PROTein to Enhance outComes of (Pre)Frail paTients Undergoing Cardiac Surgery (PROTECT-CS)

PROTein to Enhance outComes of (Pre)Frail paTients Undergoing Cardiac Surgery - The PROTECT-CS Study

Heart disease in an aging population has resulted in heart surgery being offered to older and more frail patients. Frail patients which make up more than 50% of patients currently undergoing heart surgery are vulnerable to having long-recovery times after surgery, greater loss of independence (i.e. being admitted to a nursing home), experience more depression and anxiety, and have a worse quality of life. In fact, nearly 10% of frail, older adult patients die within 30 days after their heart surgery. The Investigators previous study found that weight-loss and poor muscle strength (i.e. weakness) of frail patients can lead to a worse recovery after heart surgery. Furthermore, inadequate nutrition (aka. malnutrition which is defined as an unintentional, nutritional intake imbalance (not necessarily a decreased intake) before an operation can lead to a vicious cycle of muscle loss causing more frailty, a desire to eat less leading to more muscle loss and increased frailty. At present there is no process to address this important issue in older adults undergoing heart surgery. The Investigators propose to study a practical, real-world, treatment plan that focuses on good nutrition to prevent muscle loss and reduced frailty in vulnerable heart surgery patients.

Study Overview

• Status: Recruiting
• Conditions: Nutrition Poor; Cardiovascular Morbidity; Frail Older Adult Syndrome
• Intervention / Treatment: Dietary supplement: ISOlution protein supplement; Dietary supplement: Placebo Supplement

Detailed Description

To enhance recovery in vulnerable older adults (aged 60 years or older) undergoing major heart surgery. The Investigators seek to reduce the stress of heart surgery on the body by providing muscle-building nutrition supplements (with leucine-rich proteins) at key time-points during the patients' journey.

Objectives of this study:

1. Will leucine-rich protein nutrition supplementation (given in a liquid form like a protein shake) can reduce functional decline in frail older patients undergoing major heart surgery. The Investigators predict that these supplements will lead to a reduction in functional muscle loss (for example how quickly some can walk) and quicker recovery both in hospital and after going home.
2. Will leucine-rich protein nutrition supplementation will enhance health-related quality of life of frail older adult patients after heart surgery. The Investigators predict that patients will be able to return to activities that they enjoy more quickly and experience less depression and anxiety.

In a two-centre clinical trial, frail older adults (patients who are at risk of a long recovery) undergoing major heart surgeries will receive nutrition supplements up to 2 weeks prior to surgery, during post-op recovery in hospital, and for the 8 weeks following hospital discharge. Prior to surgery, all patient in the study will consume a carbohydrate supplement in order to help with nausea symptoms post surgery, glycemic control and GI function. The Investigators will ask 150 (pre)frail patients before their heart surgery to participate. Patient who are 60 years of age or older who agree to be in the study will be randomly selected (75 patients in each group) to receive the nutrition protein shakes or a placebo (a shake without the special protein). In addition to how long a patient needs to stay in hospital after their heart surgery, The Investigators will measure levels of frailty (by different tests of muscle strength), overall nutrition, health related quality of life after surgery as well as mood and anxiety at 2 and 6 months after hospital discharge.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rakesh Arora, BKin,MD,PhD,; Phone Number: 204-258-1078; Email: rarora@sbgh.mb.ca
• Study Contact Backup: Name: David Kent, BKin, MSc; Phone Number: 204-237-2985; Email: dkent@sbgh.mb.ca

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H2A6
      • Recruiting
      • St. Boniface General Hospital
      • Contact: Rakesh Arora, MD,PhD; Phone Number: (204) 258-1078; Email: rarora@sbgh.mb.ca
      • Contact: David Kent, MSc; Phone Number: 204-237-2985; Email: dkent@sbgh.mb.ca
      • Principal Investigator: Rakesh C Arora, MD, PhD
      • Sub-Investigator: Todd A Duhamel, PhD
      • Sub-Investigator: Navdeep Tangri, MD
      • Sub-Investigator: Cornelia Van Ineveld, MD
      • Sub-Investigator: Annette Schultz, PhD
      • Sub-Investigator: Anna Chudyk, PhD
      • Sub-Investigator: Dustin S Kehler, PhD
  • Quebec
    • Montréal, Quebec, Canada, H3T 1E2
      • Not yet recruiting
      • Jewish General Hospital
      • Contact: Jonathan Afilalo, MD; Phone Number: (514) 340-8232; Email: jonathan.afilalo@mcgill.ca
      • Contact: Sarah Lantagne, MSc; Phone Number: 28692 (514) 340-8222; Email: Sarah.Lantagne@ladydavis.ca
      • Principal Investigator: Jonathan Afilalo, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients aged 60 years of age or older, undergoing elective isolated CABG, aortic valve repair or replacement for moderate aortic stenosis or severe regurgitation, mitral valve repair or replacement for moderate stenosis or severe regurgitation or combined CABG/valve procedures.
2. Patients with a Clinical Frailty Score (CFS) from 3 (Managing Well) to 7 (severely frail),
3. Patients with a Short Physical Performance Battery (SPPB) score of 9 or less, or an SF-36 (PF) score of <= 60
4. Patients with an estimated wait time for elective cardiac surgery of 1 week or longer
5. Inpatients with an estimated wait time for non-emergent cardiac surgery of 2 days or longer from hospital admission

Exclusion Criteria:

1. Decompensated or non-ambulatory class IV symptoms of angina, dyspnea, claudication
2. Patients with a Clinical Frailty Score (CFS) of 7 or greater (Severely frail to terminally ill); this will exclude less than 1% of the population on the elective cardiac surgery waitlist.
3. Creatinine clearance <30 mL/min/1.83 m2
4. Cirrhosis (Child-Pugh Class B or greater)
5. Allergy to milk proteins or other ingredients in the supplement
6. Inability to safely ingest beverage by mouth
7. Significant cognitive impairment (MoCA Score < 16)
8. An inability to speak/read in English or French
9. Non-emergent or emergent surgery less than 2 days from hospital admission

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Protein Supplementation; The intended intervention consists of a leucine-rich protein-caloric supplement provided by the Enhanced Medical Nutrition®. The product contains 25 g protein and 3 g Leucine per serving (total caloric value: 160 Kcal.) to be re-constituted and consumed twice daily for a minimum of 2 weeks pre-procedure, twice daily during post-operative recovery and 2 times daily for 8 weeks after the patient is discharged home (Appendix A).	Dietary supplement: ISOlution protein supplement; EXPERIMENTAL ARM: Protein supplement to be re-constituted and consumed twice daily for a minimum of 2 weeks pre-procedure, twice daily during post-operative recovery and 2 times daily for 8 weeks after the patient is discharged home.
Placebo Comparator: Placebo Supplementation; Enrolled patients allocated to the control group will receive the same supplementation schedule as well as compliance verification; however, they will receive a placebo product with no supplemented protein (no nutritional benefit).	Dietary supplement: Placebo Supplement; PLACEBO COMPARATOR ARM: Placebo supplement to be re-constituted and consumed twice daily for a minimum of 2 weeks pre-procedure, twice daily during post-operative recovery and 2 times daily for 8 weeks after the patient is discharged home

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Short-Form 36 physical Function (PF) score	The SF-36 PF assessment captures the physical functioning of participants. It has been moderately correlated with the SPPB and can be used interchangeably if the SPPB is not able to be completed by a patient	Assessed at: baseline, Day of Discharge from Hospital after cardiac surgery, 2 months post surgery and 6 months post surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
health-related QOL measured by the EQ-5D-3L	The EQ-5D-3L measure health related quality of life in our patient cohort	Assessed at: baseline, 2 months post surgery and 6 months post surgery
health-related QOL measured by the EQ-VAS	EQ-VAS measure health related quality of life in our patient cohort	Assessed at: baseline, 2 months post surgery and 6 months post surgery
Depression	measured by the patient health questionnaire (PHQ-9) this assessment measures the symptoms related to depression	Assessed at: baseline, 2 months post surgery and 6 months post surgery
Anxiety	measured by the cardiac anxiety questionnaire (CAQ) this assessment measures the anxiety experienced by patients with cardiovascular disease	Assessed at: baseline, 2 months post surgery and 6 months post surgery
Nutrition assessment	Nutrition is measured by the mini nutritional assessment tool	Assessed at: baseline, Day of Discharge from Hospital after cardiac surgery, 2 months post surgery and 6 months post surgery
Physical Activity Accumulation	This is measured with the use of physical activity monitors call accelerometers. This will be worn for a period of 7 days after each research appointment	Assessed at: baseline, 2 months post surgery and 6 months post surgery
Composite safety endpoint of all-cause mortality, injurious fall, acute kidney injury, or readmission for related events	These parameters will be taken from medical chart reviews post cardiac surgery	Parameters collected at the 2 month time point
Health related QOL as measured by OARS - ADL Scale	This scale measures activities of daily living	Assessed at: baseline, 2 months post surgery and 6 months post surgery
Nausea and vomiting questionnaire	This scale measures symptoms of nausea and vomiting while a patient is recovering in-hospital following cardiac surgery	Assessed (only 1 time point) while patient is in-hospital recovering from cardiac surgery. (i.e. 6 days after cardiac surgery)
Frailty	This measure will be assessed using the Modified Fried Criteria. this includes measures such as: Hand grip strength, exhaustion, nutrition, and physical activity accumulation. This assessment will return a value from 0-5 identifying the frailty of the patient at each of the time points identified	Assessed at: baseline, 2 months post-surgery and 6 months post-surgery

Collaborators and Investigators

• Sponsor: St. Boniface Hospital
• Collaborators: Heart and Stroke Foundation of Canada
• Investigators: Principal Investigator: Rakesh Arora, BKin,MD,PhD, University of Manitoba

Publications and helpful links

General Publications

• Rose AV, Duhamel T, Hyde C, Kent DE, Afilalo J, Schultz ASH, Chudyk A, Kehler DS, Dave M, Arora RC. Randomised controlled trial protocol for the PROTECT-CS Study: PROTein to Enhance outComes of (pre)frail paTients undergoing Cardiac Surgery. BMJ Open. 2021 Jan 29;11(1):e037240. doi: 10.1136/bmjopen-2020-037240.

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2020
• Primary Completion (Estimated): December 30, 2024
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: July 24, 2019
• First Submitted That Met QC Criteria: July 26, 2019
• First Posted (Actual): July 30, 2019

Study Record Updates

• Last Update Posted (Actual): December 18, 2023
• Last Update Submitted That Met QC Criteria: December 15, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Cardiac Surgery; Protein supplementation; Pre-Frail and Frail older adults
• Additional Relevant MeSH Terms: Nutrition Disorders; Malnutrition
• Other Study ID Numbers: G-19-0024269

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No