Multimodal Prehabilitation for Surgery in the Elderly: A Randomised, Prospective, Multicenter, Multidisciplinary Trial

Study Overview
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Brief Summary
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This multicentric, randomised controlled trial is to the investigators knowledge the first implementation of a multimodal, multidisciplinary prehabilitation approach using knowledge from different specialties to lower complications and to increase cost effectiveness after major surgery in elderly, frail patients.

Detailed Description
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Postoperative complications occur in up to 50% of patients and major surgery is associated with a 20 to 40% reduction in physiological and functional capacity. The elderly have surgery 4 times more often than the rest of the population, thus in the future a major proportion of patients presenting for surgery will be older than 65 years. Elderly patients have more postoperative complications, a longer convalescence and higher surgical morbidity and mortality. The number and severity of complications are closely related to preoperative functional capacity, nutritional state, psychological state, and smoking behavior. Another population most probably to benefit from such a program are cancer patients with decreased functional health after cancer treatment. Cancer prehabilitation affords an opportunity for the patient to improve functional status while waiting to begin treatment. This is a patient group expected to grow in the future. This is a multicenter, multidisciplinary, 2 arms (standard, n=233 vs intervention i.e. prehabilitation, n=233), randomised controlled trial (RCT). The prehabilitation program is composed of 4 elements: exercise training, nutritional intervention, correction of anaemia and smoking cessation. This multicentric, randomised controlled trial is to the investigators knowledge the first implementation of a multimodal, multidisciplinary prehabilitation approach using knowledge from different specialties to lower complications and to increase cost effectiveness after major surgery in elderly, morbid patients. The primary outcome is measured by the comprehensive complication index (CCI). Secondary outcomes are physical parameters measured by cardio-pulmonary exercise testing (CPET), grip strengh, Nutritional Risk Score (NRS). Further outcomes are amongst others smoking behavior, haemoglobin concentration, days at home at 30 days (DAH30) and quality of recovery 15 (QoR15).

Official Title
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Multimodal Prehabilitation for Major Surgery in Elderly Patients to Lower Complications and to Increase Cost Effectiveness: A Randomised, Prospective, Multicenter, Multidisciplinary Trial (PREHABIL Trial).

Conditions
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Frail Elderly Syndrome, Major Surgery

Intervention / Treatment
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* Procedure: Multimodal Prehabilitation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent comorbid (≥ASA 3) pre-existing fitness deficit: AT<11ml/kg/min respectively VO2peak<14ml/kg/min if AT unavailable or VE/VCO2 slope > 33 scheduled for major urologic, thoracic, visceral, orthopaedic or cardiovascular surgery screening at least 2 weeks prior to surgery Exclusion Criteria: Paralysis or patients with mobility problems (who are unable to exercise), Premorbid conditions or orthopaedic impairments that contraindicate exercise, Cognitive disabilities, Chronic renal failure (need for dialysis) Emergency procedures.

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, parallel group, multi-centre, multidisciplinary, active controlled trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Patients that meet the inclusion criteria will be randomised and scheduled for surgery at least 2 weeks after the diagnosis/decision to proceed to surgery. This timeframe allows the implementation of a minimal 2 weeks (up to 4 weeks) multidisciplinary prehabilitation program. Prehabilitation program is composed of 4 elements: exercise training, nutritional intervention, correction of anaemia and smoking cessation. An individual treatment strategy will be proposed to the patient by a multidisciplinary team consisting of surgeon, anesthesiologist, dietitian and physiotherapist. | Procedure: Multimodal Prehabilitation<br>* A multimodal prehabilitation program (exercise, nutrition, anemia correction and smoking cessation).<br>|
| No Intervention: Control<br>Perioperative care of the control group will be based on standardized, multi-element, ERAS recommendations as already implemented in the different participating clinics. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comprehensive Complication Index (CCI) | The comprehensive complication index (value from 0 = no complication to 100 = death) is a valuable, validated index for the assessment of multiple postoperative complications. It has been developed based on Swiss hospital data and has been validated internationally. | 30 days after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular & Pulmonary | Cardio-Pulmonary Exercise Test (CPET): Peak VO2, VO2 at VT1, peak VE, VE/VCO2 slope, O pulse, FEV1, FEV1/FVC, resting HR, HR reserve, resting systolic and diastolic BP, CPAx ICUD and CPAX HosD in case of ICU admission, Maximum inspiratory pressure , Grip strength, NTproBNP, serial hsTroponin in case of raised NTproBNP, change in preoperative P-POSSUM score | Before and after 2-4 weeks of prehabilitation, at 30 days | 
| Nutrition & Bioimpendance | Nutritional Risk Score (NRS), Bio impedance: weight, muscle mass, fat mass, percent body fat, extracellular water/intracellular water, and phase angle, Fat Free Body Mass (FFM) and Lean body Mass (LBM), Days nil per mouth | At the beginning of study, before and after surgery, at 30 days. | 
| Anaemia | Presence of anaemia, Transfusion rates in the first 30 days after surgery. | 30 days after surgery | 
| Smoking | Successful smoking cessation rate, Exhaled CO measured. | At the beginning of study, before and after surgery, at 30 days. | 
| Questionnaires for recovery, anxiety and cardiac risk | Quality of Recovery Score (QoR-15), State-Trait Anxiety Inventory Test (STAI-T), Duke Activity Status Index (DASI) | At the beginning of study, before and after surgery, at 30 days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Comprehensive Complication Index