ExaLT

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HOME-BASED EXERCISE AND MOTIVATIONAL PROGRAMME BEFORE AND AFTER LIVER TRANSPLANTATION

A PHASE IIb, RANDOMISED-CONTROLLED, TWO-CENTRE CLINICAL TRIAL ON THE EFFICACY OF A HOME-BASED EXERCISE AND MOTIVATIONAL PROGRAMME IN PATIENTS BEFORE AND AFTER LIVER TRANSPLANTATION

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ExaLT is now open to recruitment! Keep checking here for relevant updates.

Background

Liver disease, the third commonest cause of death in the UK, predominantly kills between the ages of 18 and 65. This leads to the loss of 62,000 years of working life each year in the UK. Liver transplantation (LT) remains the only curative treatment for patients with liver failure and the number of transplantations in the UK has risen in recent years. LT is a highly resourced intensive procedure requiring a large investment of healthcare resources. The average cost per procedure is estimated at over £1.1m, which includes pre-LT work-up, surgery, perioperative care, and an estimated seven year postoperative follow-up (https://www.nsd.scot.nhs.uk/publications). Complications whilst on the waiting list and in the perioperative period contribute substantially to this cost, and their likelihood is increased markedly by the presence of physical frailty (Lai et al., 2014; Patel et al., 2016 & Son et al., 2018).

 LT exerts a phenomenal physiological and psychological stress on recipients who are frail as a result of long-standing liver failure. Post LT readmission rates are around 50% (Patel et al., 2016) and perioperative complications can lead to reduced long-term quality of life (QoL) and delayed/reduced return to productive employment (Onghena et al., 2016; Saab et al., 2007). End-stage liver disease can lead to skeletal muscle sarcopenia which contributes to a high prevalence (70%) of physical frailty (Sinclair et al., 2016). Frailty both before and after LT is associated with poor psychological and physical health-related QoL (Painter etal., 2001; Tapper et al., 2018 & Derck et al, 2015) which is itself an independent predictor of mortality (Macdonald et al., 2019). Although the majority of patients are under 65 years old, fewer than 50% return to employment, which is largely attributed to prolonged disability/frailty.(Saab et al., 2007)

 Trial Rationale

Exercise interventions have been shown to be effective in other fields of medicine including prior to elective major surgery. However, due to the life-threatening, multi-systemic effects of end-stage liver disease, patients awaiting LT are often perceived as ‘too sick’ to exercise by healthcare professionals and the patient/carers themselves (PPI/Expert observations); with virtually no published data to support the benefits and safety of exercise in this cohort. Effective exercise interventions that reduce frailty pre- and post-LT have the potential to improve clinical outcomes and long-term QoL for this patient group, leading to cost savings for the NHS. Furthermore, a better understanding of how exercise works (i.e. on the muscular and cardiopulmonary systems) and how it can be effectively delivered (i.e. motivational approach adopted) in this unique cohort, will guide future exercise prescriptions (‘type’, ‘dose’, ‘duration’, ‘motivational strategies’) that are required to maximise the efficiency and longevity of this life-changing surgery. In an environment of substantial NHS resource limitation, identifying simple, cost-effective and remotely monitored home-based interventions should be a priority in those patients who may benefit the most.

Design

ExaLT is a phase 2b, open-label, two-centre randomised controlled clinical trial (RCT), with 1:1 individual participant randomisation.

Aim of the Study

The primary aim is to investigate whether a remotely monitored ‘home-based exercise and theory-based motivation support programme’ delivered by physiotherapists before and after liver transplantation (LT) improves quality of life in LT recipients compared to a control group using a patient ‘exercise’ advice leaflet. There are various secondary aims which will also be investigated. 

Setting

The ExaLT Trial will be based at the LT units of the Queen Elizabeth University Hospital, Birmingham (QEUHB) and the Royal Free Hospital, London (RFH).

Target Population

Adult patients (aged 18 years and over) who are awaiting a cadaveric, primary liver transplantation. A total sample size of 266 patients, 133 patients in each arm.

Intervention

Eligible participants will be randomised 1:1 to receive either,

  • Group 1: Intervention group. Remotely-monitored home-based exercise and theory-based motivation support programme whilst on the LT waiting list ( max. 12 months) through to 24 weeks post-LT.
  • Group 2: Control group. Patient exercise advice leaflet before and after LT. The interventions will be delivered to the participants in two phases: phase 1 pre-LT (maximum 52weeks) and phase 2 post-LT (24 weeks).

The study intervention will be of variable duration pre-LT, due to the unpredictable nature of the timing of LT. All patients that are transplanted within 52 weeks of randomisation will receive a fixed 24 week intervention after LT.

Group 1 and 2 will contain approximately the same proportion of age groups, disease severity (UKELD), gender, trial site and participation rates in the ‘muscle sub-study’ as a result of minimisation.

Measurement of outcomes

The primary outcome measure is the physical component score (PCS) from the short form-36 version 2.0 (SF-36v2) health-related QoL questionnaire at 24 weeks post LT.

The ‘key’ secondary outcome measure is the CCI at 24 weeks post LT.

The other secondary outcome measures to be assessed at 24 weeks post LT (*unless stated) include.

  • MCS score of SF-36v2 health-related QoL questionnaire
  • Liver Frailty Index (LFI), Duke Activity Score Index (DASI)
  • Pre-LT morbidity (UKELD, MELD-Na, hospital admissions) and mortality (*assessed up to day of LT)
  • Post-LT length of ICU/hospital stay and hospital re-admissions (frequency, duration [days])
  • Post-LT 30, 90, 180 and 365 day mortality
  • Habitual physical activity levels (daily time spent in light, moderate and vigorous intensity physical activity)
  • “Dose” of exercise completed (measure of the frequency, intensity and duration of exercise)
  • Adherence to HBEP (intervention arm only)
  • Perceptions of the health care climate (how need supportive/empowering the physiotherapist is)
  • Basic psychological need satisfaction (i.e. feelings of autonomy, relatedness, competence)
  • Self-determined motivation to exercise

Eligibility Criteria

Inclusion criteria

  • Adult patients (aged 18 years and over)
  • Awaiting a cadaveric, primary LT at two LT centres: QEUHB and RFH.
  • Being an out-patient at the time of baseline trial visit (consent)

Exclusion criteria

  • Patients awaiting super-urgent LT, multi-organ transplantation, live-related donor LT, regraft LT
  • Inability to safely comply with the exercise intervention due to:
    • severe hepatic encephalopathy
    • oxygen-dependent hepato-pulmonary syndrome
  • Patients without liver failure including:
    • liver cancer in the absence of cirrhosis
    • polycystic liver disease
    • rare metabolic/genetic conditions.
  • Patient refuses or lacks capacity to give informed consent to participate in the trial, at the point of study visit 1 (baseline)

More information...

IRAS ID: 295426

Sponsor: The University of Birmingham

Sponsor reference: RG_21-164

Funder: NIHR EME Programme