Administrative information
Title {1} | CANOPTIPHYS study protocol: Optimising PHYSical function before CANcer surgery: effects on complications and quality of life after gastrointestinal cancer surgery in older people at risk. A multicentre, randomised, parallel-group superiority study. |
Trial registration {2a and 2b}. | 2a: ClinicalTrials.gov Identifier: NCT04878185 2b: Se Item 2a. |
Protocol version {3} | May 7, 2021, version 1. |
Funding {4} | Financial support for the study is provided through grants from the non-profit organisations The Swedish Cancer Society (period for support: 2020-2023) and The Swedish Research Council (period for support: 2020-2023). Both organisations provide support through grants aimed at salary expenses (data collection personnel at recruitment sites, doctoral- and postdoctoral positions) and costs related to material (lab equipment). None of the funding organisations has any vested interest in the outcome of the study. Financial support was also provided through The Erling-Persson Foundation (a framework funding grant to AT, Grant # 140604). |
Author details {5a} | MA, JD: Department of Neurobiology, Care Sciences and Society, Division of Physiotherapy, Karolinska Institutet, Stockholm, Sweden. ME: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Pelvic Cancer, Colorectal Surgery Unit, Karolinska University Hospital, Stockholm, Sweden AT: Department of Clinical Sciences at Danderyds Hospital, Karolinska Institutet & Department of Surgery, Ersta Hospital, Stockholm, Sweden CS: Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. MS: Department of Clinical Sciences at Danderyds Hospital, Karolinska Institutet & Department of Surgery, Ersta Hospital, Stockholm, Sweden MN-B: Department of Neurobiology, Care Sciences and Society, Division of Physiotherapy, Karolinska Institutet, Stockholm, Sweden; Theme Women’s Health and Allied Health Professionals, Medical Unit Occupational Therapy & Physiotherapy, Karolinska University Hospital, Stockholm, Sweden. ER: Department of Neurobiology, Care Sciences and Society, Division of Physiotherapy, Karolinska Institutet, Stockholm, Sweden; Theme Women’s Health and Allied Health Professionals, Medical Unit Occupational Therapy & Physiotherapy, Karolinska University Hospital, Stockholm, Sweden; Stockholm Region Council, FOU nu, Research and Development Unit for the Elderly, Järfälla, Sweden. |
Name and contact information for the trial sponsor {5b} | Karolinska Institutet, 171 77 Stockholm |
Role of sponsor {5c} | Study sponsors and funding parties will have no role in or authority over any aspect of the design, collection, management, analysis, and interpretation of data; writing of the report; and decisions regarding the publication process. |
Introduction
Background and rationale {6a}
Objectives {7}
Primary objectives
Secondary objectives
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Change in physical function (lower extremity functional strength, inspiratory muscle strength, walking distance) at the end of the pre-operative period and at discharge
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Length of stay and destination of discharge
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Self-reported symptoms (patient-reported recovery) at discharge
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Long-term effects (6 months and 1 year post-surgery) on health-related quality of life, physical activity, activities of daily living, and patient-reported recovery.
Trial design {8}
Methods: participants, interventions, and outcomes
Study setting {9}
Eligibility criteria {10}
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Awaiting surgery due to suspicion of colorectal cancer or colorectal liver metastases
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Age 65 years or older
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Maximal walking speed below 2 m/s
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Residential address in Stockholm County
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Understand and speak the Swedish language
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Surgical procedures which hinder post-operative measurements (for instance, hyperthermic intraperitoneal chemotherapy, abdominoperineal rectal resection with musculocutaneous flap)
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If time to surgery < 14 days and postponing the operation for additional 7–14 days constitutes a medical risk (as assessed by the patient’s clinicians)
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Organisational readiness for participation (availability of vital staff: PTs, nurses, doctors)
Who will take informed consent? {26a}
Additional consent provisions for collection and use of participant data and biological specimens {26b}
Interventions
Explanation for the choice of comparators {6b}
Intervention description {11a}
Unsupervised exercise sessions
Criteria for discontinuing or modifying allocated interventions {11b}
Strategies to improve adherence to interventions {11c}
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An exercise protocol filled out by the PT during each supervised session with information regarding the type, duration, and/or number of repetitions performed and achieved intensity for each exercise block. Furthermore, when sufficient intensity is not achieved, the PT is asked to state the reason for this (e.g. pain or fatigue).
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A calendar filled out by the participant for each unsupervised session containing the same information as stated above.
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Automatically stored information regarding number of sessions of IMT performed which will be transferred from the IMT device to a protocol.
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The ActivPAL activity monitor will measure the level of physical activity.
Relevant concomitant care permitted or prohibited during the trial {11d}
Provisions for post-trial care {30}
Outcomes {12}
Primary outcomes
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Pre-operative outcome: change in maximal walking distance
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Post-operative outcome: complications 30 days post-surgery
Secondary outcomes
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The Comprehensive Complication Index (CCI) [36] will be used to further describe the combined burden of PCs. The CCI is based on the CD complication and integrates information from both the number of complications and their severity and can be calculated using a freely available online calculator (https://www.assessurgery.com). The resulting metric is a continuous score ranging from 0 (no burden of complications) to 100 (death from complications). A difference of 10 points has been proposed as MID and to correspond to a 1-grade difference in the CD classification [36].
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Length of hospital stay
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Quality of life
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Destination of discharge from the hospital
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Patient-reported symptoms
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Delirium
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Change in lower extremity strength
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Change in maximal inspiratory muscle strength
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Level of independence in daily living
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Physical activity level
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Mortality
Baseline variables and other outcomes
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Anthropometrics
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Education level
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Comorbidities
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Current medications
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Smoking and alcohol habits
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Nutritional status and risk of malnutrition
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Cognitive impairment
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Patient-centred goals of exercises
Participant timeline {13}
Sample size {14}
Power calculation for 6MWT
Power calculation for CD-classification
Recruitment {15}
Assignment of interventions: allocation
Sequence generation {16a}
Concealment mechanism {16b}
Implementation {16c}
Assignment of interventions: blinding
Who will be blinded {17a}
Procedure for unblinding if needed {17b}
Data collection and management
Plans for assessment and collection of outcomes {18a}
Training of assessors
Plans to promote participant retention and complete follow-up {18b}
Data management {19}
Confidentiality {27}
Plans for collection, laboratory evaluation, and storage of biological specimens for genetic or molecular analysis in this trial/future use {33}
Statistical methods
Statistical methods for primary and secondary outcomes {20a}
Interim analyses {21b}
Methods for additional analyses (e.g. subgroup analyses) {20b}
Methods in analysis to handle protocol non-adherence and any statistical methods to handle missing data {20c}
Plans to give access to the full protocol, participant-level data, and statistical code {31c}
Oversight and monitoring
Composition of the coordinating Centre and trial steering committee {5d}
Principal investigator assumes the following role and responsibilities
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Design and conduct of CANOPTIPHYS
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Preparations of protocols and revisions
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Organising meetings between Trial Management Group (TMG) and lead investigators
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Publication of study reports