Computed Tomography Coronary Angiography (CTCA) Prior to Chronic Total Occlusion (CTO) Percutaneous Coronary Intervention (PCI) - a Feasibility Study
Phase: NA
Conditions: Chronic Total Occlusion of Coronary Artery
Sponsor: Sandwell & West Birmingham Hospitals NHS Trust

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Computed Tomography Coronary Angiography (CTCA) prior to Chronic Total Occlusion (CTO) 
Percutaneous Coronary Intervention (PCI) - a feasibility study 
 
TRIAL SUMMARY 
Trial Title 
Computed Tomography Coronary Angiography (CTCA) 
prior to Chronic Total Occlusion (CTO) Percutaneous 
Coronary Intervention (PCI) - a feasibility study 
Summary of Trial design 
Randomised, prospective, single centre feasibility study of 
CTCA prior to CTO PCI 
Site and Chief Investigator 
Sandwell and West Birmingham NHS Trust, Birmingham, 
United Kingdom 
Vinoda Sharma 
Participant population 
Patients undergoing CTO PCI 
Planned sample size 
20 
Number of sites 
1  
Intervention duration 
Prior to index CTO PCI procedure 
Follow up duration 
6 months 
Planned trial duration 
1 year 
Primary objective 
To determine if CTCA prior to CTO PCI results in improved 
procedural success rate? 
Secondary objectives 
i) To determine if CTCA prior to CTO PCI results in improved 
angina as determined by Seattle Angina Questionnaire 
(SAQ)? 
ii) To determine if CTCA prior to CTO PCI reduces the need 
for a second procedure due to improved procedural success 
rate? 
 iii) Are there procedural differences between the 
intervention arm (CTCA) and usual care  
Intervention 
Randomised to CTCA versus no CTCA prior to CTO PCI 
 
 
 
 
 
 
 
 
 
 

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ABBREVIATIONS: 
 
CABG: Coronary Artery Bypass Graft  
 
CAD: Coronary Artery Disease 
 
CTCA: Computed Tomography Coronary Angiogram 
 
CTO: Chronic Total Occlusion 
 
J-CTO: Japanese Chronic Total Occlusion 
 
PCI: Percutaneous Coronary Intervention 
 
QALYS: Quality Adjusted Life Years 
 
QoL: Quality of Life 
 
SAQ: Seattle Angina Questionnaire 
 
 

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Trial Protocol Synopsis 
Item 
Description 
 
Title 
Computed Tomography Coronary Angiography (CTCA) prior 
to Chronic Total Occlusion (CTO) Percutaneous Coronary 
Intervention (PCI)  
 
Introduction 
Description of research question 
Null Hypothesis: 
CTCA performed prior to CTO PCI will not improve 
procedural success  
 
Existing knowledge: 
A chronic total occlusion (CTO) is present in 15-20% of 
patients with angina who are referred for coronary 
angiography. Due to the complexity of occlusive coronary 
artery disease (CAD), including a high prevalence of calcium 
and tortuosity within long segments of disease, CTO PCI is 
associated with higher procedural complication rates (11). 
Inability to detect the intraluminal path in the CTO artery, 
combined with calcification and tortuosity can result in 
unsuccessful guidewire crossing and procedural failure.  
Successful CTO PCI has been shown to improve Quality of 
Life (QoL) at 12 months(4). These patients are more likely to 
be angina free at 12 months (5, 6) as assessed by the 
Seattle Angina Questionnaire (SAQ) (7, 8). CTO PCI in 
symptomatic patients is cost effective and results in greater 
quality-adjusted-life-years (QALYS)(9, 10). 
 
CTO percutaneous coronary intervention (PCI) procedure 
success rates increased from 68% to 79% between 2000 
and 2011, and are as high as 90% when performed by high-
volume CTO operators (2, 3).   Complexity of the CTO is 
determined by several factors and several CTO complexity 
scores, derived from (invasive) angiographic lesion and 
clinical characteristics, have been shown to correlate with 
procedural success and complication rates (JCTO(12), 
PROGRESS(13), RECHARGE(14), Euro-CASTLE(15)).  
The most commonly utilised score is the J-CTO 
(Multicenter Chronic Total Occlusion Registry of Japan)(12) 
which assigns a score of 1 each to the angiographic CTO 
proximal cap (tapered or blunt), calcification, tortuosity 
(>450), lesion length (≥20mm) and previous failure, with a 
maximum score =5. Scores ≥2 are considered CTOs that are 
difficult to perform and require advanced techniques for 
successful revascularisation.  
In a proportion of these patients, the first procedure either 
fails completely or partially succeeds in forming a tract 
within the occluded artery but this is inadequate for stent 
delivery and the patient requires a second procedure, 
occasionally a third for complete success and 

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reconstruction of the fully occluded artery. 
 
Angiographically, the CTO artery usually shows a short 
proximal portion of dye filled artery prior to the occlusion. 
In most patients there are some collaterals from the 
contralateral coronary artery which try to fill part of the 
occluded CTO artery. However the actual body of the CTO is 
not visible angiographically. 
Computed Tomography Coronary Angiography (CTCA) can 
delineate the coronary anatomy in 3-dimensions, 
determining atherosclerotic plaque and occlusion location, 
severity and morphology.  This makes it an attractive 
modality to assess the coronary CTO. Development of a 
CTCA based complexity score for stratifying CTOs by 
difficulty resulted in the CT-RECTOR score (Computed 
Tomography Registry of Chronic Total 
Occlusion Revascularization, table 1)(16). Variables included 
in this score are multiple occlusions, blunt stump, severe 
calcification, bending, duration of CTO ≥12 months and 
previously failed PCI (all scored 1). The CT-RECTOR score 
correlates with the  J-CTO score and has a better area under 
ROC curve (ROC AUC 0.83 for CT-RECTOR  score and  0.71 
for J-CTO, p < 0.001) and predicts CTO PCI success (16) 
 
The role of routine CTCA pre-CTO PCI is as yet undefined as 
current practice involves the use of CTCA in patients who 
have had an unsuccessful CTO PCI attempt or previous 
coronary artery bypass grafting (CABG).  
 
 
Need for a feasibility study:  
 
Current practice at our centre involves the use of CTCA in 
patients who have had an unsuccessful CTO PCI attempt or 
previous coronary artery bypass grafting (CABG) but the 
role of routine CTCA pre-CTO PCI is as yet undefined.  
 
The small additional investment of a CTCA could help 
plan/improve a complex procedure and may reduce the 
need for additional procedures and readmissions.  
 
The mean acute treatment cost of a CTO PCI is 
approximately (combined day-case –ordinary elective spell) 
£6933 (9, 17) whereas the approximate cost of a CTCA is 
£360 (as per local billing). Elective readmission for a failed 
CTO PCI procedure would entail an additional financial (to 
the provider) and emotional cost (to the patient).  
 
The cost of an additional CTO PCI procedure aside,  
readmission and bed charges themselves can reach 
£1000/day (readmission =£255/day)(17)and bed 

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cost=£600/day). Including the cost of a second CTO PCI 
procedure (combined day-case –ordinary elective spell) 
£6933 (9, 17), the overall cost can total to £10,000. In 
contrast, the cost of a CTCA is £360 (as per local billing). 
Financial costs are one part of the issue, but a second CTO 
PCI procedure can also heighten patient anxiety and 
discomfort which are well known in patients prior to any 
PCI. 
 
A feasibility study will help establish the role of a CTCA prior 
to CTO PCI to positively influence strategy and/or 
outcomes. 
 
Objectives 
Primary:   
i) 
Does performing a CTCA prior to CTO PCI 
improve the success of the CTO procedure? 
Secondary:  
i)      
To determine if CTCA prior to CTO PCI results in 
improved angina as determined using the 
Seattle Angina Questionnaire (SAQ) by SAQ. 
ii) 
To determine if CTCA prior to CTO PCI reduces 
the need for a second procedure (due to 
improved procedural success rate). 
iii) 
To assess if there are procedural differences 
between the intervention arm (CTCA) and usual 
care arm 
Comparators 
CTCA versus no CTCA prior to CTO PCI 
 
Trial design 
Randomised (1:1), prospective, single centre study 
 
Methods (see figure 1) 
Study setting 
Sandwell and West Birmingham NHS Trust, Birmingham, 
United Kingdom 
 
Eligibility Criteria 
Inclusion Criteria: 
Patients meeting all the below criteria will be included 
 
≥18 years 
 
CTO with J-CTO score≥2 
 
Appropriate indication for CTO PCI 
 
Adequate CTCA images for analysis 
 
Exclusion criteria: 
Patients meeting any of the following criteria will be 
excluded 
 
<18 years of age 
 
CTO with J-CTO score<2 
 
Inadequate/degraded CTCA images 
 
Pregnant/lactating women 
 
Patients with severe contrast allergy 
 
Patients unable to provide written informed 
consent 

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Intervention 
Experimental group: CTCA prior to CTO PCI 
Conventional group: CTO PCI 
 
Patients will be randomised to CTCA or no CTCA prior to 
CTO PCI (figure 1) 
Outcomes 
Outcomes 
 
Primary endpoint  
i. 
CTO PCI success rate in CTCA arm versus no 
CTCA arm  
 
Secondary endpoints 
i. 
Angina by the SAQ summary score at 6 months 
ii. 
Compare the number of patients who required 
a second CTO PCI procedure in the CTCA arm 
versus no CTCA arm 
iii. 
Procedural differences between the 
intervention CTCA arm versus no CTCA arm 
including: 
a) Health Economics: 
 
Cost saved per patient due to improved 
success and reduction in readmission or 
further  procedure 
b) CTO PCI efficiency: 
 
Wire crossing time 
 
Procedure time 
c) CTO PCI safety outcomes:  
 
Procedural complications (Ellis perforation, 
tamponade, acute kidney injury/contrast 
induced nephropathy, access site bleeding, 
donor vessel injury) 
 
Radiation: CTCA dose, CTO PCI dose, and 
combined CTCA and CTO PCI dose 
 
Contrast: CTCA volume, CTO PCI volume, 
and combined CTCA and CTO PCI volume 
d) Change in CTO PCI strategy hierarchy as   
a result of the CTCA review  
 
Participant/project timeline 
Please see figure 2 
 
Sample size 
This is a feasibility study- to ensure completion within a 
year, we have estimated 20 patients, randomised 1:1 to 
each arm (10 patients per arm) as a sample size in a 
moderate size hospital which performs approximately 100 
CTO PCIs annually  
 
Intervention assignment 
Block randomisation with sealed envelope technique 
 
Data collection, management and 
analysis 
 
eCRF and online database to collect demographic, 
procedural and SAQ information 

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 
SAQ summary score at 6 months post PCI 
 
Blood samples pre and post PCI 
 
Comparison of demographics, procedural details, 
procedural success and complications, bloods, SAQ, 
and financial cost between the CTCA and non-CTCA 
groups 
 
Categorical variables will be presented as 
percentage and compared with the chi square or 
Fisher’s test 
 
Continuous variables will be presented as median 
(range) and compared with student’s t-test or 
Mann Whitney test. 
 
In addition, modelling will be performed by binary 
logistic regression analysis to predictors of CTO PCI 
success.  
 
Monitoring 
CTO PCI procedural adverse events will be reported as usual 
on the national database and this data will be collected in 
the eCRF. 
 
Ethics 
Ethical approval for this prospective study will be obtained 
All patients will be consented prior to inclusion in this study 
 
Blood 
Routine blood tests will be performed immediately before 
the CTO PCI and after the procedure prior to discharge as 
standard of care 
 

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Figure 1: Patient flow pathway 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Symptomatic CTO patients                           
n=20 
1:1 randomisation to  CTCA 
CTCA prior to CTO PCI 
CTO PCI 
No CTCA  
CTO PCI 
SAQ  initial 
in all patients 
SAQ  final 6 months 
 post-procedure 
in all patients 
Routine blood tests              
pre and post procedure 

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Figure 2: Participant/project Timeline 
 
Initial 2 months        Next 4months                              Next 4months                                      Next 2months 
 
 
 
 
                        
 
 
 
 
 
 
 
 
      
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Set up  
Patient identification and inclusion 
Randomisation to CTCA (yes/no)CTO PCI 
 
Patient follow up (telephonic) 
SAQ summary score 
 
Data collection and 
analysis 
Health economic analysis 
and Summary report 

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References: 
 
1. 
Opolski MP, Achenbach S. CT Angiography for Revascularization of CTO: Crossing the Borders 
of Diagnosis and Treatment. JACC Cardiovasc Imaging. 2015;8(7):846-58. 
2. 
Patel VG, Brayton KM, Tamayo A, Mogabgab O, Michael TT, Lo N, et al. Angiographic success 
and procedural complications in patients undergoing percutaneous coronary chronic total occlusion 
interventions: a weighted meta-analysis of 18,061 patients from 65 studies. JACCCardiovascular 
interventions. 2013;6(2):128-36. 
3. 
Sharma V, Jadhav ST, Harcombe AA, Kelly PA, Mozid A, Bagnall A, et al. Impact of proctoring 
on success rates for percutaneous revascularisation of coronary chronic total occlusions. Open 
Heart. 2015;2(1):e000228. 
4. 
Simon W. The Consistent CTO Study. 2018. 
5. 
Olivari Z, Rubartelli P, Piscione F, Ettori F, Fontanelli A, Salemme L, et al. Immediate results 
and one-year clinical outcome after percutaneous coronary interventions in chronic total occlusions: 
data from a multicenter, prospective, observational study (TOAST-GISE). J Am Coll Cardiol. 
2003;41(10):1672-8. 
6. 
Werner GS, Martin-Yuste V, Hildick-Smith D, Boudou N, Sianos G, Gelev V, et al. A 
randomized multicentre trial to compare revascularization with optimal medical therapy for the 
treatment of chronic total coronary occlusions. Eur Heart J. 2018;39(26):2484-93. 
7. 
Chan PS, Jones PG, Arnold SA, Spertus JA. Development and validation of a short version of 
the Seattle angina questionnaire. Circ Cardiovasc Qual Outcomes. 2014;7(5):640-7. 
8. 
Spertus JA, Winder JA, Dewhurst TA, Deyo RA, Prodzinski J, McDonell M, et al. Development 
and evaluation of the Seattle Angina Questionnaire: a new functional status measure for coronary 
artery disease. J Am Coll Cardiol. 1995;25(2):333-41. 
9. 
Gada H, Whitlow PL, Marwick TH. Establishing the cost-effectiveness of percutaneous 
coronary intervention for chronic total occlusion in stable angina: a decision-analytic model. Heart. 
2012;98(24):1790-7. 
10. 
Grantham JA, Jones PG, Cannon L, Spertus JA. Quantifying the early health status benefits of 
successful chronic total occlusion recanalization: Results from the FlowCardia's Approach to Chronic 
Total Occlusion Recanalization (FACTOR) Trial. Circ Cardiovasc Qual Outcomes. 2010;3(3):284-90. 
11. 
Tajti P, Brilakis ES. Chronic Total Occlusion Percutaneous Coronary Intervention: Evidence 
and Controversies. J Am Heart Assoc. 2018;7(2). 
12. 
Morino Y, Abe M, Morimoto T, Kimura T, Hayashi Y, Muramatsu T, et al. Predicting 
successful guidewire crossing through chronic total occlusion of native coronary lesions within 30 
minutes: the J-CTO (Multicenter CTO Registry in Japan) score as a difficulty grading and time 
assessment tool. JACCCardiovascular interventions. 2011;4(2):213-21. 
13. 
Christopoulos G, Kandzari DE, Yeh RW, Jaffer FA, Karmpaliotis D, Wyman MR, et al. 
Development and Validation of a Novel Scoring System for Predicting Technical Success of Chronic 
Total Occlusion Percutaneous Coronary Interventions: The PROGRESS CTO (Prospective Global 
Registry for the Study of Chronic Total Occlusion Intervention) Score. JACC Cardiovasc Interv. 
2016;9(1):1-9. 
14. 
Maeremans J, Spratt JC, Knaapen P, Walsh S, Agostoni P, Wilson W, et al. Towards a 
contemporary, comprehensive scoring system for determining technical outcomes of hybrid 
percutaneous chronic total occlusion treatment: The RECHARGE score. Catheter Cardiovasc Interv. 
2018;91(2):192-202. 
15. 
Szijgyarto Z, Rampat R, Werner GS, Ho C, Reifart N, Lefevre T, et al. Derivation and Validation 
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16. 
Opolski MP, Achenbach S, Schuhbäck A, Rolf A, Möllmann H, Nef H, et al. Coronary 
computed tomographic prediction rule for time-efficient guidewire crossing through chronic total 
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Improvement N. 2019/20 National Tariff Payment System. 2019. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Appendix 
Costing (approximate):  
Grade of staff/Test 
required 
 Role 
Cost per 
patient 
Work Time 
Equivalent  
Period of 
time 
Total Cost all 
patients  
CTCA per patient 
- 
£360/- 
- 
- 
£7200 
Blood tests per 
patient 
- 
£30 per set x2 
lots=£60 
 
- 
£1200 
Clinical 
fellow/registrar 
Patient consent, 
review of blood 
tests, telephone 
follow up 
- 
 
 
£16,300 
Total 
 
 
 
 
£24,700