Clinical trial NCT04221295: The PREPARE Trial: Exercise Before Surgery to Improve Recovery in Older People With Frailty
Official title: PREPARE Trial: a Parallel Arm Multicenter Randomized Trial of Frailty-focused PReoperative Exercise to Decrease PostoperAtive Complications Rates and Disability scorEs
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Frailty
Surgery--Complications
Disability Physical
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
First posted: 2020-01-09
Enrollment: 850
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study evaluates whether participating in a home-based exercise program leads to lower levels of complication rates and patient-reported disability after surgery. Half of the participants will be randomized into the exercise group, while the other half will be randomized into the control group.

Detailed description: Background: Four out of ten older people having surgery live with frailty, leaving them vulnerable to adverse outcomes due to accumulation of age- and disease-related deficits. An increasing number of people with frailty require surgery. Frailty is associated with a \>2-fold increase in complications and new patient-reported disability; absolute rates are \>50% and 20% respectively; physical and physiologic deficits are particularly implicated. Mortality, costs and institutionalization after surgery are also significantly associated with frailty.

Despite frailty's strong association with adverse outcomes, few perioperative trials include older people with frailty. Exercise therapy may improve function and decrease complications for other people with frailty by addressing physical and physiologic deficits. However, existing trials are small (median n=54) and single center. Most interventions have been resource-intensive, requiring attendance at hospital-based sessions, which may limit access to many who could benefit. Patient-reported outcomes are also lacking. Therefore, a multicenter trial of home-based exercise therapy before surgery for older people with frailty, powered to address patient-reported outcomes, is needed. Our trial will address these knowledge gaps by testing the effectiveness of home-based preoperative exercise (exercise prehabilitation) in decreasing patient-reported disability and postoperative complications in older people with frailty having major surgery.

Research aims: Estimate the effectiveness of exercise prehabilitation on:

* Co-primary outcomes: patient-reported disability 30-days after surgery and in-hospital complications
* Secondary outcomes: patient-centered (discharge home, survival, 30, 90 and one-year disability scores, quality of life, function) and system-relevant (length of stay, admissions)
* Health economic outcomes: costs, cost-effectiveness

Methods:

Design, setting and participants: Parallel-arm multicenter randomized controlled trial at 11 Canadian hospitals. People =\> 60 years old with frailty (Clinical Frailty Scale score of 4/9) having major elective non-cardiac surgery (vascular, intrathoracic, intraabdominal, pelvic, ENT) with expected length of stay of =\> 2 days will be included.

Intervention: Home-based exercise program with demonstrated efficacy, feasibility and acceptability tailored for people with frailty.

Outcomes and sample size: Co-primary outcomes are patient-reported disability 30 days after surgery (validated WHODAS tool) and prospectively collected in-hospital complications (validated POMS tool). 750 participants (375/arm) will provide 98% power for disability (control mean score 35 (SD 25; MID=8)) and 90% power for complications (55% complication rate (25% relative risk reduction)) (α=0.025; 2 pair-wise comparisons).

Due to surgical delays and cancellations as a result of the COVID-19 pandemic, our trial sample size has seen more participants having surgery outside of their expected time to operation than originally predicted. To account for this, and to ensure adequate power for our analyses, our final sample size will be increased to 850 participants.

Expertise: Our team features multidisciplinary clinical and methodological experts, nationally representative knowledge users and patient representatives.

Expected outcomes: Older people with frailty are a growing and vulnerable segment of the surgical population and are under-represented in existing studies. Exercise prehabilitation is a high-priority research question which may be most relevant to people with frailty given their physical and physiologic vulnerabilities. This study, featuring patient-reported outcomes and an integrated knowledge translation approach will produce generalizable findings directly relevant to patients, families, caregivers, and knowledge users.

Eligibility criteria: Inclusion Criteria:

* 60 years of age or older
* Elective surgery with expected post-surgery stay of 2 days or more.
* Frailty present (Clinical Frailty Scale (CFS) score of 4/9 or greater)
* Surgery date between 3 and 12 weeks from enrollment

Exclusion Criteria:

* Inability to speak English or French
* Co-morbidity preventing assessment or understanding of questionnaires
* Unable to be contacted by telephone
* Unwilling to participate in exercise program
* Cardiac, neurological or orthopedic procedure
* Palliative surgery
* Certain cardiovascular conditions

Primary outcomes:
measure: In-hospital complications
timeFrame: up to 30 days.
measure: Patient-reported disability 30 days after surgery
timeFrame: Assessing change in score from baseline data collection to 30 days post-op
Secondary outcomes:
measure: Function - 5 Times Sit to Stand
timeFrame: Assessing change in score from baseline data collection up to 30 days post-op.
measure: Function - Daily and total step count
timeFrame: Assessing the difference in daily and total step count between the exercise group and control group for 30 days post-op.
measure: Function - Katz Index of Activities of Daily Living
timeFrame: Assessing change in the participants KATZ ADL score from baseline to post-op day 3, 5, 7 and up to 30 days.
measure: Function - Falls
timeFrame: Assessing the difference in the occurrence of falls between the exercise group and control group on day 3, 5, 7, up to 30 days, as well as 30-day, 90-day and one-year after surgery.
measure: Health-related quality of life
timeFrame: Assessing any change from baseline to 30, 90 and 365 days post-op.
measure: All-cause mortality
timeFrame: 30, 90, and 365 days.
measure: Health System - Discharge disposition
timeFrame: Up to 30 days post-op.
measure: Health System - Hospital re-admissions
timeFrame: 30, 90, and 365 days post-op via telephone
measure: Health System - Emergency department visits
timeFrame: 365 days post-op
measure: Health System - Long-term care admissions
timeFrame: 30, 90, and 365 days post-op via telephone
measure: Participant Feedback
timeFrame: Participants are asked to reflect on the program during a call the day before surgery.
measure: Safety (Adverse Events)
timeFrame: Assessing frequency of, or change in any safety events from enrollment up to 30 days post-op in hospital between the exercise group and control group.
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
Study officials:
affiliation: The Ottawa Hospital Research Institute
name: Daniel I McIsaac, MD,MPH,FRCPC
role: PRINCIPAL_INVESTIGATOR
References:
citation: McIsaac DI, Fergusson DA, Khadaroo R, Meliambro A, Muscedere J, Gillis C, Hladkowicz E, Taljaard M; PREPARE Investigators. PREPARE trial: a protocol for a multicentre randomised trial of frailty-focused preoperative exercise to decrease postoperative complication rates and disability scores. BMJ Open. 2022 Aug 8;12(8):e064165. doi: 10.1136/bmjopen-2022-064165.