Trial Title:
Prehabilitation in Pancreatic Surgery
NCT ID:
NCT06069297
Condition:
Pancreatic Cancer
Periampullary Cancer
Frailty Syndrome
Malnutrition
Perioperative/Postoperative Complications
Conditions: Official terms:
Pancreatic Neoplasms
Malnutrition
Frailty
Postoperative Complications
Conditions: Keywords:
Prehabilitation
Physical function
Nutritional status
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Enrolled patients will be randomized (ratio 1:1) and allocated either to the intervention
group (Multimodal Prehabilitation) or to the usual care group
Primary purpose:
Prevention
Masking:
Single (Outcomes Assessor)
Masking description:
The trial is designed as a randomized, controlled, assessor-blind trial
Intervention:
Intervention type:
Other
Intervention name:
Multimodal Prehabilitation
Description:
Preoperative multimodal intervention including exercise training, nutritional therapy and
anxiety reducing techniques, aimed at preventing or attenuating surgery-driven functional
decline. A personalized intervention program will be prescribed based on specific
physical, nutritional and psychological conditions recognized during the multimodal
assessment. Patients will follow a two to three-day per week training for 4 weeks.
Exercise modalities will be adapted to personal preference and patient conditions. Based
on dietary habits, medical conditions and nutritional status, a certified nutritionist
will provide a comprehensive diet management program. A food-based intervention with a
balanced macronutrient composition coupled with oral nutritional supplements will be
prescribed to achieve the estimated daily energy and protein requirements. Participants
will be instructed by psychology-trained personnel on how to reduce anxiety.
Arm group label:
Multimodal Prehabilitation
Summary:
In patients with pancreatic cancer, older age, multiple comorbidities, frailty,
malnutrition and poor functional status are common, especially in individuals receiving
neoadjuvant chemotherapy. These characteristics represent potentially modifiable risk
factors for poor postoperative outcomes.
The goal of this clinical randomized controlled trial is to evaluate the extent to which
a four-week multimodal prehabilitation program impacts on postoperative morbidity,
functional and nutritional status and health-related quality of life in patients with
localized pancreatic or periampullary cancer scheduled for curative surgery.
In addition, the impact of prehabilitation on circulating sarcopenia and cancer cachexia
biomarkers in PDAC patients will be explored.
Included patients will be randomized (ratio 1:1) and allocated either to the intervention
group (Multimodal Prehabilitation), which will receive prehabilitation, or to the control
group, which will receive no prehabilitation.
Detailed description:
BACKGROUND:
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, with 5-year survival
around 10%. The combination of surgical resection and chemotherapy represents the most
efficacious therapy to improve prognosis for localized PDAC. Patients with pancreatic
cancer are generally older adults in whom frailty, sarcopenia and/or malnutrition are
common. These features have all been associated with poor postoperative complications and
reduced survival. Therefore, the preoperative period and the time window after the end of
chemotherapy constitute a unique opportunity to condition modifiable risk factors,
improve functional capacity and address deficiencies in physiologic reserves, which might
otherwise preclude surgery or significantly impede recovery.
Prehabilitation is defined as the process of enhancing patients' functional capacity to
enable them to withstand a stressful event. Multimodal prehabilitation, which defines a
program including physical, nutritional, and psychological interventions, has shown the
most promising results in gastrointestinal cancer surgery. However, no high-quality
evidence is currently available for PDAC patients.
STUDY OBJECTIVES:
Primary Aim: to evaluate if a 4-week multimodal structured prehabilitation program
including physical exercise, nutritional and psychological interventions will result in a
clinically significant increase in functional capacity, nutritional status and
patient-reported health-related quality of life before surgery when compared to a usual
care control group, and evaluate the extent to which multimodal prehabilitation impacts
on postoperative morbidity and patient recovery compared to usual care.
Secondary Aim: to analyze whether multimodal prehabilitation may impact on the
concentration and activity of a panel of specific circulating molecules involved in
cancer cachexia and skeletal muscle wasting, chronic inflammation.
STUDY DESIGN:
A randomized controlled trial will be performed in PDAC and periampullary cancer patients
with indication to upfront pancreatic resection or pancreatic resection after completion
of neoadjuvant chemotherapy.
Included patients will be randomized (ratio 1:1) and allocated either to the intervention
group (Multimodal Prehabilitation), which will receive prehabilitation, or to the control
group, which will receive no prehabilitation. All patients will receive the same
intraoperative and postoperative care based on an established enhanced recovery pathway.
Inclusion and exclusion criteria as stated in the eligibility section will be assessed
and patients consented to participate in the study if they fulfill inclusion criteria.
RANDOMIZATION AND BLINDING:
The trial is designed as a randomized, controlled, assessor-blind trial. Participants
will be randomly assigned to either multimodal prehabilitation or no prehabilitation
group with a 1:1 allocation using permuted blocks of random sizes. Randomization will be
stratified by neoadjuvant chemotherapy and tumor location (periampullary or pancreatic
head-neck cancer versus pancreatic body-tail cancer). Allocation concealment will be
ensured as the randomization code will not be released until the patient has been
recruited into the trial, which takes place after all baseline measurements have been
completed and informed consent has been signed.
PREOPERATIVE ASSESSMENT:
All patients will be evaluated at baseline (T0) by:
- Patient medical history including comorbidities, presence of signs or symptoms, and
frailty assessment using Fried's criteria.
- Physical performance tests including functional walking capacity (six-minute walk
test), timed up and go test, gait speed assessment and handgrip strength test.
- Assessment of nutritional status by nutrition history, measurement of anthropometric
parameters, completion of nutritional screening questionnaires (MNA, PG-SGA), and
standard biochemical markers of malnutrition and inflammation including albumin,
prealbumin, total lymphocyte count, and C-reactive protein.
- Body composition measurements assessed using two methods:
- multi-frequency bioelectrical impedance analysis (BIA) providing data on
extracellular and intracellular water as % of total body water, fat mass (FM)
as % of body weight, skeletal muscle mass (SK) as % of fat-free mass (FFM) and
phase angle (PA°), intramuscular fat mass (IMAT), basal metabolic rate (BMR)
energy expenditure and hypotalamic- pituitary- adrenal axis index (HPA);
- CT scan image analysis (using preoperative cancer staging and restaging chest
and abdomen CT scans) performing automated imaging segmentation using Data
Analysis Facilitation Suite (DAFS) by Voronoi Health Analytics, Inc.
(https://www.voronoihealthanalytics.com/).
- Overall activity of the autonomic nervous system and heart rate variability through
photoplethysmography (PPG) stress flow test. This exam allows the study and direct
monitoring of all functions of the autonomic nervous system and the related process
of biofeedback.
- Patient reported outcome questionnaires to measure health related quality of life
and patient engagement. The following questionnaires will be administered
- Patient reported outcome measurement information system (PROMIS)29+2, a
validated questionnaire designed to measure self-reported physical, mental and
social health and wellbeing.
- Duke activity status index (DASI), a brief questionnaire designed to assess
physical function by answering whether they are able to perform 12 listed
activities of various intensity (i.e., ambulation, household tasks and leisure
activities).
- EORTC QLQ C30, a generic core questionnaire that measures health-related
quality of life in patients with any cancer.
- EORTC QLQ PAN-26, the pancreatic cancer module that supplements the EORTC
QLQ-C30.
-
- Medically unexplained symptoms (MUS) questionnaire investigates the
presence of vague symptoms to describe a cluster of manifestations such us
chronic fatigue, sleep or appetite disorders, irritable bowel or
constipation, tone or mood disorders, non-specific pain syndromes which
are sometimes underestimated.
- Patient activation measures (PAM)-13, a 13-item questionnaire measuring
patients' self-reported knowledge, motivation, and skills for self-management.
- Hospital Anxiety and Depression Scale (HADS) questionnaire to measure anxiety
and depression.
- Blood sample analysis of circulating cytokines, chemokines, interferons, colony
stimulating factors, main hormones involved in metabolic homeostasis and cancer
cachexia.
Four weeks after baseline assessment, on the day before surgery (T1), all patients will
repeat all evaluations previously performed at T0.
STUDY INTERVENTION Included patients will be randomized (ratio 1:1) and allocated either
to the intervention group (Multimodal Prehabilitation), which will receive
prehabilitation, or to the control group, which will receive no prehabilitation. Patients
in the control group will be treated according to usual standard of care and will be
given informative material regarding healthy lifestyle and how to best prepare for
surgery.
The intervention will consist of a multimodal prehabilitation, a 4-week long preoperative
intervention including exercise training, nutritional therapy and anxiety reducing
techniques, aimed at preventing or attenuating surgery-driven functional decline as
described in the arms and intervention section.
VISITS AND FOLLOW-UP:
Throughout patient hospital stay, postoperative outcomes including complications, will be
recorded. After discharge, patients will be followed-up as routine care by phone calls
from a nurse navigator.
At 30 days (T2), 60 (T3) and 90 days (T4) after surgery, patient recovery will be
re-evaluated during scheduled outpatient visits. Patients will be assessed for:
- Functional capacity by the 6MWT and other physical performance tests including TUG,
gait speed assessment and handgrip strength test.
- Nutritional status by measurement of anthropometric parameters including body weight
(kg), height (cm), and body mass index (kg/m2)
- Body composition by multi-frequency bioelectrical impedance vector analysis (BIVA)
- Health related quality of life through patient reported outcome questionnaires
STATISTICAL METHODS:
The analysis will be conducted on intention to treat basis. Continuous data will be
presented as medians (interquartile range) or means (standard deviation); categorical
data as absolute values and percentages. Dichotomous data will be compared by two tailed
chi-square test or Fisher's exact test. Continuous measurements will be compared between
groups using the Mann-Whitney U test or T-Student test for normally distributed data.
Baseline characteristics of the two groups will be reported in order to confirm the
adequacy of the randomization process.
CCI will be described as the mean plus the standard deviation (SD) or median plus
interquartile range (IQR), depending on its distribution. To analyze the difference in
terms of CCI between groups t-student Test will be adopted in case of normal
distribution, otherwise Mann-Whitney U test will be used.
6MWT as a functional capacity measure is a continuous variable. This data will be
described as means, plus SD, at each time point. To accommodate the repeat measurements
for individuals, a generalized linear mixed model will be used to compare results from
both arms.
Pre-planned subgroup analysis in patients with higher risk features at enrollment (e.g.,
malnourished, sarcopenic obese, low physical function, frail) will also be performed to
evaluate the effectiveness of prehabilitation in this population. Statistical analysis
will be performed using STATA® version 16 software.
SAMPLE SIZE:
The size of the sample was calculated on the basis of the primary aim of the study: the
reduction of postoperative complications as determined with the CCI score at 90 days
after surgery. In our preliminary data on PDAC surgical population, the mean (SD) CCI is
21.0 (SD 16), and the target reduction is 30%. An alpha of 0.05 and power of 0.80
(two-sided test) was used. Expecting a dropout rate of 10%, 113 patients are needed in
each arm for an overall sample of 226 patients.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Age ≥ 18 years
- Indication for curative resection for pancreatic or periampullary cancer
- Signed Informed consent
Exclusion Criteria:
- Metastatic or unresectable disease found preoperatively
- Comorbidities contraindicating prehabilitation regimen (exercise and nutritional
intervention) such as orthopedic, cognitive disabilities, chronic renal failure
(dialysis or creatinine >250 mmol)
- ASA score 4-5
- Pregnancy
- Illiteracy (inability to read and understand Italian language)
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
San Raffaele Hospital
Address:
City:
Milan
Zip:
20132
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Nicolò Pecorelli, MD
Phone:
+390226432111
Email:
pecorelli.nicolo@hsr.it
Start date:
July 14, 2023
Completion date:
July 13, 2026
Lead sponsor:
Agency:
IRCCS San Raffaele
Agency class:
Other
Collaborator:
Agency:
Ministry of Health, Italy
Agency class:
Other
Source:
IRCCS San Raffaele
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06069297
