Clinical Effectiveness of Pre-operative Cardiopulmonary Exercise Testing (CPET) in Predicting Post-operative Morbidity and Mortality After Pancreatoduodenectomy- A Retrospective Cohort Study
Conditions: Pancreas Cancer, Periampullary Carcinoma
Sponsor: East Lancashire Hospitals NHS Trust

FULL/LONG TITLE OF THE STUDY 
EFFECTIVENESS OF PRE-OPERATIVE CARDIOPULMONARY EXERCISE TESTING IN PREDICTING POST-
OPERATIVE MORBIDITY AND MORTALITY AFTER PANCREATODUODENECTOMY – A RETROSPECTIVE 
COHORT STUDY 
 
SHORT STUDY TITLE / ACRONYM 
THE ROLE OF PRE-OPERATIVE CPET IN PANCREATODUODENECTOMY 
RESEARCH REFERENCE NUMBERS 
IRAS Number: 284565 
SPONSORS Number: NONE 
FUNDERS Number:  NONE               
Document submitted to HRA/IRAS  Date: 11-12-2020 
Amendments:  
Document amended on 21-09-2023 for submission to Clinicaltrials.gov 
Document amended again on 28-09-2023 for submission to Clinicaltrials.gov 
 
                                    

STUDY SUMMARY 
Study Title 
EFFECTIVENESS OF PRE-OPERATIVE 
CARDIOPULMONARY EXERCISE TESTING IN PREDICTING 
POST-OPERATIVE MORBIDITY AND MORTALITY AFTER 
PANCREATODUODENECTOMY – A RETROSPECTIVE 
COHORT STUDY 
Internal ref. no. (or short title) 
THE ROLE OF PRE-OPERATIVE CPET IN 
PANCREATODUODENECTOMY 
Study Design 
RETROSPECTIVE ANALYSIS OF PROSPECTIVELY 
MAINTAINED DATABASE 
Study Participants 
PARTICIPANTS WHO HAVE UNDERGONE PANCREATIC 
RESECTIONS FROM APRIL  2016 TO MARCH 2020 
Planned Size of Sample (if 
applicable) 
Approximately  140 
Follow up duration (if applicable) 
90 DAYS 
Planned Study Period 
1 YEAR 
Research Question/Aim(s) 
 
To assess the usefulness and effectiveness of pre-
operative CPET in predicting morbidity and mortality 
after pancreatoduodenectomy 
 
 
 
 
 
FUNDING AND SUPPORT IN KIND 
FUNDER(S) 
(Names and contact details of ALL 
organisations providing funding and/or 
support in kind for this study) 
FINANCIAL AND NON FINANCIALSUPPORT 
GIVEN BY  
ROYAL BLACKBURN HOSPITAL, EAST 
LANCASHIRE HOSPITALS NHS TRUST 
HASLINGDEN ROAD, BLACKBURN, BB2 3HH 
CONTACT NUMBER: 01254 263555 
NON FINANCIAL SUPPORT 
 
ROLE OF STUDY SPONSOR AND FUNDER: 
Non-financial support for the study. 
 
 

STUDY FLOW CHART: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
STUDY PROTOCOL 
1 
BACKGROUND: 
Pancreatic resections, particularly Pancreatoduodenectomy, for tumors in the pancreas head, is 
considered the standard modality of management for pancreatic and periampullary tumors. The 
morbidity and mortality associated with the procedure, has improved in the recent times, but it 
still remains high. Post-operative pancreatic fistula, in particular, has an incidence ranging from 
20-25%1. The operability of the tumour not only depends on the initial staging of the tumour, but 
also on physiological status of the patient, fitness, pre-existing comorbidities and age. The use of 
cardiopulmonary Exercise Testing (CPET), in assessing physiological status of the patient has been 
in discussion, in the past two decades. The efficacy and use of CPET as a guide for pre-operative 
optimisation of the patient undergoing major abdominal surgeries, has been proven2. Levett D Z H 
et al. in 2017, provided Level 1 evidence, supporting the same and also drew guidelines for the 
clinicians for indications and interpretation of CPET for perioperative participants2.  
Chandrabalan V V et al. in 2013, conducted a retrospective study, which showed that CPET is 
useful to predict occurrence of post-operative pancreatic fistula, intra-abdominal abscess and 
post-operative length of hospital stay3. Junejo MA et al. in 2014, by a prospective study showed 
that, 
CPET 
can 
be 
used 
as 
an 
adjunct 
to 
predict 
post-operative 
outcomes 
in 
pancreatoduodenectomy. This study showed that raised VE/VCO2 in CPET could predict early post-
operative death4.  
Prospectively maintained database  
Retrospective analysis 
How many patients had a pre-operative CPET? 
Assess the usefulness of CPET values in predicting post-operative morbidity 
and mortality 
Morbidity in terms of: 
•
Pancreatic fistula 
•
Biliary fistula 
•
Delayed gastric emptying 
•
Bleeding 
•
Intra-abdominal 
collection 
•
Renal failure 
•
Cardiac complications 
•
Pulmonary complications 
•
Pulmonary embolism 
/DVT 
Mortality: 
•
In-hospital mortality 
•
30 days 
•
90 days 
Exclude – pancreatic resections 
other than pancreatoduodenectomy 

 
REFERENCES: 
1. 
Wu J.M., Kuo T.C., Chen H.A., et al. (2019). Randomized trial of oral versus enteral feeding for participants with 
postoperative pancreatic fistula after pancreatoduodenectomy. British Journal of Surgery,106,190–198. 
2. 
Levett D Z H, Jack S, Swart M et al. (2018). Perioperative cardiopulmonary exercise testing (CPET): consensus clinical 
guidelines on  indications, organization, conduct, and physiological interpretation. British Journal of 
Anaesthesia,120(3):484-500. 
3. 
Chandrabalan V V, McMillan D C, Carter R et al. (2013). Pre-operative cardiopulmonary exercise testing predicts 
adverse post-operative events and non-progression to adjuvant therapy after major pancreatic surgery. 
HPB,15:899-907. 
4. 
Junejo M A, Mason J M, Sheen A J et al. (2014). Cardiopulmonary exercise testing for preoperative risk assessment 
before pancreaticoduodenectomy for cancer. Annals of Surgical Oncology,21(6):1929-36. 
 
 
2 
RATIONALE: 
With the above mentioned background, we aim to do a retrospective analysis of participants who 
have undergone pancreatic resections, at our centre. The aim is to assess the ability of 
physiological parameters assessed by CPET, in predicting post-operative morbidity and mortality. 
This study also aims at evaluating and analysing a comparator group of participants who did not 
have CPET and assess their perioperative outcomes, in particular post-operative complications, 
with those who had CPET.  
 
3 
THEORETICAL FRAMEWORK 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4 RESEARCH QUESTION/AIM(S) 
Objectives: To assess if pre-operative cardiopulmonary exercise testing is useful and effective in 
predicting at risk participants for post-operative morbidity and mortality, who undergo Whipple’s 
surgery. 
Prospectively maintained database for 
pancreatic resections 
Retrospective review  
CPET done pre-operatively 
CPET not done pre-operatively 
CPET 
parameters 
Post-operative morbidity or 
mortality 
Post-operative morbidity or 
mortality 
Correlation 
Assess if P-Possum could predict 
the occurrence of post-operative 
complication and mortality 
Correlate CPET parameters and P-Possum’s 
ability to predict the occurrence of post-
operative complication 
Exclude – pancreatic resections 
other than pancreatoduodenectomy 

DATA ELEMENTS 
1. Participant flow 
 
Recruitment Details: 
Participants for the study will be identified from a prospectively maintained database, by database 
search from April 2016 to March 2020, online records, clinical portal and Somerset cancer registry. 
Duplicates will be removed, cases will be screened.  
This is a single centre study, to be done at, Royal Blackburn Hospital, East Lancashire Hospitals NHS 
trust, a District general Hospital in North of England. The study will be carried out in the department 
of General and HPB surgery, in liaise with Department of anaesthesia. This is the HPB referral centre 
for Lancashire and South Cumbria and incorporates participants referred for pancreatic surgery from 
three hospital trusts (Lancashire Teaching, University Hospital Morecambe Bay and Blackpool 
Teaching Hospitals). 
 
Arm/Group Information: 
The study will have two groups of participants, one who have undergone CPET pre-operatively and 
the other who have not undergone CPET. 
Group 1 – Participants who have undergone CPET as a part of pre-operative assessment as well as P-
POSSUM score calculation for predicting post-operative morbidity and mortality.  
P-POSSUM is a scoring system for general elective and emergency surgeries which takes into account 
various physiological and operative parameters to calculate risk of morbidity and mortality in terms 
of percentages. 
Group 2 – Participants who have not undergone CPET as a part of pre-operative assessment rather 
have only P-POSSUM calculated for predicting post-operative morbidity and mortality.  
 
Period of Overall Study: 
The study was conducted from February 2021 to March 2022. The database search was conducted 
and data collated. The study was conducted in one stage over a year. 
Participants:  
143 participants were recruited for the study during a period of 1 year. Out of 143 participants, 30 
participants had undergone CPET as a part of pre-operative assessment. 
 
2. Baseline Characteristics: 
 
Baseline Analysis Population Information: 
Data on baseline characteristics included age, sex, comorbidities, Rockwell frailty score, ASA grade, 
BMI. 

Data on study specific characteristics included dates of admission and discharge, diagnosis, details of 
surgery undergone, details of morbidity using Clavien-Dindo classification and mortality. Details of 
CPET and its measures as well as P-POSSUM scores were collated. 
CPET specific data collected:  
1) Exercise induced ST ischaemia- yes/no 
2) VO2 peak: actual and predicted 
3) Anaerobic threshold: 
4) VE/VCO2:  
5) Pulmonary function test- normal/ obstructive/ restrictive 
6) Duration of pedalling bike 
7) 30 day predicted risk 
 
 
3. Outcome Measures: 
 
Primary Outcome measures: 
Primary outcome was measured in terms of CPET/P-POSSUM predicted mortality compared to 
actual 30 day mortality. 
• 
In-hospital mortality 
• 
30 days 
• 
90 days 
 
Secondary outcome measures:  
Secondary outcome was measured in terms of CPET/ P-POSSUM predicted morbidity compared to 
actual morbidity (Clavien-Dindo grade 3 and above). 
Morbidity in terms of: 
• 
Post-operative pancreatic fistula 
• 
Biliary fistula 
• 
Delayed gastric emptying 
• 
Bleeding 
• 
Intra-abdominal collection 
• 
Renal failure 
• 
Cardiac complications 
• 
Pulmonary complications 
• 
Pulmonary embolism /DVT 
 
The occurrence of morbidity and mortality were measured in terms of numbers and percentages. 
The calculated risk of morbidity and mortality by CPET and P-POSSUM are in terms of percentages, 
ranging from 0 to 100%, higher the percentage leading to worse outcome. 
 
Statistical analyses overview:  
The baseline characteristics were analysed using percentages and frequencies (mean, median, 
mode, standard deviation). Chi-square test was used to assess if the two study groups were 

comparable. The p-value calculated was considered significant if <0.05 and confidence interval of 
95%. 
The study specific measures were analysed using parametric and non-parametric tests and binary 
logistic regression analyses to compare predicted to actual mortality and morbidity, between the 
participants who have had CPET and those who have not. 
Univariate and multivariate analysis were done to assess if CPET measures could be used to predict 
occurrence of post-operative complications and morbidity. 
 
4. Adverse Event information: 
This was a retrospective review of a prospectively maintained database. 
No adverse events were overcome during the time of the study 
 
5. Limitations and Caveat: 
This was a retrospective review of a prospectively maintained database. The participants who 
underwent CPET was small compared to participants who did not. A prospective study with a large 
sample size is required to obtain more reliable results. 
 
6. Certain Agreements: 
All PIs are employees of Sponsor. 
There is no specified results disclosure agreement between the PIs and sponsor. 
 
7. Results Point of Contact 
Name: Miss Meghana Taggarsi (Principal Investigator) 
Organization Name: East Lancashire Hospitals NHS Trust 
Phone: 07471565288 
Email Id: meghana.t87@gmail.com 
 
8. Results of the study 
143 participants had Pancreatoduodenectomy during the study period. CPET was performed in 30 
participants (21%). The participants’ age was 67 ±9 (Mean±SD). Forty participants (28.2%) had 
developed intra-abdominal collection (Clavien-Dindo III). In the CPET subgroup, Anaerobic Threshold 
(AT) ≤ 14 on CPET was a risk factor to develop intra-abdominal collection, according to univariate 
analysis (60% Vs 9%, p-value 0.02) and multivariate analysis (HR 3.5, 95% CI 1.6-657, p-value 0.02). 
Another significant risk factor was post-operative pancreatic leak (POPF) (40% Vs 22%, p-value 0.04). 
By this study we concluded that participants who have Anaerobic Threshold ≤ 14 on CPET, are more 
likely to develop intra-abdominal collection requiring drainage after Pancreatoduodenectomy.  This 
group of participants will be less likely to start chemotherapy early.