Clinical trial NCT03522454: The PERFORM-TAVR Trial
Official title: Protein and Exercise to Reverse Frailty in OlderR Men and Women Undergoing TAVR: The PERFORM-TAVR Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Frail Elderly
Exercise
Dietary Supplements
Postoperative Care
Rehabilitation
Transcatheter Aortic Valve Replacement
Keywords: Frailty
TAVR
Lead sponsor: Jewish General Hospital
Sponsor class: OTHER
Collaborators: name: University of British Columbia
name: McGill University Health Centre/Research Institute of the McGill University Health Centre
name: St. Boniface Hospital
name: Montreal Heart Institute
name: Hamilton Health Sciences Corporation
name: Ottawa Heart Institute Research Corporation
name: Unity Health Toronto
name: Sunnybrook Research Institute
name: Hopital du Sacre-Coeur de Montreal
name: Centre hospitalier de l'Université de Montréal (CHUM)
First posted: 2018-05-11
Enrollment: 200
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The PERFORM-TAVR trial (Protein and Exercise to Reverse Frailty in OldeR Men and women undergoing Transcatheter Aortic Valve Replacement) is a multicenter randomized clinical trial with a parallel-group design. The investigators will screen consecutive patients ≥70 years of age before TAVR and enrol those that have evidence of physical frailty defined by an SPPB score ≤8 or an SF36-PF score ≤55. The investigators will randomly allocate 200 patients to receive a multi-faceted intervention consisting of a home-based exercise program and a protein-rich oral nutritional supplement or usual lifestyle counselling. The primary endpoint will be the change in SF36-PF score at 12 weeks.

Detailed description: STUDY DESIGN:

The PERFORM-TAVR trial (Protein and Exercise to Reverse Frailty in OldeR men and woMen undergoing Transcatheter Aortic Valve Replacement) is a multicenter randomized clinical trial with a parallel-group design. We will screen consecutive patients ≥70 years of age before TAVR and enroll those that have evidence of physical frailty defined as an SPPB score ≤8 or an SF36-PF score ≤55. The SPPB and SF36-PF were chosen as the main inclusion criteria and also as key endpoints based on their ease-of-use, reproducibility, responsiveness to change, and superior predictive value for mortality and patient-centered outcomes in the Frailty-AVR Study. We will randomly allocate 200 patients to receive a multi-faceted intervention consisting of home-based exercise and protein supplementation or standard-of-care lifestyle counselling.

INTERVENTION GROUP:

The multi-faceted intervention consists of two synergistic components performed by participants at their homes. The first component is a home-based supervised exercise program that combines walking and weight-bearing exercises to build strength and balance performed for 12 weeks after the patient is discharged home post-TAVR. The exercises are based on the WEBB program that was developed at the University of Sydney and validated to help therapists individually prescribe progressive exercise that is challenging but safe for older adults (http://www.webb.org.au/attachments/File/WEBB_draft_19.pdf). Starting as soon as the patient returns home post-TAVR, a trained therapist (TT; physiotherapist or certified exercise physiologist, depending on local expertise) will visit their home for 1 hour twice weekly over a 12-week period to supervise and tailor the exercises according to each individual's capability and progress, and to reinforce the goal of moderate-intensity aerobic activity such as brisk walking at least 30 minutes 5 days per week. If the patient is transferred to a convalescence or inpatient rehabilitation facility or another hospital, the TT will defer home visits until they are discharged to their home. If the patient is referred to an outpatient rehabilitation program, the TT will continue to perform home visits concurrently. The low use of center-based rehabilitation reflects well-known accessibility barriers in our Canadian healthcare environment and reaffirms the high relevance of our home-based intervention.

To monitor compliance, the TT will ask patients to note their daily exercises in their log book and wear a wrist-worn accelerometer (Garmin Vivofit 4) to record daily step counts. The accelerometer provides motivational cues such as individualized daily step count goals and gentle beeps to remind patients to move when they have been sedentary for a prolonged period during the day. We previously used the Garmin Vivofit in an elderly cardiac population as part of the Get Going Trial and found it to be "geriatric-friendly" owing to its minimalist interface, large font size, lightweight waterproof design, and year-long battery that does not necessitate charging or computer syncing. The majority of patients (including those ≥80 years) reported a high level of comprehension and satisfaction with this device. The TT will sync the patient's accelerometer devices at every home visit using a smartphone or tablet, review their step counts, and provide personalized coaching to increase daily walking.

The second component is a protein-rich oral nutritional supplement (Ensure Enlive) with 20g protein and 1.5g HMB per serving, delivered as a ready-to-drink beverage in 235 mL bottles, consumed twice daily for 4 weeks pre-TAVR and 12 weeks after the patient is discharged home post-TAVR. This beverage contains 350 calories, and is provided in chocolate and vanilla flavors. It should be consumed with breakfast (first serving of the day) and with exercise (second serving of the day), not before meals, so as to supplement rather than replace food intake. The HMB ingredient stimulates muscle protein synthesis, particularly when combined with exercise due to the muscle priming effect. To monitor and promote compliance, the TT will ask patients to note their beverage consumption in their log book, instruct them to consume a beverage during home exercise sessions, periodically replenish their supply of beverages during home visits, and perform bottle counts. The log book provided to the participants also contains information on healthy eating and maintaining an active lifestyle (same as control group).

LIFESTYLE COUNSELLING GROUP:

Lifestyle counselling consists of formalized usual care - instructing patients to perform moderate-intensity aerobic activity at least 30 minutes 5 days per week as tolerated and eat a balanced diet based on the AHA/ACC Guideline on Lifestyle Management. In order to standardize this counselling and ensure that it is safely carried out in both groups, the TT will provide and explain information on healthy eating and maintaining an active lifestyle based on the "Easy Tips for Heart Healthy Eating" and "Walking for a Healthy Heart" brochures designed by the American Heart Association. The latter outlines practical tips to safely begin a walking program and gradually increase walking time over a 12-week period to meet the goal of 150 minutes per week. All of this information will be easily legible in a log book provided to participants. We will not instruct lifestyle counselling group patients to consume protein-rich nutritional supplements during the trial unless prescribed by their treating physician.

OUTCOME MEASURES:

The primary endpoint is the SF36-PF score at 12 weeks. Secondary endpoints are physical functioning measured by the Short Physical Performance Battery (SPPB), health-related QOL measured by the 36-Item Short Form Health Survey (SF-36), cognitive function measured by the Montreal Cognitive Assessment (MoCA), habitual physical activity level measured by the modified Paffenbarger questionnaire, handgrip strength measured by a Jamar dynamometer, body composition and phase angle measured by a portable bioimpedance device, frailty measured by the Essential Frailty Toolset, sarcopenia measured by the SARC-F questionnaire and EWGSOP criteria, and a composite safety endpoint of all-cause mortality, injurious fall, acute kidney injury, or readmission for worsening angina, heart failure, or arrhythmia. The aforementioned primary and secondary endpoints will be re-assessed at 24 weeks to detect latent effects and sustained adherence, and vital status and questionnaires will be assessed by telephone at 52 weeks. Clinical events will be defined according to the Valve Academic Research Consortium-2 data dictionary. A 3-member independent Data Safety and Monitoring Board will review all adverse events.

Eligibility criteria: Inclusion Criteria:

* Age ≥70 years
* Undergoing TAVR
* Physically frail: SPPB score ≤8 or SF36-PF score ≤ 55 pre-TAVR
* Informed written or verbal consent

Exclusion Criteria:

* Decompensated or non-ambulatory class IV symptoms of angina, dyspnea, claudication
* Uncontrolled diabetes with HbA1C \>8.5% (or mean glucose ≥11.0 in the absence of a HbA1C test)
* Glomerular filtration rate (GFR) \<30 mL/min/1.73 m2 by the MDRD equation
* Cirrhosis
* Allergy to ingredient in beverage
* Inability to safely ingest beverage by mouth
* Inability to walk without human assistance or high-risk of falls
* Moderate-to-severe cognitive impairment
* Significant language barrier
* COVID positive or suspected at screening

Primary outcomes:
measure: SF36-PF
timeFrame: 3 months
Secondary outcomes:
measure: SPPB
timeFrame: 3 and 6 months
measure: Health-related quality of life
timeFrame: 3, 6, and 12 months
measure: Habitual physical activity (in kcal per week)
timeFrame: 3, 6, and 12 months
measure: Frailty
timeFrame: 3 and 6 months
measure: Sarcopenia
timeFrame: 3, 6, and 12 months
measure: Fat free mass (in kg)
timeFrame: 3 and 6 months
measure: Phase angle (in degrees)
timeFrame: 3 and 6 months
measure: Handgrip strength (in kg)
timeFrame: 3 and 6 months
measure: Cognitive function
timeFrame: 3 and 6 months
measure: Number of participants suffering composite safety endpoint
timeFrame: 3 and 6 months
measure: Number of participants suffering death from any cause
timeFrame: 3, 6, and 12 months
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Jewish General Hospital / McGill University Health Centre
state: Quebec
Study officials:
affiliation: Jewish General Hospital
name: Jonathan Afilalo, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: