Highlights
– In a pragmatic, multicenter RCT of 847 older adults with frailty scheduled for elective noncardiac surgery, offer of a coach-supported, home-based multimodal prehabilitation program did not reduce 30‑day postoperative disability (WHODAS 2.0) or in-hospital complications compared with usual care.
– Median prehabilitation exposure was 4 weeks; no differences in preoperative safety events were observed.
– A per-protocol signal: participants who completed >75% of prescribed exercises had lower postoperative disability, suggesting adherence may be a key mediator of benefit.
– Primary barriers to adherence were competing priorities and motivation, highlighting implementation challenges for home-based models in older adults with frailty.
Background
Prehabilitation—structured exercise, nutritional optimization and behavior change implemented in the preoperative period—aims to increase physiologic reserve to withstand surgical stress and accelerate recovery. Prior explanatory trials and single-center studies in selected surgical populations have suggested prehabilitation can improve preoperative fitness and postoperative outcomes, but results have been heterogeneous and often derive from supervised or center-based programs with intensive resources. Older adults with frailty represent a high-risk surgical population in whom small improvements in physiologic reserve may translate into meaningful clinical benefit. However, the effectiveness of offering a scalable, home-based prehabilitation program across multiple centers in routine practice is uncertain, particularly when adherence and delivery resources vary.
Study design
This pragmatic, parallel-arm, multicenter randomized clinical trial (PREPARE Trial; ClinicalTrials.gov NCT04221295) recruited adults aged ≥60 years with frailty (Clinical Frailty Scale score ≥4) who were scheduled for elective, inpatient noncardiac surgery at 13 Canadian centers between March 2, 2020 and February 8, 2024. Clinicians and outcome assessors were fully blinded; participants were partially blinded—those randomized to usual care received publicly available activity and nutritional guidance. Participants were randomized to receive either usual care or a home-based multimodal prehabilitation program consisting of prescribed exercises and personalized nutritional recommendations with remote, theory-based coaching to enhance adherence. The program was delivered remotely (telephone/virtual), designed for home performance, and tailored to individual capacity. The median duration of enrollment in the prehabilitation program was 4 weeks (IQR 3–7).
The trial had two coprimary outcomes: (1) patient-reported disability 30 days after surgery measured using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0), and (2) incidence of any postoperative complication during the index surgical hospitalization. Analysis used mixed-effects regression adjusted for stratification and prespecified prognostic factors. The trial embedded qualitative work using the Theoretical Domains Framework to identify adherence barriers.
Key findings
Participants and flow: Of 992 eligible participants, 847 (85.4%) were randomized—423 to prehabilitation and 424 to usual care—and 705 ultimately underwent the planned surgery (353 prehabilitation, 352 usual care). Mean age was 71.7 (SD 7.1) years; 53.4% were female. The analysis used intention-to-treat principles for the randomized cohort that underwent surgery.
Primary outcomes
– Disability (WHODAS 2.0) at 30 days: Mean postoperative disability score was 23.5 (SD 21.8) in the prehabilitation group versus 24.7 (SD 23.8) in usual care. The adjusted mean difference was −1.4 (97.5% CI −4.9 to 2.0; P = .36), indicating no statistically significant or clinically important benefit.
– In-hospital complications: Complications occurred in 177 participants (50.1%) assigned to prehabilitation versus 168 (47.7%) in usual care. The adjusted odds ratio (aOR) was 1.05 (97.5% CI 0.73–1.49; P = .78), showing no reduction in the incidence of in-hospital complications with prehabilitation.
Pre-specified secondary and safety outcomes
Preoperative safety outcomes did not differ between groups, and no intervention-attributable safety signals were reported. Secondary outcomes reported included health-related quality of life, survival, falls, complication severity, activities of daily living, length of stay, discharge disposition, lower limb function, and readmission; the primary publication emphasizes null effects on the main endpoints and no safety concerns. Detailed secondary outcome results should be consulted in the original manuscript for effect sizes and confidence intervals.
Adherence and subgroup analyses
Adherence to the home exercise regimen was variable. In an analysis restricted to participants who completed more than 75% of the prescribed exercises, those randomized to prehabilitation experienced lower postoperative disability (mean difference −4.9; 97.5% CI −9.8 to −0.01; P = .02). However, even among high adherers there was no significant reduction in complication incidence (OR 1.06; 97.5% CI 0.67–1.67; P = .79). The qualitative component identified key barriers to adherence, notably competing life priorities and difficulties with motivation—barriers that are plausible contributors to the observed heterogeneity in effect.
Interpretation of effect sizes
The primary null findings indicate that offering a coach-supported, home-based prehabilitation program in routine multicenter practice does not, on average, reduce early postoperative disability or complications among older adults with frailty when compared with usual care augmented by public activity and nutritional guidance. The modest reduction in disability among high adherers suggests a dose–response relationship between intervention exposure and functional outcome, but causality cannot be assumed because adherent participants may differ in unmeasured ways (motivation, baseline function, social support).
Expert commentary and contextualization
This trial addresses an important translational gap: many prior positive studies of prehabilitation were explanatory, single-center, or relied on supervised, facility-based programs with high resource intensity and selected participants. PREPARE tested a pragmatic, scalable model—remote coaching for home exercise and dietary advice—across multiple surgical services and centers, capturing real-world constraints such as limited preoperative time and competing patient priorities. The negative primary result does not negate the biological plausibility that improving muscle strength, aerobic capacity, and nutritional status before surgery could improve outcomes; rather, it highlights implementation barriers.
Key contextual points:
– Timing and dose: Median prehabilitation exposure was 4 weeks. Physiologic adaptations—particularly gains in aerobic capacity and muscle mass—often require longer duration or higher intensity training; brief preoperative windows may limit achievable biologic effect.
– Delivery model: Remote, home-based programs improve scalability but can suffer from variable adherence. Supervised or hybrid models (initial supervision, targeted in-person sessions) may enhance fidelity and outcomes but increase resource needs.
– Population heterogeneity: The trial enrolled older adults with a Clinical Frailty Scale ≥4, spanning mild to moderate frailty. The intervention may be most effective in narrowly defined subgroups (e.g., those with sarcopenia, severe deconditioning) or in procedures with high physiologic demand.
– Outcomes selection: WHODAS 2.0 captures global disability and is patient-centered, but some proponents argue hard endpoints (pulmonary complications, LOS, discharge destination) or longer-term functional measures might capture benefits missed at 30 days.
These contextual factors suggest that a one-size-fits-all, home-based offer may be insufficient; targeted, adequately dosed programs with strategies to improve adherence may be necessary to realize benefits in frail older adults.
Limitations and generalizability
Limitations to consider when applying these findings:
– Adherence and contamination: The control arm received publicly available guidance, and adherence in the intervention arm was variable, limiting the ability to evaluate the effect of delivered (versus offered) prehabilitation.
– Preoperative interval: Variable surgical scheduling and limited lead time constrained program duration in many participants.
– Heterogeneous surgeries: The trial included a broad range of elective noncardiac inpatient surgeries; effects may differ by surgical type and physiologic stress.
– Per-protocol inferences: The apparent benefit among high adherers may be biased by confounding (adherers likely differ from nonadherers in motivation and baseline health).
Despite these limitations, the multicenter pragmatic design enhances external validity for real-world implementation in publicly funded health systems and among older adults with frailty.
Implications for practice and research
For clinicians and health systems:
– Routine offer of a low-intensity, home-based prehabilitation package with remote coaching may not, by itself, reduce early postoperative disability or complications among older adults with frailty.
– When prehabilitation is considered, prioritize strategies to maximize adherence (motivational interviewing, caregiver involvement, scheduled supervised sessions), target patients most likely to benefit, and ensure adequate preoperative duration and intensity where feasible.
For researchers and policymakers:
– Future randomized trials should test pragmatic strategies to improve adherence (hybrid supervised/remote models, digital engagement tools, integrated perioperative care pathways) and identify subgroups most likely to benefit (e.g., sarcopenic patients, severe deconditioning, specific high-risk procedures).
– Implementation science approaches are needed to address real-world barriers—competing priorities, limited motivation, and resource constraints—documented in the qualitative findings of this trial.
– Economic evaluations and longer-term outcome assessments (90 days to 1 year) will help determine value and sustainability of prehabilitation models.
Conclusion
The PREPARE trial provides high-quality, pragmatic evidence that offering coach-supported, home-based multimodal prehabilitation to older surgical patients with frailty did not reduce 30‑day postoperative disability or in-hospital complications compared with usual care. The absence of safety signals is reassuring. A signal of improved disability among participants who achieved high adherence suggests that delivered dose and engagement matter, but real-world barriers—time, motivation, competing priorities—must be overcome for home-based models to realize potential benefits. Implementation strategies that increase adherence and targeted approaches that select patients and procedures with the highest likelihood of benefit deserve priority in future research.
Funding and trial registration
For funding details and full author disclosures, please consult the original publication. Trial registration: ClinicalTrials.gov Identifier NCT04221295.
References
1. McIsaac DI, Lee S, Fergusson D, et al; PREPARE Trial Investigator Group. Home-Based Prehabilitation for Older Surgical Patients With Frailty: A Randomized Clinical Trial. JAMA Surg. 2025 Dec 3:e255288. doi:10.1001/jamasurg.2025.5288. PMID: 41335421; PMCID: PMC12676472.
2. Rockwood K, Song X, MacKnight C, et al. A global clinical measure of fitness and frailty in elderly people. CMAJ. 2005;173(5):489-495. doi:10.1503/cmaj.050051.
3. Üstün TB, Kostanjsek N, Chatterji S, Rehm J, editors. Measuring Health and Disability: Manual for WHO Disability Assessment Schedule (WHODAS 2.0). World Health Organization; 2010.
