1. to determine if a Phase III RCT of prehab vs usual care for LLDs is feasible (including
           rates of recruitment, adherence, adverse events, and attrition);

        2. to determine what, if any, intervention or trial modifications are warranted for a Phase
           III RCT; and,

        3. to explore estimates of efficacy among donor-centered outcomes (e.g., quality of life,
           physical function, satisfaction with care) that may form the basis for sample size
           calculations of a Phase III RCT.

PRehab tO PreparE Living Liver Donors for Enhanced Recovery

Living Donor Liver Transplantation

Living donor liver transplantation (LDLT) is an established treatment for end-stage liver
      disease.1 Preserving health and quality of life are priorities of care for living liver
      donors (LLD) as they receive no direct medical benefit from their donation.1,2 Unfortunately,
      recent research demonstrates that LLDs experience significant postoperative pain,
      dysfunction, and adverse psychosocial outcomes that may persist up to several years.3-5 Given
      the risks and postoperative sequalae associated with LDLT, potential LLDs must undergo a
      comprehensive and interdisciplinary screening and selection process, including a medical
      history, laboratory assessments, and physical and psychosocial/psychiatric examinations.1
      Yet, despite widely established thresholds for organ donation candidacy, research
      demonstrates that living liver or kidney donors with lower pre-donation physical and mental
      health (e.g., higher BMI, fatigue, less physical activity, smoking, mood and anxiety
      disturbance) are at higher risk for worse physical and mental health, and health-related
      quality of life up to 12 months after donation.6-8 Moreover, some potential donors may lose
      donation candidacy for a variety of reasons, including changes in health, increasing anxiety
      and ambivalence related to the donation, or insufficient support.1,9 Strategies aimed at
      optimizing the mental and physical health for potential LLDs are therefore appropriate for
      both the minimization of surgical risks and preservation of candidate pools, but also, are in
      keeping with the priorities of LDLT - that is, preservation of health and quality of life for
      LLDs.

      Over the last fifteen years, prehabilitation (or 'prehab') has emerged and grown as a
      feasible, safe, and efficacious strategy to improve preoperative health and contribute to
      reductions in surgical complications and adverse postoperative outcomes. Prehab has been
      examined in numerous surgical settings, including oncology10, cardiology11,12, and among
      solid organ transplant recipients.13-16 Prehab research and clinical application have
      generally focused on high-risk surgical candidates in the interest of efficient resource
      allocation given the likelihood for clinically meaningful improvements in outcomes (e.g.,
      reduced surgical complications).17-20 To date, living organ donors have not been targeted
      recipients of prehab given their relatively low surgical risk due to health screening and
      selection. However, this is at odds with the philosophy of care for living donors (i.e., to
      protect against adverse effects) and undervalues the decrement in quality of life that many
      donors endure. Accordingly, research examining the role and effect of prehab for LLDs has
      important health and ethical implications.

      Given that there have been no studies examining the effect of prehab for LLDs, much
      uncertainty remains about whether LLDs will enroll, adhere, and be retained in the
      intervention. Further, while we may surmise what the ideal components of prehab may be for
      LLDs, this has yet to be examined. Finally, there are no studies assessing the feasibility of
      conducting a large scale randomized controlled trial (RCT) of prehab for LLDs that could help
      establish sample sizes, recruitment strategies, and intervention and measurement design
      elements. Thus, in this trial protocol entitled "PRehab tO PreparE Living Liver Donors for
      Enhanced Recovery" (PROPELLER), we propose a feasibility RCT of prehab vs usual care for LLDs
      who are scheduled for LDLT.

Prehabilitation

Prehab to Prepare Living Liver Donors for Enhanced Recovery

i. Recruitment success will be measured by the proportion of participants who are randomized divided by the number of identified eligible LLDs. Reasons for non-participation will be collected. The feasibility target is 40%.
ii. Adherence will be collected on participants attendance and completion of the interventions prescribed iii. The frequency of drop-out during program participation will be documented including reasons for drop-out. The feasibility target for attrition is equal to or less than 15%.
iv. The amount of missing data will be quantified and reported as a feasibility outcome. Data missingness will be reported as the proportion of each outcome measure that is incomplete and per timepoint.
v. Any safety or adverse events related to the prehabilitation intervention or study testing will be reported during weekly telephone calls with participants. Reporting and grading will follow the Common Terminology Criteria for Adverse Events version 5.0.36

Clinician Investigator

Postoperative LOS will be recorded from the participant medical record in days from the time of surgery until hospital discharge, abstracted from the medical record.
ii. Surgical and post-operative complications Complications, including mortality, will be abstracted from the medical record and follow the Clavien-Dindo classification.37 38
iii. Hospital Readmission Any health event that requires readmission will also be documented. This will be recorded during hospitalization and up to 12 weeks postoperatively, derived from the medical record.

Complications, including mortality, will be abstracted from the medical record and follow the Clavien-Dindo classification.

Any health event that requires readmission will also be documented. This will be recorded during hospitalization and up to 12 weeks postoperatively, derived from the medical record.

PREHAB participants will receive a multimodal intervention comprising of exercise, nutrition, and psycho/behavioural/educational support provided by an interprofessional prehab team comprising kinesiologists, dietitians, psychologists, and a previous LLD study partner. To facilitate overall compliance and appropriate adaptation to the home-based intervention components, participants will receive printed material, and a study coordinator will communicate weekly with patients to provide encouragement, monitor adherence, and clarify any questions or concerns.

Usual care participants will be instructed to resume typical lifestyle behaviours until the date of the surgery. To standardize exposure to publicly available resources, usual care participants will receive the 24-Hour Movement Guidelines for Adults,33 Canada's Food Guide,27 a list of stress management resources (website, apps, free reading material), and reference to the Smoker's Helpline.

PRehab tO PreparE Living Liver Donors for Enhanced Recovery

About this trial

Study ID

Status

Type

Phase

Placebo

Accepting

Not accepting

Trial Timing

What is this trial about?

What are the participation requirements?

Locations

Location

Status