Multicomponent Prehabilitation and Outcomes in Elderly Patients With Frailty

Sponsor

Peking University First Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04715581

Collaborator

(none)

538

Enrollment

Location

Arms

48.2

Anticipated Duration (Months)

11.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study is designed to investigate the effect of a multicomponent prehabilitation pathway on early and long-term outcomes in elderly patients with frailty recovering from surgery for digestive cancer.

Condition or Disease	Intervention/Treatment	Phase
Old Age; Debility Digestive Cancer Surgery Preoperative Rehabilitation Nutrition Therapy Outcomes	Dietary Supplement: Preoperative nutritional optimization Other: Preoperative exercise training	N/A

Detailed Description

Frailty is an age-related syndrome characterized with diminished physiological reserve that results in decreased homeostatic capacity and increased vulnerability to any stress from minor to major. Approximately 10% to 20% of adults aged 65 years and older present with frailty, and the incidence doubles among those of 85 years and older. Among elderly cancer patients especially those with digestive cancer, the prevalence of frailty and pre-frailty can be as high as 50%. Malnutrition often coexists with frailty, and indeed contribute to the development of frailty. As a matter of fact, the proportion of malnutrition also increases with age even in high-income countries.

Frailty is strongly associated with worsening outcomes in surgical patients, including higher delirium, high non-delirium complications, high perioperative mortality, as well as decreased activity of daily life, cognitive dysfunction and work disability in long-term survivors. Furthermore, malnutrition as a prominent factor in the development of frailty also has adverse impacts on the duration of hospitalization, complications, and survival after surgery. Therefore, it is urgently needed to understand how to enhance the recovery of these patients following surgery.

Exercises and rehabilitation, in combination with nutritional supplement, may reverse or mitigate frailty, promote postoperative recovery, and improve clinical outcomes. However, the reported effectiveness varies with interventions and are not sufficiently robust to guide good clinical practice. The purpose of this study is to investigate the effect of multimodal prehabilitation on early and long-term outcomes in elderly patients with frailty.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

538 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This is a randomized controlled trial.This is a randomized controlled trial.

Masking:

Triple (Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Supportive Care

Official Title:

Effect of Multicomponent Prehabilitation on Early and Long-term Outcomes in Elderly Patients With Frailty After Digestive Surgery for Cancer: A Randomized-controlled Study

Actual Study Start Date :

Nov 25, 2021

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Multicomponent prehabilitation group Patients in the intervention group will receive nutritional optimization and exercise training before the surgery.	Dietary Supplement: Preoperative nutritional optimization Indication for oral nutritional supplementation: Patients at risk of malnutrition (MNA-SF 8-11) or with malnutrition (MNA-SF 0-7). Protocol of nutritional optimization: Enteral nutritional powder (Ensure for patients without diabetes and Glucerna for patients with diabetes) twice a day. The target protein intake is 1.5-1.8 g/kg/d. Patients with iron deficient anemia (hemoglobin <130 g/L for men and <120 g/L for women) will be given oral iron therapy. The duration of nutritional optimization: Two weeks prior to the surgery to one day prior to the surgery. Other: Preoperative exercise training Exercise training includes aerobic exercise and respiratory training. A home-based aerobic exercise will be performed for at least 1-2 times per day. The respiratory training will be performed for at least 2-3 times per day. Every training should be last for 45 minutes to 1 hour. If the patient can not tolerate, the training time should be reduce to 30 minutes. Aerobic exercise includes jogging, walking or climbing stairs. Exercise intensity will be based on patients' tolerance. The goal of the training is to complete the training plan as far as possible. Respiratory training include thoracic breathing exercise and cough training.
No Intervention: Control group Patients in the control group will maintain normal diet and normal activity before surgery.

Arm

Intervention/Treatment

Experimental: Multicomponent prehabilitation group

Patients in the intervention group will receive nutritional optimization and exercise training before the surgery.

Dietary Supplement: Preoperative nutritional optimization

Indication for oral nutritional supplementation: Patients at risk of malnutrition (MNA-SF 8-11) or with malnutrition (MNA-SF 0-7). Protocol of nutritional optimization: Enteral nutritional powder (Ensure for patients without diabetes and Glucerna for patients with diabetes) twice a day. The target protein intake is 1.5-1.8 g/kg/d. Patients with iron deficient anemia (hemoglobin <130 g/L for men and <120 g/L for women) will be given oral iron therapy. The duration of nutritional optimization: Two weeks prior to the surgery to one day prior to the surgery.

Other: Preoperative exercise training

Exercise training includes aerobic exercise and respiratory training. A home-based aerobic exercise will be performed for at least 1-2 times per day. The respiratory training will be performed for at least 2-3 times per day. Every training should be last for 45 minutes to 1 hour. If the patient can not tolerate, the training time should be reduce to 30 minutes. Aerobic exercise includes jogging, walking or climbing stairs. Exercise intensity will be based on patients' tolerance. The goal of the training is to complete the training plan as far as possible. Respiratory training include thoracic breathing exercise and cough training.

No Intervention: Control group

Patients in the control group will maintain normal diet and normal activity before surgery.

Outcome Measures

Primary Outcome Measures

A composite of delirium and non-delirium complications within 7 days after surgery (sub-study). [Up to 7 days after surgery.]
Delirium will be assessed with the 3-Dimensional Confusion Assessment Method. Non-delirium complications are defined as new onset medical events other than delirium that are harmful to patients' recovery and required therapeutic intervention, i.e., grade II or higher on Clavien-Dindo classification.
Recurrence-free survival after surgery. [Up to two years after surgery.]
Events include recurrence, metastasis, or all-cause death, whichever come first.

Secondary Outcome Measures

Intensive care unit admission after surgery (sub-study). [Up to 30 days after surgery.]
Intensive care unit admission after surgery.
Incidence of delirium within 7 days after surgery (sub-study). [Up to 7 days after surgery.]
Delirium will be assessed with the 3-Dimensional Confusion Assessment Method.
Time to oral fluid intake after surgery (sub-study). [Up to 30 days after surgery.]
Time to oral fluid intake after surgery.
Time to oral food intake after surgery (sub-study). [Up to 30 days after surgery.]
Time to oral food intake after surgery.
Time to out-of-bed activity after surgery (sub-study). [Up to 30 days after surgery.]
Time to out-of-bed activity after surgery.
6-minute walk distance at hospital discharge (sub-study). [At hospital discharge, up to 30 days after surgery.]
6-minute walk distance at hospital discharge.
Length of hospital stay after surgery (sub-study). [Up to 30 days after surgery.]
Length of hospital stay after surgery.
Incidence of non-delirium complication within 30 days after surgery (sub-study). [Up to 30 days after surgery.]
Non-delirium complications are defined as new onset medical events other than delirium that are harmful to patients' recovery and required therapeutic intervention, i.e., grade II or higher on Clavien-Dindo classification.
All-cause 30-day mortality after surgery (sub-study). [Up to 30 days after surgery.]
All-cause 30-day mortality after surgery.
Quality of life at 30 days after surgery (sub-study). [At 30 days after surgery.]
Quality of life will be assessed with the World Health Organization Quality of Life brief version (WHOQOL-BREF) which is a 24-item questionnaire that assesses the quality of life in physical, psychological, and social relationship, and environmental domains. The score ranges from 0 to 100 for each domain, with higher score indicating better function.
Cognitive function at 30 days after surgery (sub-study). [At 30 days after surgery.]
Cognitive function will be assessed with the Modified Telephone Interview for Cognitive Status (TICS-m) which is a 12-item questionnaire that verbally assesses global cognitive function via telephone. The score ranges from 0 to 50, with higher score indicating better function.
Sleep quality at 30 days after surgery (sub-study). [At 30 days after surgery.]
Sleep quality will be assessed with the Pittsburgh sleep quality index which is a 9-item questionnaire that assess subjective quality of sleep during the past 1 month. The score ranges from 0 to 21, with higher score indicating poor sleep quality.
Overall survival after surgery. [Up to 2 years after surgery.]
Events include all-cause death.
Cancer specific survival after surgery. [Up to 2 years after surgery.]
Events are cancer-specific death which is defined as death fully attributable to the cancer for which the index surgery is performed and usually involving cancer recurrence and/or metastasis after exclusion of other causes such as stroke and myocardial infarction. Deaths from other causes are censored at the time of death.
Event-free survival after surgery. [Up to 2 years after surgery.]
Events include recurrence/metastasis, new-onset diseases, new-onset tumors, or all-cause mortality, whichever come first.

Other Outcome Measures

Intensity of pain after surgery (sub-study). [Up to 7 days after surgery.]
Intensity of pain will be assessed twice daily with the numeric rating scale which is a 11-point scale where 0=no pain and 10=the worst pain.
Subjective sleep quality after surgery (sub-study). [Up to 7 days after surgery.]
Subjective sleep quality will be assessed daily with the numeric rating scale which is a 11-point scale where 0=the best sleep and 10=the worst sleep.
Sleep architecture during the night of surgery (sub-study, part of enrolled patients). [During the night of surgery.]
Sleep will be evaluated with the polysomnographic monitoring during the night of surgery.
Quality of life at 1 year after surgery. [At 1 year after surgery.]
Quality of life will be assessed with the World Health Organization Quality of Life brief version (WHOQOL-BREF) which is a 24-item questionnaire that assesses the quality of life in physical, psychological, and social relationship, and environmental domains. The score ranges from 0 to 100 for each domain, with higher score indicating better function.
Cognitive function at 1 year after surgery. [At 1 year after surgery.]
Cognitive function will be assessed with the Modified Telephone Interview for Cognitive Status (TICS-m) which is a 12-item questionnaire that verbally assesses global cognitive function via telephone. The score ranges from 0 to 50, with higher score indicating better function.

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years to 89 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

Age ≥65 years but <90 years;
Scheduled to undergo major surgery for digestive cancer with an expected duration of 2 hours and longer, including cancers of esophagus, stomach, small intestine, colon, rectum, pancreas, liver, and biliary tract;
Clinical Frailty Scale ≥5;
Provide written informed consent.

Exclusion Criteria:

Preoperative history of schizophrenia, epilepsy, Parkinsonism, or myasthenia gravis;
Inability to communicate due to coma, profound dementia, or language barrier;
Inability to participate in preoperative rehabilitation due to paralysis, fracture or other movement disorder;
Inability to take oral diet due to preoperative gastrointestinal disease or other disease;
Severe heart dysfunction (left ventricular ejection fraction <30% or New York Heart Association classification IV), severe hepatic dysfunction (Child-Pugh class C), severe renal dysfunction (undergoing dialysis before surgery), or American Society of Anesthesiologists classification of grade 4 or higher;
Other reasons that are considered unsuitable for study participation.