Feasibility Study of Early Review and Early Cardiac Rehabilitation After Coronary Artery Bypass
Condition: Coronary Artery Disease; Quality of Life
MeSH terms: Coronary Artery Disease
Study type: Interventional

Summary: 
      Current care after coronary artery bypass grafting (CABG) involves a check-up 6 weeks after
      hospital discharge followed by an exercise programme called cardiac rehabilitation (CR) from
      8 weeks. This practice is not evidence-based; it is therefore uncertain if earlier check-up
      and CR would promote quicker recovery. The proposed research will examine the feasibility of
      having check-up at 3 weeks and CR from 4 weeks after hospital discharge, and the associated
      advantages.

      The investigators plan to recruit 100 patients undergoing planned CABG through a median
      sternotomy, at 2 NHS hospitals over 5 months. They will include 18 to 75 year olds, capable
      of giving Informed consent and fit for CR exercises.

      Patients will be approached before surgery and given study information to read. Four days
      after surgery, patients who are willing to take part will have their routine clinical
      examination, blood tests, chest x-rays and heart tracings reviewed to determine suitability
      for the study. The investigators will obtain informed consent, do breathing tests and, ask
      the patients to complete a general health questionnaire. A computer will allocate patients
      equally to the proposed care (intervention group) or current care (control group). After
      discharge, patients will attend check-up and semi-structured interview at 3 weeks
      (intervention group) or 6 weeks (control group) before starting CR from 4 weeks (intervention
      group) or 8 weeks (control group). CR will involve exercise classes once or twice a week for
      8 weeks, and fitness tests. Patients will have a final assessment at 26 weeks, with clinical
      examination, fitness and breathing tests, and completion of general health questionnaire.

      The investigators will analyse patients' and staff experiences, patient fitness levels,
      quality of life and costs, associated with each pathway. They will report potential benefits
      of proposed care, if any. This study findings will be used to design a larger trial to
      determine the best practice.
    

Detailed description: 
      Rationale and Background

      Currently following CABG, patients attend their first outpatient review six weeks after
      hospital discharge, where recovery is assessed and fitness to commence CR is determined. CR
      is then started from eight weeks. In a survey conducted in May/June 2017 by the
      investigators, 35 of 42 UK cardiac centres responded, and confirmed this as current practice.
      The long interval before postoperative review and CR extends the period of vulnerability and
      inactivity for patients, with patients often seeking medical attention for surgery-related
      complications during this period. In a prospective observational study (FORCAST6), the
      investigators found that 44% of patients sought further medical help during this 6 week
      period, and 41% would like an earlier review. This feasibility study will examine the
      feasibility of bringing forward outpatient review and CR in order to facilitate recovery.

      CABG is usually performed through a cut in the breastbone (median sternotomy) and patients
      are required to refrain from upper body exercises, lifting of heavy objects and usual
      strenuous activities for 12 weeks. These restrictions, called "sternal precautions" (SP), are
      intended to aid healing of the cut breastbone. CR which has significant short- and long-term
      benefits after CABG is therefore delayed. The delay can mitigate the benefits of CR,
      contribute to physical deconditioning, and hinder the ability of CR to facilitate timely
      recovery of fitness and physical activity status. According to the 2013 UK national audit of
      CR, late CR commencement contributes to a substantial number of heart surgery patients
      declining to participate in CR. Current time frames for postoperative review and CR are not
      evidence-based and may prolong recovery after CABG, and be placing unnecessary limitations on
      patient activity.

      The standard access for heart operations is through a median sternotomy. In the UK, heart
      operations have steadily increased since 2010. Of 36,134 operations performed in 2013, 17,630
      were isolated CABG. Following CABG, the recovery pathway after hospital discharge has two
      important elements, namely; outpatient review and CR.

      First postoperative outpatient review: It is routine practice to undertake the first
      postoperative review six weeks after hospital discharge. However, high rates of hospital
      readmissions for surgery-related complications within this period have been reported. The
      investigators conducted a prospective observational study (FORCAST6) to investigate
      postoperative morbidity during, as well as patient opinion about, the six-week interval
      between hospital discharge and first review. This study showed that 44% of patients reported
      surgery-related complications; 17.5% required hospital readmission. Although majority of
      patients who did not have complication were satisfied with the six weeks interval, 41% felt
      it was too long. Early contact with patients has been associated with reduction in hospital
      readmissions. Non-randomised studies have also shown lower 30-day adverse outcomes with early
      review, for heart and other surgical patients.

      Outpatient exercise-based cardiac rehabilitation: In current practice, CABG patients commence
      CR from eight weeks after hospital discharge. Current guidelines for activity and exercise
      after median sternotomy have been described as restrictive, conflicting, sometimes arbitrary,
      frequently anecdotal and occasionally based on expert opinion [6]. There are variations in
      types of exercises permitted, limits for weight of objects that can be lifted, guidelines for
      activities, and timeline for resumption of driving. Parker et al demonstrated that the force
      elicited on the breastbone by coughing far exceeded lifting above the recommended limit.
      Adams and colleagues investigated forces associated with 32 activities of daily living and
      reported that the majority not restricted by SP, such as opening and closing doors, generated
      forces greater than the weight limit allowed. While SP may help to support bone healing, the
      optimal nature and duration are unclear especially since sternal bone healing occurs by five
      weeks. A prior observational study (FORCAST6) by the investigators showed that the incidence
      of postoperative complications is highest in the first week after hospital discharge and
      declines to lowest levels by 4 weeks. CR can therefore be safely commenced 5 weeks after
      surgery (4 weeks after hospital discharge).

      Early initiation and progressive physical exercise after heart surgery have well known
      benefits and prolonged restrictions of physical activities appear detrimental to patient
      health and wellbeing. LaPier et al reported functional limitation following sternotomy and
      related this to surgeon-dictated SP. A small observational study noted that functional
      recovery to pre-surgery levels was achievable at two months with physical therapy.
      Improvement in post sternotomy symptoms is also associated with physical activity. The timing
      of CR impacts functional recovery and level of physical fitness after heart surgery. The
      National Audit of CR 2015, recommends early commencement of CR which has become standard
      practice after coronary artery stents or heart attack.

      A delay in starting CR can prolong the recovery process, increase dependence on family and/or
      carers and can cause frustration. This may contribute to anxiety and depression that is
      reported in patients recovering after CABG.

      Published data is lacking about the appropriate timing of postoperative review and CR
      following CABG. The dominant role of SP as a deterrent to early CR after heart surgery has
      been questioned. Cahalin and associates identified major setbacks with current SP practice to
      include; lack of supporting evidence, variation between institutions, lack of universally
      accepted definition, and the functional limitations they engender. A similar experience was
      reported in Europe and Australia. These inconsistencies create a dilemma for patients, their
      families, and healthcare professionals alike. Nevertheless, SP continues to inform
      conventional practice and recommendations of The British Heart Foundation.

      Study goals and objectives

      This study aims to establish the feasibility of delivering and evaluating a definitive RCT
      of; current 8th week versus 4th week CR commencement pathways, reducing the period over which
      patients are required to refrain from usual physical activities.

      Objectives

        1. To determine the feasibility of delivering outpatient review three weeks after discharge
           post CABG, followed by CR from four weeks.

           To achieve this, the study will:

             -  Collect qualitative data through interviews, diary entries and focus group meeting
                with key research and clinical staff.

             -  Identify any organisational, operational and clinical barriers documented by
                research staff.

             -  Identify additional costs or cost savings associated with the proposed pathway.

        2. To test the feasibility of running a fully powered RCT comparing current with the
           proposed pathway.

           This will include:

             -  Assessing surgeons' willingness to conduct outpatient review three weeks after
                discharge and refer patients to CR, from research staff records.

             -  Examining barriers to patient enrolment using contemporary record of the consent
                process, by research staff.

             -  Identifying recruitment rates and drop-out to follow-up.

             -  Identifying the most appropriate outcome measures.

             -  Testing follow-up procedures and data collection tools and management.

             -  Planning the economic evaluation that would accompany the definitive RCT.

             -  Gathering outcome data for power and sample size calculations for the RCT.

        3. To inform any necessary redesign of a new recovery pathway in light of information
           gained from the above.

      Research Questions

        1. What are the barriers and facilitators to providing the proposed pathway, as these will
           be multi-faceted and context specific?

        2. Will the proposed pathway lead to better physical fitness and quality of life after
           CABG, compared to current practice?

        3. What would be the barriers to conducting a RCT to determine clinical and economic
           benefits of the proposed pathway?

        4. What would be the key outcomes for a definitive RCT, and how would they best be
           measured?

      Study design

      This is a feasibility study designed as a Randomized Controlled Trial using mixed
      quantitative and qualitative methods.

      It is a feasibility study where, early review is conducted three weeks after hospital
      discharge following coronary artery bypass grafting (CABG), and CR from 4 weeks. This will be
      a multi-centre RCT of 100 patients comparing the proposed pathway with conventional practice.

      Due to lack of literature in this area; unknown physician and patient acceptability of the
      intervention and the intervention's influence on recruitment and retention, this trial has
      been designed as a mixed methods study.

      Study sites

      Patients will be recruited at Castle Hill Hospital (Hull and East Yorkshire Hospitals NHS
      Trust), the main study site, and James Cook University Hospital, Middlesbrough (South Tees
      Hospitals NHS Foundation Trust).

      The York Trials Unit (YTU) at University of York will be responsible for project and data
      management for this study.

      Study details

      Enrolment: A Research Nurse will approach prospective patients who are admitted for CABG
      through a median sternotomy, and provide them with an information sheet explaining the
      research. The patients will be encouraged to read the information and make a decision about
      participation prior to hospital discharge. Study patients will undergo surgery as normal and
      receive standard in-hospital postoperative care.

      From the 4th day after surgery, the medical staff will screen prospective participants for
      eligibility by review of the results of routine clinical examination including sternal
      stability, and postoperative day 4 tests, namely: electrocardiogram, chest x-ray, full blood
      count, blood biochemistry, and transthoracic echocardiography when clinically indicated. The
      Research Nurse will obtain informed consent from eligible and willing patients, administer
      EuroQol five dimensions (EQ-5D-5L) questionnaire and request cardiopulmonary testing (CPEX)
      for the first 50 patients that are recruited. Patients' baseline data including data from
      these tests will be collected at enrolment.

      Allocation: Enrolled patients will undergo 1:1 randomisation to either; current (control arm)
      or the proposed pathway (intervention arm). Randomisation will be undertaken using a
      centralised randomisation service provided by a York Trials Unit statistician not involved in
      recruiting patients, and will be stratified by site using randomly permuted variable block
      sizes.

      Study intervention: Control (current pathway) - postoperative outpatient review 6 weeks after
      hospital discharge, followed by commencement of CR from 8 weeks. Intervention (proposed
      pathway) - postoperative outpatient review 3 weeks after hospital discharge, followed by
      commencement of CR from 4 weeks. The structure of outpatient review and CR will be the same
      for both arms of the trial, as in current practice, specifically:

        1. First postoperative outpatient review: Specialist surgical team will perform
           postoperative outpatient review, as is standard practice, for all study patients.
           Postoperative history, clinical examination including sternal stability, chest x-ray,
           electrocardiogram and medication review will be undertaken and, patients that are
           certified fit for CR would be referred to start CR programme. This review will take
           place at six weeks post hospital discharge in the control arm, and at three weeks in the
           intervention arm. Patients considered unfit for CR will be given a further 3 week review
           appointment and the reason(s) documented.

        2. Outpatient exercise-based CR: Patients referred for CR will be offered a comprehensive
           programme. A first appointment would be made with a cardiac specialist nurse who would
           provide the patients with advice and leaflets on cardiac risk factor reduction. This
           will typically include information on medication, diet, exercise and physical activity
           as well as psychosocial wellbeing and smoking cessation. Patients will be invited to a
           group education session on cardiac risk factor reduction. This will be delivered by
           specialist cardiac rehabilitation staff. At this first appointment, referral to other
           healthcare professionals such as specialist counsellors, pharmacists and dieticians may
           also be considered when necessary. Unless contraindicated, referral to the exercise
           component of the CR programme will be made. Before joining the CR exercise class,
           patients will receive a holistic assessment from a specialist physiotherapist or
           exercise professional. This will involve exercise testing using the incremental shuttle
           walk test (ISWT). This baseline test will help to personalise exercise prescription for
           each patent. Following this assessment, patients will be enrolled in exercise
           programmes. CR exercise training will consist of supervised low-to-moderate intensity
           exercise performed once or twice week for eight weeks (as is standard practice).
           Exercise will be prescribed according to standards published by the British Association
           for Cardiac Prevention and Rehabilitation and, the Association of Chartered
           Physiotherapists in Cardiac Rehabilitation. Exercise training will be performed in a
           gym-like environment with other patients. Interval circuit training is the most commonly
           prescribed mode of exercise with each individual exercise programme tailored to
           patients' specific needs and fitness level. The following equipment will be used; heart
           rate monitors, treadmill, static bikes, and hand weights. At the end of CR, a
           reassessment, including exercise testing using ISWT will be conducted. The pre and post
           CR tests will be recorded. A discharge letter would be sent to patients' General
           Practitioners summarising their treatment.

      The control arm will commence CR at 8 weeks while the intervention arm will start at 4 weeks.

      All study patients and CR staff will be encouraged to complete bespoke CR diaries for the
      duration of CR. Patients will complete EQ-5D-5L questionnaires at the end of CR.

      Sample size

      The research is a feasibility study and therefore does not have a primary outcome measure to
      inform a power calculation. One of this study's objectives is to establish a primary outcome
      and its variability to inform sample size calculations for subsequent research. Sample sizes
      of between 24 and 70 have been recommended for feasibility trials to allow for the reliable
      estimation of a standard deviation for use in future sample size calculations. The
      investigators hope to recruit 100 eligible patients. This will allow for a 30% attrition rate
      to still have 70 patients in the final analysis. There will be a 5 month recruitment period
      across two centres. The two clinical sites each perform over 300 isolated CABG operations
      annually, and it is anticipated that about 200 of these per site will be eligible for the
      study (100 per site over 5 months). The investigators therefore require a participation rate
      of 33% to meet our target sample size. If 300 eligible participants are identified, the
      investigators will be able to estimate a participation rate of 33% to within a 95% confidence
      interval of ±6%.

      Quantitative tests and data collection

      In this study ISWT and CPEX would be used to assess physical fitness. The ISWT is a field
      test and fairly crude measure of aerobic fitness. It is a popular aerobic fitness assessment
      tool in UK CR programmes. For this reason it is important that we use an ecologically valid
      tool to assess aerobic fitness if the findings from our study are to be extrapolated to
      routine clinical practice.

      CPEX is not just a tool to assess aerobic fitness; it is the gold-standard method of
      assessing aerobic fitness and other prognostically important cardiopulmonary variables. CPEX
      generates far more information on the cardiovascular and cardiorespiratory health of patients
      meaning that we can characterise disease severity in a more meaningful way. CPEX produces a
      lot of data that may help explain mechanisms for change which ISWT is not able to yield
      unless we were to use telemetry base VO2 using something like COSMED. CPEX is the most
      accurate method of assessing fitness change. This is potentially important if we are to
      assess the beneficial/not harmful effects of early CR. Furthermore, the ISWT is not yet
      validated for use in the early CR cohorts.

      It is important and worthwhile to collect some data on CPEX in this trial, however, given the
      cost of CPEX this will only be used in the first 25 participants randomised to each group,
      i.e. half our intended sample size.

      The investigators would use the field test (ISWT) for all participants and also assess half
      the intended sample size with CPEX. This will reduce the costs but still give use useful
      information to (1) understand any physiological change and (2) validate ISWT against CPEX at
      baseline testing. This will also help to understand if they are measuring similar attributes
      of fitness.

      Quantitative data will be collected for all the study patients from enrolment to completion
      of follow-up, using:

        -  Case report forms to collect general health and EQ-5D-5L questionnaires at baseline
           (prior to randomisation), completion of CR and 26 weeks after hospital discharge,

        -  Medical records of outpatient clinical review and exit consultation, listing hospital
           readmissions and, attendance at General Practitioners' surgeries and Accident and
           Emergency departments for surgery-related complications.

        -  CR report of exercise testing results (ISWT) at start and end of CR, and at 26 weeks
           post discharge,

        -  CPEX reports at baseline and 26 weeks post discharge The study design provides some
           challenges for collection of comparable data because of the difference in the timings of
           the components of the recovery pathway for the two study arms. For example, data
           collected at outpatient review, beginning and end of CR will be at different times in
           the recovery pathway for the 2 study arms. However changes in the parameters within each
           study arm would yield useful information about the trend. Having considered these
           challenges, the investigators intend to collect similar data for both study arms at
           baseline prior to randomisation and at 26 weeks follow-up, for direct comparison, even
           though late follow-up may carry a risk of high drop-out.

      All data will be anonymised; patients will be identifiable only by a unique trial ID. Data
      collection will be monitored and inconsistencies, validation errors or inaccuracies will be
      followed up.

      Qualitative data recording

      Qualitative data will be collected from patients and, the research and clinical staff
      through:

        -  Face-to-face semi-structured interviews with patients at both the outpatient review and
           follow-up review at 26 weeks. Ten patients in each arm would be interviewed twice, ie 40
           interviews. The topic guides for the interviews will use open ended questions to guide
           respondents to consider their experiences and views of the timing of the outpatient
           review, the offer of CR made to them, and, for the end of study interviews, their
           experiences of attending CR. Interviews will be digitally recorded and transcribed
           verbatim.

        -  Diary entries of patients, Research Nurse and CR staff. Patients would be given a
           bespoke diary that will cover the 8-week period of CR, with tick boxes and free text
           sections. They would be encouraged to make entries on a weekly basis during the 2 months
           of CR. This will capture postoperative complications, their experiences of pain and any
           health-related adverse occurrences during exercise-based CR. The Research Nurse shall
           keep a diary with a record of patients' and surgeons' attitude to recruitment for the
           study.

      CR staff would also keep one diary at each of the 2 centres and will collect information
      about patient drop-outs or opt-outs of CR sessions, level of participation and adverse events
      during the sessions.

      • A focus group meeting of the research and clinical staff involved in the trial would be
      held after the 26 week follow-up period. The focus group topic guide will use open-ended
      prompts to facilitate discussion on both individual and shared views of the CR offer made to
      patients in each treatment arm, and the barriers and facilitators at individual, clinical and
      organisational level associated with each treatment trajectory.

      Safety consideration

      Study patients will undergo clinical assessment after discharge following CABG, and be
      certified fit for CR by the surgical team. Before commencing exercise-based CR they will
      undergo exercise testing, and CR will be tailored to their fitness levels. At completion of
      CR, they would have another assessment and exit consultation. This would enable early
      detection of possible complications such as:

      Sternal pain: Delayed sternal healing by forces or pressure not severe enough to disrupt
      healing contributes to severe pain associated with tenderness along the sternotomy. This may
      be confused with muscular or sternal wire pain, and paraesthesia which are more common.

      Sternal instability: This is abnormal movement between the surgically divided sternum due to
      delayed healing or non-union. This complication is rare.

      Any study patient who complains of sternal wound pain or a feeling of "sternal click" will be
      seen urgently by the surgical staff, examined and investigated appropriately. All adverse
      events will be recorded. Patients who suffer adverse events with causality linked to sternal
      instability will be given appropriate treatment, including surgery if required.

      Follow-up

      At 6 months (26 weeks) after surgery, all study patients will complete EQ-5D-5L quality of
      life questionnaire, have CPEX, undergo ISWT, and have an end-of-study consultation with the
      research staff, who will inquire about details of further medical treatment after hospital
      discharge. Patients will be examined for sternal wound complications, including sternal
      instability.

      Statistical analysis

      Statistical analysis will be undertaken in Stata version 13, or later, by a medical
      statistician at York Trials Unit. The analysis and reporting of this feasibility trial will
      follow CONSORT guidelines and a flow diagram will depict the progression of participants
      through the trial. The number of patients screened, eligible, consenting and randomised will
      be summarised, with reasons for non-participation given where possible. Baseline data will be
      summarised by randomised group. No formal statistical comparisons will be undertaken.
      Continuous variables will be summarised using descriptive statistics (n, mean, standard
      deviation, median, minimum and maximum) while categorical data will be reported as counts and
      percentages. Participant outcomes will be summarised descriptively by randomised group and
      time point, including extent of missing data. As this is a feasibility trial, formal
      hypothesis for effectiveness will not be carried out.

      The number of participants attending their review appointment and entering CR, and the time
      between surgery and these events, will be summarised by treatment group. Questionnaire return
      rates will be presented. Adverse events will be summarised descriptively.

      Qualitative data analysis

      Data will be analysed separately per research grouping ie patients, research staff and
      clinical staff. Data will be analysed using conventional content analysis, with the aim of
      detailing individuals' views regarding the timing of outpatient review, commencement of CR,
      and experiences of attending and undertaking CR.

      Transcribed data from the interviews and focus groups will be downloaded into the qualitative
      data analysis computer software package NVivo, coded and analysed inductively using thematic
      content analysis.

      Interviews: As interviews are to be conducted at two time points, the analysis will compare
      themes both within and across time periods to determine if patients' views and experiences
      differed over time. As patients will be purposively sampled by age, gender and ethnicity, the
      analysis will also aim to identify intersections between these groupings. The findings from
      the patient generated qualitative data will inform the feasibility and acceptability of the
      offer and timing of CR.

      Patient Dairies: The free text data detailing patient's experiences of receiving CR over the
      eight week study period will be subject to thematic content analysis, where the richness of
      the data allows. If data are quite 'thin', an analysis that counts recurring items within the
      text will be used. These data will be triangulated with the themes arising from the patient
      interviews as confirmation or refutation of the findings from those data.

      Focus Groups: The focus group analysis will pay particular attention to the interactions
      between group members and staff groupings in the development of themes, in order to determine
      the barriers and facilitators perceived by staff groups at individual, clinical and
      organisational level within each treatment trajectory.

      Finally, the themes from the patient interviews staff focus groups will be compared to
      determine the similarities and differences between the themes in order to reflect a complete
      picture of the feasibility and acceptability of the offer of early versus late CR.

      In combination these qualitative analyses will be used to inform the development of the
      logistical processes involved in delivering a large-scale multi-centre RCT.

      Economic analysis

      Health economic analysis will be provided by a University of York (Centre for Health
      Economics) health economist. Due to the feasibility nature of the proposed trial the analysis
      will focus on the consideration of questions related to the feasibility of conducting a full
      economic evaluation. Estimates of patient benefit, determined from the EQ-5D-5L will be
      summarised for the two arms of the trial, including the rate of response of relevant
      questionnaires. Exploration of the short and long term NHS resource use related to both
      interventions will be conducted, and relevant sources of informative data required for a full
      scale RCT identified.

      Mortality and adverse event rates will also be monitored to determine the importance of long
      term extrapolation of related outcomes for any future analysis of a full scale RCT. As this
      is a feasibility trial, formal estimation of the cost-effectiveness of the respective
      interventions will not be carried out.
    

Intervention name(s): Change in the timing of components of usual care
Intervention type(s): Other
Intervention description(s): Bringing forward outpatient review, and cardiac rehabilitation after CABG by 3 and 4 weeks respectively.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Coronary Artery Bypass Grafting; Median sternotomy; Post-operative outpatient review; Cardiac rehabilitation; Quality of life