The PREPARE Trial: Exercise Before Surgery to Improve Recovery in Older People With Frailty

Frailty Clinical Trial

Official title:

PREPARE Trial: a Parallel Arm Multicenter Randomized Trial of Frailty-focused PReoperative Exercise to Decrease PostoperAtive Complications Rates and Disability scorEs

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04221295
• Other study ID #: 20190409-01T
• Status: Active, not recruiting
• Phase: N/A
• Start date: February 24, 2020
• Est. completion date: May 30, 2025

Study information

• Verified date: April 2024
• Source: Ottawa Hospital Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 850
• Est. completion date: May 30, 2025
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Disability Physical
• Frailty
• Surgery--Complications

Intervention

Behavioral:
• Exercise Group
Previously described in the arm/group descriptions.

Locations

Country	Name	City	State
Canada	The Ottawa Hospital	Ottawa	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Ottawa Hospital Research Institute

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	In-hospital complications	The Postoperative Morbidity Survey (POMS), will be used to define complications. Individuals experiencing any POMS complication or dying in hospital will be said to have experienced a complication.	up to 30 days.
Primary	Patient-reported disability 30 days after surgery	The World Health Organization Disability Assessment Schedule 2.0 (WHODAS) will be used . It is a patient-reported disability scale that assesses limitations in six major life domains - cognition, mobility, self-care, social interaction, life activities and participation in society. Participants will report if they have had no difficulty, mild difficulty, moderate difficulty, severe difficulty or extreme difficulty (simply cannot do) with the items listed.	Assessing change in score from baseline data collection to 30 days post-op
Secondary	Function - 5 Times Sit to Stand	The 5 Times Sit to Stand is a validated test that will be used for measuring the risk of falls and predicting disability in older adults.	Assessing change in score from baseline data collection up to 30 days post-op.
Secondary	Function - Daily and total step count	Daily and total step counts will be measured, which will predict adverse post-hospitalization outcomes and will reflect physical recovery. They will be recorded daily for the duration of the exercise program (for those in the exercise group) and 30 days after surgery (for all participants) to evaluate functional recovery.	Assessing the difference in daily and total step count between the exercise group and control group for 30 days post-op.
Secondary	Function - Katz Index of Activities of Daily Living	The Katz Index measures function in activities of daily living (ADL). The ADLs examined are bathing, dressing, toileting, transferring, continence and feeding. If a person is able to perform the ADL independently, they receive 1 point for that activity. If a person is dependent on others to perform the ADL, they receive 0 points for that activity. A score of 6 is high, meaning the person is independent whereas a score of 0 is low, indicating that the person is very dependent.	Assessing change in the participants KATZ ADL score from baseline to post-op day 3, 5, 7 and up to 30 days.
Secondary	Function - Falls	Falls will be documented as a way of assessing function.	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.
Secondary	Health-related quality of life	EQ-5D EuroQuoL will be used to measure health-related quality of life at baseline, 30, 90 and 365 days after surgery and to inform incremental cost per quality-adjusted life year gained. Participants are asked to select one answer under each domain (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Responses range from having no problems with a particular domain to being unable to engage in that particular domain. Finally, participants are asked to identify on a scale of 0-100 how good or bad their health is on that given day (0 being worst health they can imagine, 100 being best health they can imagine).	Assessing any change from baseline to 30, 90 and 365 days post-op.
Secondary	All-cause mortality	All deaths and death dates will be identified in-hospital or through telephone follow-up.	30, 90, and 365 days.
Secondary	Health System - Discharge disposition	Assess where the participant will be discharged to once out of hospital.	Up to 30 days post-op.
Secondary	Health System - Hospital re-admissions	Participants will be asked during the 30 day, 90 day and one-year follow-up calls if they have been readmitted to hospital since hospital discharge.	30, 90, and 365 days post-op via telephone
Secondary	Health System - Emergency department visits	Emergency department visits since hospital discharge will be captured in the year after surgery	365 days post-op
Secondary	Health System - Long-term care admissions	Participants will be asked during the 30 day, 90 day and one-year follow-up calls if they were admitted to a long-term care facility.	30, 90, and 365 days post-op via telephone
Secondary	Participant Feedback	A theoretical domains framework participant survey will identify barriers and facilitators to participation in the exercise group. Responses are on a five-point likert scale ranging from "strongly disagree" to "strongly agree", or "never" to "always" depending on the question asked.	Participants are asked to reflect on the program during a call the day before surgery.
Secondary	Safety (Adverse Events)	Falls, cardiac or respiratory complications and unplanned healthcare encounters will be collected during the exercise treatment period for the exercise group. For the control group, participants will be asked if they experienced any falls since the time of enrollment up until the day before surgery. Safety data will also be collected should any adverse event take place during any physical assessment data collection time point. Unplanned healthcare encounters will also be collected during the time of enrollment to the day before surgery for the intervention group through chart review.	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.