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Eur Heart J Open
Eur Heart J Open
ehjopen
European Heart Journal Open
2752-4191
Oxford University Press US

38025651
10.1093/ehjopen/oead111
oead111
Protocol Paper
Interventional Cardiology and Cardiac Surgery
AcademicSubjects/MED00200
Safety and care of no fasting prior to catheterization laboratory procedures: a non-inferiority randomized control trial protocol (SCOFF trial)
https://orcid.org/0000-0003-3142-4503
Ferreira David Department of Cardiovascular Medicine, John Hunter Hospital, Lookout Road, Newcastle 2305, Australia
School of Medicine and Public Health, University of Newcastle, University Drive, Newcastle 2308, Australia
Hunter Medical Research Institute, Kookaburra Circuit, Newcastle 2305, Australia

Hardy Jack Department of Cardiovascular Medicine, John Hunter Hospital, Lookout Road, Newcastle 2305, Australia

Meere Will Department of Cardiology, Gosford Hospital, 75 Holden Street, Gosford 2250, Australia

Butel-Simoes Lloyd Department of Cardiovascular Medicine, John Hunter Hospital, Lookout Road, Newcastle 2305, Australia

McGee Michael Department of Medicine, Tamworth Rural Referral Hospital, Dean Street, Tamworth 2340, Australia

Whitehead Nicholas Department of Cardiology, Calvary Mater Hospital, 20 Edith Street, Newcastle 2298, Australia

Healey Paul Department of Anaesthesia, John Hunter Hospital, Lookout Road, Newcastle 2305, Australia

Ford Tom Department of Medicine, Tamworth Rural Referral Hospital, Dean Street, Tamworth 2340, Australia

Oldmeadow Christopher Hunter Medical Research Institute, Kookaburra Circuit, Newcastle 2305, Australia

https://orcid.org/0000-0001-9800-1308
Attia John School of Medicine and Public Health, University of Newcastle, University Drive, Newcastle 2308, Australia
Hunter Medical Research Institute, Kookaburra Circuit, Newcastle 2305, Australia

Wilsmore Bradley Department of Cardiovascular Medicine, John Hunter Hospital, Lookout Road, Newcastle 2305, Australia
School of Medicine and Public Health, University of Newcastle, University Drive, Newcastle 2308, Australia

Collins Nicholas Department of Cardiovascular Medicine, John Hunter Hospital, Lookout Road, Newcastle 2305, Australia
School of Medicine and Public Health, University of Newcastle, University Drive, Newcastle 2308, Australia
Hunter Medical Research Institute, Kookaburra Circuit, Newcastle 2305, Australia

Boyle Andrew Department of Cardiovascular Medicine, John Hunter Hospital, Lookout Road, Newcastle 2305, Australia
School of Medicine and Public Health, University of Newcastle, University Drive, Newcastle 2308, Australia
Hunter Medical Research Institute, Kookaburra Circuit, Newcastle 2305, Australia

De Rosa Salvatore Handling Editor
Corresponding author. Tel: +61 02 4921 4200, Email: david.ferreira@health.nsw.gov.au
Conflict of interest: None declared.

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© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.
2023
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

Abstract

Aims

Cardiac catheterization procedures are typically performed with local anaesthetic and proceduralist guided sedation. Various fasting regimens are routinely implemented prior to these procedures, noting the absence of prospective evidence, aiming to reduce aspiration risk. However, there are additional risks from fasting including patient discomfort, intravascular volume depletion, stimulus for neuro-cardiogenic syncope, glycaemic outcomes, and unnecessary fasting for delayed/cancelled procedures.

Methods and results

This is an investigator-initiated, multicentre, randomized trial with a prospective, open-label, blinded endpoint (PROBE) assessment based in New South Wales, Australia. Patients will be randomized 1:1 to fasting (6 h solid food and 2 h clear liquids) or to no fasting requirements. The primary outcome will be a composite of hypotension, hyperglycaemia, hypoglycaemia, and aspiration pneumonia. Secondary outcomes will include patient satisfaction, contrast-induced nephropathy, new intensive care admission, new non-invasive or invasive ventilation requirement post procedure, and 30-day mortality and readmission.

Conclusions

This is a pragmatic and clinically relevant randomised trial designed to compare fasting verse no fasting prior to cardiac catheterisation procedures. Routine fasting may not reduce peri-procedural adverse events in this setting.

Fasting
Preoperative care
Angiography
Cardiovascular surgical procedures
Patient satisfaction
John Hunter Hospital Charitable Trust
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pmcIntroduction

Cardiac catheterization procedures are typically performed with local anaesthetic and proceduralist guided sedation. Fasting (4–6 h for solid food and 2 h for clear liquids) is routinely recommended prior.1 Fasting is implemented to reduce risk of aspiration, a rare but significant clinical event. A meta-analysis of randomized trials demonstrated that longer fasting (>4 h) is not associated with differences in gastric volumes and pH compared with shorter fasting (2–4 h)2; in fact, the analysis showed that shorter fasting periods seemed to have lower rates of aspiration with reduced thirst and hunger.

Evidence to support fasting for cardiac catheterization procedures is lacking.3,4 An observational study showed that in practice, patients fast significantly longer than recommended.5 In over 1000 patients, the average fasting period was 11.6 h with high rates of hunger (47%) and headache (11.7%), similar to the anecdotal experience at our institutions. Longer fasting periods may increase the likelihood of patient discomfort, post-procedure nephropathy, hypotension, and adverse glycaemic outcomes.

There are numerous potential benefits to removing fasting requirements including improved patient satisfaction, superior hydration status, and prevention of procedure delays and cancellations. CHOW NOW, published in abstract form, compared fasting and no-fasting before cardiac catheterization procedures.6 This single-centre randomized trial suggested non-inferiority of no fasting with a primary composite endpoint of contrast-induced nephropathy, periprocedural hypotension, aspiration pneumonia, nausea and vomiting, hyperglycaemia, and hypoglycaemia. CHOW NOW accepted an absolute risk increase of 5.9% in the no-fasting arm as the upper limit of the non-inferiority margin. The aim of our study is to assess non-inferiority of no-fasting compared with fasting for cardiac catheterization (including coronary angiography and planned percutaneous coronary intervention) and cardiac device-related procedures.

Methods

Clinical trial design

This is a multicentre non-inferiority randomized trial with a prospective open-label, blinded endpoint design (PROBE). Inclusion and exclusion criteria are listed in Table 1. Coronary angiography, percutaneous coronary intervention, device implantation/replacement and lead revisions will be included. Structural cardiac interventions, calcium modification therapy, biventricular cardiac resynchronization therapy and electrophysiology procedures will be excluded. The composite primary endpoints and secondary outcomes are listed in Table 2. Thirty-day outcomes will be assessed via International Classification of Diseases 10th Revision diagnoses on discharge summaries. Patients will be randomized 1:1 via REDCAP to fasting (minimum of 6 h solid food and 2 h clear liquids) or to no-fasting requirement. Those in the no-fasting arm will be encouraged to have their regular meals but will not be mandated to do so. Time between solid food and clear liquid intake and procedure start will be collected. Procedure start will be defined as time of local anaesthesia administration. Single-sequence randomization will be performed with stratification by procedure type (coronary-based procedure vs. device implantation) and procedure site. Proceduralists will be permitted to know group allocation. Patient satisfaction will be assessed with the prospectively validated preoperative fasting questionnaire by Popovic et al. (Table 3).11 Data collection will occur on REDCAP, a secure and internationally recognized database. The clinical trial flow diagram can be found in Figure 1.

Figure 1 Clinical trial flow diagram.

Table 1 Inclusion and exclusion criteria

Inclusion criteria	
Aged over 18 years of age

Referred for catheterization laboratory procedures

Coronary angiography

Percutaneous coronary intervention

Device implantation or replacement (pacemakers and defibrillators)

Device lead revision (pacemakers and defibrillators)

	
Exclusion criteria	
Inability to provide informed consent

Pregnant or breastfeeding females

Requirement for a general anaesthetic

Emergent intervention (e.g. ST-elevation myocardial infarction for laboratory activation)

Planned complex catheterization laboratory interventions

Calcium modification therapy—Rotational atherectomy, shockwave lithotripsy

Mechanical circulatory support—Impella or intra-aortic balloon pump

Structural interventions—aortic and mitral valve interventions

Electrophysiologic studies—diagnostic and/or ablation

Biventricular pacing with cardiac resynchronization therapy

	

Table 2 Primary and secondary outcome components and definitions

Primary outcomes	
Aspiration pneumonia (diagnosis made on clinical and radiographic criteria)

Syndrome of hypoxia/tachypnoea/tachycardia/fever with X-ray changes after an aspiration event7

Periprocedural hypotension

<90 mmHg systolic or low blood pressure requiring intervention (e.g. medications or fluid bolus)

Hypoglycaemia—blood sugar level <3.9 mmol/L8

Hyperglycaemia—blood sugar level >11 mmol/L9

	
Secondary outcomes	
Contrast-induced nephropathy

25% increase in serum creatinine from baseline or a 0.5 mg/dL (44 µmol/L) increase in absolute serum creatinine value 48–72 h after intravenous contrast administration10

New intensive care unit admission required post procedure

New non-invasive ventilation or intubation requirement post procedure

30-day readmission

30-day mortality

Patient reported outcomes of satisfaction and comfort11

Pre-procedure EQ-5D quality of life score

	

Table 3 Patient satisfaction questionnaire

Patient satisfaction questionnaire (5-point ordinal scale response)	
Pre-procedure questions11I am thirsty

I am hungry

My voice is hoarse

I am feeling anxious

I feel weak

I am nauseous

	Response optionsStrongly agree

Agree

Neutral

Disagree

Strongly disagree

	

Periprocedural instructions and care

Sodium-glucose transport protein 2 (SGLT2) inhibitors and metformin will be withheld for 24 h before and after the procedure for all patients, regardless of fasting status. If on insulin therapy, those who are not required to fast will be instructed to have their normal insulin dose based on food intake. Intravenous fluid hydration for angiography will be dictated by the proceduralist; however, the POSEIDON protocol will be suggested for those with glomerular filtration rates below 45 mL/min/m2 without evidence of fluid overload.12 Sedation will be at the discretion of the physician and normally includes fentanyl ± midazolam titrated to effect. Sedation type and doses will be recorded.

Ethics and trial registration

Ethics approval is confirmed via the Hunter New England Research Ethics Committee. Ethics reference number: 2021/PID02660. The trial has been registered on the Australia New Zealand Clinical Trials Registry (ACTRN12622001455752). Recruitment is ongoing across six sites in New South Wales, Australia: John Hunter Hospital, Calvary Mater Hospital, The Maitland Hospital, Belmont District Hospital, Gosford Hospital and Tamworth Rural Referral Hospital.

Sample size calculation

Based on the data from CHOW NOW, our stipulated composite primary outcome occurred in 5.9% of the fasting arm compared with 5.1% in the non-fasting arm. We assume that the 95% probability distribution in the primary outcome is between 3 and 12%, the number of participants with outcomes in each group follows a binomial distribution, and the proportion of patients experiencing outcomes follows a beta distribution. Through simulations, we estimate 300 patients per arm are required to declare non-inferiority on 80% of simulations (power) and incorrectly declare non-inferiority when the true difference is 3% larger in the non-fasting group (i.e. upper limit of the non-inferiority margin is an increase of 3% in the composite endpoint compared with fasting group) on 5% of simulations (a Type 1 error rate of 5%). We aim to recruit 600 patients in the coronary intervention arm and 100 patients in the device arm, making a total sample size of 700.

Statistical analysis

Endpoints will be assessed by a blinded clinical events committee of three physicians: an electrophysiologist, interventional cardiologist, and cardiac anaesthetist. Continuous variables will be reported as means ± standard deviation or as medians and interquartile ranges, if appropriate. Categorical variables will be stated as absolute and relative frequencies and compared using the χ2 test. The coronary angiography and device-related procedures will be analysed within a single cohort. The posterior distribution for the between-group difference in the proportion of patients experiencing the composite outcome will be estimated within a Bayesian framework. The posterior probability that the difference in proportion is no more than the non-inferiority margin of 3% will be estimated from this posterior distribution. The non-fasting treatment will be declared non-inferior to the fasting treatment, if this probability exceeds 95%. A 95% credible interval for the difference will be presented for the primary outcome and estimated for the dichotomous secondary outcomes. Ninety-five per cent posterior intervals for the difference in means will be presented for the continuous outcomes estimated using the No-UTURN sampler and a combination of non-informative and informative prior distributions. Participants with any missing data will have values drawn from their assumed distributions within the Bayesian model. The analysis will have the intention to treat multiple imputation the primary method of dealing with missing outcome data, imputing missing variables using the chained regression equations method. Pre-specified post hoc analyses will include coronary vs. device-related procedures, diagnostic vs. interventional coronary artery procedures, inpatient vs. outpatient procedures, sedation provision, body mass index, and age.

Discussion

There is no prospective randomized data supporting fasting prior to cardiac catheterization laboratory procedures. While there are theoretical benefits to fasting, there are also risks. The CHOW NOW study was of great interest to the cardiology community but has not yet been published in a peer-reviewed journal.1,6 We suggest that finding non-inferiority of no fasting would be practice changing. This is based on the preceding evidence from CHOW NOW, retrospective reviews, and the clinical experience of interventional cardiologists: aspiration is extremely rare during emergent procedural intervention. Indeed, those undergoing emergency interventions would probably have greater risk of aspiration than those having non-emergent procedures. Given aspiration events are so rare, a clinical trial powered purely to look for differences in aspiration rates would require unfeasibly large patient numbers. We have powered the analysis to accept a 3% absolute risk increase in the primary composite outcome (around a 50% relative risk increase) within the no-fasting arm. The authors suggest that this risk increase in the composite primary endpoint of hypotension, hyperglycaemia, hypoglycaemia, and aspiration in the no-fasting group would be clinically acceptable, provided aspiration rates were not significantly higher in the intervention arm.

Removing fasting requirements may benefit hospital and healthcare systems. Reducing delays in procedures will allow for improved cardiac catheterization laboratory efficiency by improving patient flow, decreasing length of stay and healthcare expenditure.

The inclusion of device-related procedures is novel to this study. At our centres, device interventions are performed in a similar manner to coronary angiography, with local anaesthetic and proceduralist guided sedation. As with coronary procedures, there is a paucity of data to support the role of fasting prior to device implantation. There is no reason to expect that outcomes would be different based on procedure type; rather, the risk of aspiration would more likely be influenced by individual patient characteristics.

In the spirit of integrity and openness, de-identified patient-level data will be available to researchers who provide sound analysis proposals. Our pre-specified primary outcomes match outcomes assessed by the CHOW NOW investigators. There may be a role for combining individual patient-level data from CHOW NOW and other fasting trials to improve precision in the results.

Conclusion

After completion, this will be the largest randomized trial in the pre-procedural fasting space. Routine fasting prior to cardiac laboratory procedures may not reduce the risk of periprocedural outcomes. We are performing a clinically relevant, pragmatic, randomized multicentre trial to assess this question in a prospective fashion. The authors argue that if the non-inferiority of no-fasting is confirmed, it would be a practice-changing finding. This may also have implications for fasting requirements for other non-cardiac procedures that utilize conscious sedation.

Lead author biography

David Ferreira is a Cardiology Trainee and PhD candidate at the Cardiovascular Department, John Hunter Hospital, Newcastle, Australia. He obtained his medical degree from the University of New England and completed his Physician’s Training at Liverpool Hospital in Sydney. His research focused on randomized trials of low-cost interventions to improve patient care.

Data availability

De-identified patient level data will be available to researchers who provide sound analysis proposals.

Funding

Statistical analysis is supported by a grant from the John Hunter Hospital Charitable Trust.
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