STUDY SAES 
A post-study SAE is defined as any event that occurs outside the SAE detection period. Investigators are 
not obligated to actively seek SAEs in former study participants. However, if the Investigator learns of 
any SAE, including death, at any time after a participants has been discharged from the study, and he/she 
considers the event reasonably related to the investigational product, the Investigator will promptly notify 
the Sponsor. 
11.1.6 SAES  
SAEs that lead to hospitalisation within 90 days of randomisation will be source data for the primary 
endpoint and will detail cause of hospitalisation to determine if this was related to COPD or not.  
 
11.2 ADVERSE EVENT PROCESSING RESPONSIBILITIES 
The Trial Statistician will report relevant adverse events to the Data Monitoring Committee.  
 
12. ETHICS APPROVAL 
This protocol and related documents will be submitted for review to Health Research Authority (HRA), and 
Research Ethics Committee (REC). 
12.1 PROTOCOL AMENDMENTS AND VERSION CONTROL OF STUDY DOCUMENTS  
The Trial Manager will be responsible for preparing and submitting protocol amendments to the Sponsor and 
ethics committee/HRA.   
TheTrial Manager will be responsible for updating the ISRCTN register subsequent to relevant protocol 
amendments. 
13. STATISTICAL METHODS 
13.1 PRIMARY OUTCOME  
1. Time to first all-cause readmission within 90 days of discharge from hospital. The day of discharge 
will be the 1st day in the countdown to 90-day timepoint 
13.2 SECONDARY OUTCOMES  
• 
Time to and frequency of COPD-related readmissions at 30 and 90 days 
• 
Days alive and out of hospital at day 90 
• 
Time to and frequency of all COPD exacerbations at days 30 and 90 
• 
Cumulative systemic oral corticosteroids use over 90 days, measured as proportion of period used and 
number of occasions used 
• 
Cumulative systemic antibiotic use over 90 days, measured as proportion of period used and number of 
occasions used 
• 
Health care contacts at baseline, days 90 and 180, and 1 year 
• 
All cause readmission at 30 days 

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• 
All cause-, cardiovascular- and COPD- related mortality at day 90 and over 12 months 
• 
Quality of life (COPD assessment Test (CAT) score and EQ-5D-5L) at baseline, days 90 and 180, and 1 
year 
• 
Incremental cost-effectiveness ratio (ICER, a ratio of the additional cost divided by the additional 
effectiveness of SRP compared to UC) at days 90 and 180 and 1 year 
• 
Qualitative description of usual care 
• 
Qualitative examination of fidelity to and adaptation of the plan in the intervention arm 
• 
Serious adverse events 
• 
Antimicrobial resistance 
 
13.3 SAMPLE SIZE JUSTIFICATION 
A sample size of 1400 participants randomised has been chosen to achieve a target of 515 primary outcome 
events. Population estimates of the 90-day and 30-day all-cause readmission rates of 43% and 
23%42respectively have been reported previously. In the absence of a minimum clinically important effect size 
defined for the 90-day all-cause readmisstion primary outcome, we performed a national survey of respiratory 
COPD secondary care specialists via the British Thoracic Society, with responses from 80 participants. This 
supported a 20% relative reduction as the minimum required to be considered clinically meaningful. This 
corresponds to an intervention arm readmission rate of 34.4%. As the 30-day and 90-day rates are not 
consistent with an exponential time-to-event survival distribution, the log rank test was chosen for the sample 
size and the primary analysis. With 515 first readmission events, there is 90% power to detect a reduction from 
43% to 34.4% in the 90-day reasdmission rate using a two-sided log rank test at the 5% level of significance 
and 1:1 allocation to the goups. In the absence of withdrawals, 1331 participants would be required. This was 
inflated to a sample size of 1400 participants randomised, representing a 5% participant withdrawal rate, and 
this is expected to maintain the target of 515 events. The randomisation is stratified but the primary analysis 
will use the log rank test, for simplicity and to match the sample size calculation, as the purpose of the stratifiers 
is predominantly as foundation for subgroup analyses given that the large sample size limits chance 
confounding effects. 
 
13.4 STATISTICAL METHODS FOR PRIMARY AND SECONDARY OUTCOMES  
13.4.1 STATISTICAL METHODS FOR PRIMARY OUTCOME 
The log-rank test will be used to test the null hypothesis of no difference in readmission-free survival 
distributions between arms at the two-sided 5% significance level. These data will be collected primarily from 
HES. If HES data is not available, then other sources of data will be used (patient-reported data, SAE forms). 
These distributions will be described using the Kaplan-Meier plot. The univariate Cox proportional hazards 
model will be used to estimate the unadjusted hazard ratio with 95% confidence interval. In our previous meta-
analysis, comorbidities, previous exacerbations and hospitalisation, and increased length of stay were 
significant risk factors for 30-day and 90-day all-cause readmission after an index hospitalisation with an 
exacerbation of COPD. Chance confounding effects are not expected given the planned size of the trial and 
the number of events. We will however secondarily adjust for the randomisation stratifiers as main effects 
within the Cox model framework. This model will be extended to  explore the consistency of the primary 
outcome result across categories of the randomisation stratifiers, and other subgroup variables defined in the 
statistical analysis plan. This will involve including the interaction of a subgroup variable with study arm, 
Randomised controlled intervention effects within subgroup categories will be estimated with 95% confidence 
intervals. 

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We will seek to idenstify an appropriate survival distribution, in order to favilitate the development of predicted 
probabilities of readmission and to estimate key readmission duration quantiless. The proportionality of 
hazards assumption will be assessed using recommended methods26. The noninformative censoring 
assumption will be assessed in a sensitivity analysis, where the censoring of the 90-day all-cause first 
readmission, by a COPD-related death, is dealt with as a composite outcome. Departures from assumptions, 
and consequently required analysis methods will be desribed in the statistical analysis plan.  
Survival analysis methods will be used for the outcome of the number of days alive and out of hospital at day 
90I, which may be censored, and for other time-to-event secondary outcomes. Strategies to minimise missing 
data include obtaining primary outcome dates from more than one source, capturing this in those who move 
outside the study area, and our PPI group having assessed questionnaire burden. Study dropout, and loss of 
events, are expected to be at most 5%. 
13.4.2 STATISTICAL METHODS FOR SECONDARY OUTCOMES 
13.4.2.1 CONTINUOUS OUTCOMES 
In secondary continuous outcome analyses, each randomisation stratifier and the baseline of the outcome, will 
be analysed as a main effect covariate and, if necessary, using the missing indicator method. Each repeated-
measures continuous outcome timepoint will be analysed using linear mixed effects models with unstructured 
correlation structure and with covariates, including arm, interacted with time. This beneficially includes partial 
responses of the outcome over time because the estimated correlations between the repeated measures act 
equivalently to impute missing responses applying a “missing at random” assumption given the data included 
in the model. As nonresponse could instead be “not missing at random”, the impact of this assumption will be 
investigated according to available collected reasons for withdrawal and missing responses, by means of 
sensitivity analysis in all randomised participants across a realistic range of values for the intervention effect 
amongst non-responders.  Details of these, and any sensitivity analyses, will be described in the approved 
statistical analysis plan. 
13.4.2.2 BINARY OUTCOMES 
Distinct from time-to-event outcomes, binary outcomes will be analysed between groups primarily as a 
difference in proportions. Methods for obtaining 95% confidence intervals will be reported in the statistical 
analysis plan.  
13.5 INTERIM ANALYSES (STATISTICAL) 
 No formal interim analysis is planned. An internal pilot phase will assess trial parameters but not the between-
arm effectiveness measures.The DMC will provide advice to the TSC, who will advise the Sponsor in making 
the final decision on continuing or stopping the trial. 
13.6 METHODS FOR PRE-SPECIFIED SUBGROUP ANALYSES 
Below are details of two pre-specified sub-group variables:  
i) 
Prior versus no prior severe exacerbations  in the last year (excluding the index exacerbation)  
ii) 
>=2 or <2 moderate/severe exacerbations in the last year (excluding the index exacerbation)  
 
The hypothesis is that the first category of each of these subgroup variables is related to worse outcomes, 
more precisely a higher rate of hospital re-admission. The subgroup analysis will investigate the consistency 
of the randomised intervention effect on the primary outcome analysis across these subgroup categories. 
 
13.7 METHODS TO HANDLE MISSING DATA 

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Our primary outcome (re-admission within 90 days of discharge from hospital) will be collected from source 
documentation of SAEs and HES Linkage data which is a robust method of data collection. Missing data from 
HES Linkage may arise from participants that have not consented for HES linkage to occur. Our experience is 
that this will be minimal, but to manage this, we will also collect directly from patients this information at 30 
and 90 days, using pre-specified questionnaires completed by the local site or central study coordinator at the 
lead site and SAE forms. For the majority of our secondary outcomes, we will be using HES linkage data, 
which will minimise missing data. Data will be linked via a third party using NHS number. No NHS numbers 
will leave the NHS, instead unique study IDs will be used and data will be stored in the Safe Haven at King’s 
College London. Named researchers will have virtual desktop infrastructure (VDI) access to log in and analyse 
the data as appropriate. For other secondary outcomes, including Health Economic analysis we will be using 
questionnaires collected over 4 timepoints. For missing EQ-5D index values at baseline, we will use mean 
imputation to fill in each missing index value independent of the treatment arm. We will follow the same 
approach for the total and different categories of costs at baseline. For missing EQ-5D index values at all 
follow up points, we will assume that the data are missing at random (MAR). We will replace the missing 
observations with a set of imputed values through multiple imputations drawn from posterior predictive 
distribution given the missing observed data31. For missing cost data at all follow up points, we will impute 
at the costs level using the same approach outlined for dealing with missing EQ-5D index values at follow up. 
We have limited questionnaires to the EQ-5D-5L and resource use questionnaire and the COPD assessment 
tool. These have been selected and prioritised to reduce burden of questionnaires to manage missing data. We 
have discussed this questionnaire limits with PPI and this was agreed that this design would reduce missing 
data, whilst not being overburdensome to patients and their carers. 
13.8 PLANS TO GIVE ACCESS TO THE FULL PROTOCOL AND PARTICIPANT LEVEL-DATA  
It is anticipated the full protocol and all results will be available as open access according to the rules of the 
funding bodies.  
13.9 HEALTH ECONOMIC ANALYSIS 
A cost-utility analysis will be conducted to compare the cost-effectiveness of the self-supported rescue pack 
intervention at day 90, 180 and one-year. In line with the recommendation of National Institute for Health and 
Care Excellence (NICE), a healthcare and societal costing perspective will be adopted34. The primary outcome 
of the economic analysis will be total cost per patient, total quality-adjusted life-years (QALYs) per patient, 
and incremental cost-effectiveness ratio (ICER). Interventions with an ICER less than £20,000-30,000 per 
QALY are considered cost effective. 
 
Data collection: Patients’ use of secondary healthcare services will be collected from the trial and the HES 
database. Patients’ use of primary healthcare services, social care services, their productivity losses and their 
carers’ productivity losses will be collected using a resource use questionnaire adapted from a previous UK 
RCT35 for patients with COPD at baseline, days 90, 180 and 1 year. For all health and social care services, 
nationally applicable unit costs will be taken from the annual Personal Social Services Research Unit (PSSRU) 
compendium. National Health Service reference costs and national tariffs will be used to estimate the cost of 
inpatient, accident and emergency and day hospital attendances where necessary. Cost of steroid medicines, 
antipsychotic medications and other drugs will be calculated using daily dose information and the cost of the 
generic drugs as listed in the British National Formulary (BNF). EQ-5D-5L36, a validated and widely used 
generic measure will be used to collect patients’ health-related quality of life data. Both the EQ-5D-5L and 
resource use questionnaire will be administered at baseline, days 90, 180 and 1 year.   
Missing data: For missing EQ-5D index values at baseline, we will use mean imputation to fill in each missing 
index value independent of the treatment arm37. We will follow the same approach for the total and different 
categories of costs at baseline. For missing EQ-5D index values at all follow up points, we will assume that 
the data are missing at random (MAR). We will replace the missing observations with a set of imputed values 
through multiple imputations drawn from posterior predictive distribution given the missing observed data38. 
For missing cost data at all follow up points, we will impute at the costs level using the same approach outlined 
for dealing with missing EQ-5D index values at follow up.   

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Analysis: The utility scores derived from EQ-5D will be used to calculate QALY accrued over the follow-up 
period using area-under-the-curve methods and assuming a linear change between any two adjacent time 
points. Costs will be calculated using data on the type, number and length of contacts received by each 
participant. No discounting is needed as the maximum time horizon of the economic analysis is one year. 
Uncertainty of the results will be quantified by bootstrapping and reported as the cost-effectiveness planes and 
cost-effectiveness acceptability curve (CEAC)39. Cost-effectiveness planes plot the adjusted mean differences 
in total cost and QALYs based on the bootstrapped results. The CEAC curve will be derived by calculating 
the proportion of bootstrapped estimates that are cost-effective across a range of willingness-to-pay thresholds, 
to show the probability that the intervention is cost-effective across different threshold values. A Health 
Economic Analysis Plan (HEAP) will be developed which will describe their plans in more detail. 
14. OVERSIGHT AND MONITORING  
14.1 TRIAL MANAGEMENT GROUP (TMG) 
TABLE 4 TRIAL MANAGEMENT GROUP MEMBERSHIP IN RAPID STUDY 
Members of the TMG are listed in Table 4 above. Changes in individuals filling these roles will not require a 
protocol update but will be documented in the TMG minutes.  
14.2 TRIAL STEERING COMMITTEE (TSC) 
The TSC will be composed of a majority of independent members. The TSC is an executive committee, 
reporting to the funder (NIHR) and the sponsor. The TSC is formally appointed by NIHR and members will 
receive individual letters from NIHR confirming their role. Independent members will be independent of the 
Sponsor organisations and of any recruiting study sites.  
The trial may be prematurely discontinued by the Sponsor, Chief Investigator or Regulatory Authority on the 
basis of new safety information or for other reasons given by the Data Monitoring Committee / Trial Steering 
Committee regulatory authority or ethics committee concerned. 
If the trial is prematurely discontinued, active participants will be informed, and no further participant data 
will be collected. The Competent Authority and Research Ethics Committee will be informed within 15 days 
of the early termination of the trial. 
14.3 DATA MONITORING COMMITTEE (DMC)  
The DMC will be composed of three independent members: a statistician and two clinicians. The DMC is an 
advisory committee, reporting to the Trial Steering Committee. The DMC is formally appointed by NIHR and 
Title 
Name 
Role 
KCL Chief Investigator  
Mona Bafadhel 
Co-Chair 
UCL Academic co-lead  
John Hurst 
Co-Chair 
Senior Statistician  
Toby Prevost 
Member 
Trial Statistician  
Joana Carvalho Vasconcelos  
Member 
Health Economist 
Huajie (Lily) Jin 
Member 
KCTU Trial Manager (UK) 
Olena Said 
Member 
KCTU Trial Manager (UK) 
Stephen Lisk 
Member 
KCTU Operations Director (UK)  
Caroline Murphy 
Member 
KCTU Data Centre Lead (UK) 
Joanna Kelly 
Member 
Participant Representative (UK) 
Anna Goodman 
Observer 

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members will receive individual letters from NIHR confirming their role. Members will be independent of the 
Sponsor organisations and of any recruiting study sites. The DMC will work to the DAMOCLES guidance(39).  
14.4 MONITORING 
The Investigator(s) will permit trial-related monitoring, audits, REC review, and regulatory inspections by 
providing the Sponsor(s), Regulators and REC direct access to source data and other documents (e.g., 
participants’ case sheets, blood test reports etc.). The routine site monitoring activities will be performed 
remotely by the Trial Manager.  
15. MISCELLANEOUS  
15.1 PLANS FOR INDEPENDENT AUDIT 
There are no current plans to commission an independent audit of study conduct.  
15.2 DISSEMINATION PLANS  
The primary and secondary outcomes will be published in a peer reviewed open-source medical journal within 
12 months of the end of trial. Recruiting sites will be informed of the results and will be asked to disseminate 
the findings to participants. Patient groups will be informed of the results for dissemination among their 
members.  
15.3 END OF TRIAL 
The end of the trial will be defined as database lock.  
15.4 CONFIDENTIALITY  
When consent forms are signed, a copy will be provided to the participant, a copy will be filed in the medical 
records and the original will be retained in the Investigator Site File. Participant’s year of birth and age will be 
entered into the study database from countries where this is permitted, but no more identifying information 
will be collected outside the recruiting study site.  Within site, an Investigator Site File will be maintained by 
the site PI. Participants will be fully identifiable within these files.  
When the study is complete, a data sharing dataset will be created from the raw data by the study analyst, 
which will not include any other identifiable data and study PIN will be altered so that individuals are not 
recognisable from the dataset.   
The study will comply with the General Data Protection Regulations (GDPR). 
15.5 FUNDING  
This study has been funded by the NIHR HTA (application NIHR156698). 
15.6 INSURANCE AND INDEMNITY 
This study is co-sponsored by King’s College London (KCL) and Guys and St Thomas’ NHS Foundation Trust 
(GSTFT). The co-sponsors will, at all times, maintain adequate insurance for the design, management and 
conduct of the study: (a) KCL through its’ own professional indemnity (Clinical Trials) & no fault 
compensation policy; and (b) GSTFT through NHS Resolution cover, in respect of any claims arising as a 
result of negligence by its employees, brought by or on behalf of a study participant. 
15.7 ARCHIVING 
Upon request, KCTU will provide a copy of the final exported dataset to the CI in .csv format and the CI will 
distribute as appropriate for the purpose of archiving. The CIs will appoint named individuals within the 

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research team to be responsible for archiving the documents which are, or have been, contained in the trial 
master file and, access to those documents shall be restricted to those appointed individuals. At the end of the 
trial, all trial data will be stored and archived in line with Sponsor requirements. 
 
15.8 DATA CONTROLLER 
Guy’s and St Thomas’ NHS Foundation Trust (GSTFT) and King’s College London (KCL) as co-sponsors of 
the research study have shared Data Controller responsibilities and agree to comply with the Data Protection 
Legislation including UK GDPR. The data generated in the process of the study will flow into KCL and no 
data flow outside of KCL will occur. 
Where optional samples have been collected (samples containing no human tissue, cells or DNA), they may 
be stored and used for further research purposes according to the appropriate research protocols and with 
relevant material/data transfer agreements in place. 
 
15.9 INTELLECTUAL PROPERTY (IP) 
There will be no IP generated as a result of the study. 
 
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exacerbations of COPD. ERJ Open Res 2020;6. 
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5. Zhang Y, Morgan RL, Alonso-Coello P, et al. A systematic review of how patients value COPD outcomes. 
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15. King J, Arnold R, Russell R, Bafadhel M. Early discharge COPD experience: Reduction of severe 
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