Preoperative Optimisation of Modifiable Risk Factors in Surgery of the Pancreas (PROMISE-P)

Preoperative Optimisation of Modifiable Risk Factors in Surgery of the Pancreas: the Implementation of Best Practice Before Pancreatic Resection

The goal of this stepped-wedge randomized controlled trial is to investigate whether implementation of a best practice program for preoperative optimisation (prehabilitation program) with a focus on screening, assessment, and intervention of 8 potentially (partly) modifiable risk factors in patients with (suspected) pancreatic cancer will improve outcome. The main questions it will aim to answer are:

1. Does a prehabilitation program improve the time to functional recovery after pancreatic surgery?
2. Does a prehabilitation program lead to a reduction in the Comprehensive Complication Index after pancreatic surgery?

Study Overview

• Status: Recruiting
• Conditions: Postoperative Complications; Surgery; Pancreas Cancer; Prehabilitation
• Intervention / Treatment: Behavioral: Preoperative optimisation program

Detailed Description

Background In the past, little attention has been given in the daily practice to the patient's condition before an operation. Recent studies have shown the benefit of preoperative optimisation programs. However, these studies consisted only of smaller studies and were mainly performed in patients who underwent colorectal surgery. Although promising, unfortunately, strong evidence to support the contribution of prehabilitation to optimize the functional outcome after surgery is still lacking and consequently it is not included in the Dutch basic health insurance package.

Objective To investigate whether implementation of a best practice program for preoperative optimisation of patients with a focus on screening, assessment, and intervention of 8 potentially (partly) modifiable risk factors (low (aerobic) fitness level, malnutrition, low psychological resilience, comorbidities (iron deficiency (anaemia), impaired glucose control and frailty), and intoxications (alcohol and smoking behaviour)) will improve the time to functional recovery.

Study design A nationwide stepped-wedge cluster randomized trial. In this design all participating centres will cross over from current practice to the best practice program, in a randomised order. At the end of the study, all centres will have implemented the best practice program.

Study population 13 centres performing major pancreatic surgery in the Netherlands collaborating within the Dutch Pancreatic Cancer Group (DPCG).

Intervention Preoperative screening of all patients scheduled for pancreatic resection on (aerobic) fitness level, malnutrition risk, psychological resilience, haemoglobin, iron and HbA1c concentration, frailty, and alcohol and smoking behaviour. All patients are provided with a patient-tailored, multimodal prehabilitation program, in which these potentially (partly) modifiable factors are preoperatively addressed. This program is based on findings in previous screening and prehabilitation programs, a national inventory of current preoperative care protocols and expert opinion. Consensus upon this program was reached with pancreatic surgeons from all centres of the DPCG. The final program was critically reviewed by the advisory committee of internationally respected experts in the field of prehabilitation and pancreatology.

Comparison Preoperative care according to current practice.

• Study Type: Interventional
• Enrollment (Estimated): 2575
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marcel den Dulk, MD PhD; Phone Number: +3143 3875492; Email: marcel.den.dulk@mumc.nl
• Study Contact Backup: Name: Heleen Driessens, MD; Phone Number: +316 83058108; Email: h.driessens@umcg.nl

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Recruiting
    • OLVG
    • Contact: Tom Karsten, MD PhD
  • Amsterdam, Netherlands
    • Recruiting
    • Amsterdam University Medical Center
    • Contact: Marc Besselink, MD PhD
  • Breda, Netherlands
    • Recruiting
    • Amphia Hospital
    • Contact: Jennifer Schreinemakers, MD PhD
  • Den Bosch, Netherlands
    • Recruiting
    • Jeroen Bosch Hospital
    • Contact: Koop Bosscha, MD PhD
  • Eindhoven, Netherlands
    • Recruiting
    • Catharina Hospital
    • Contact: Ignace de Hingh, MD PhD
  • Enschede, Netherlands
    • Recruiting
    • Medisch Spectrum Twente
    • Contact: Daan Lips, MD PhD
  • Groningen, Netherlands
    • Recruiting
    • University Medical Center Groningen
    • Contact: Joost Klaase, MD PhD
  • Leeuwarden, Netherlands
    • Recruiting
    • Medisch Centrum Leeuwarden
    • Contact: Eric Manusama, MD PhD
  • Leiden, Netherlands
    • Recruiting
    • Leiden University Medical Center
    • Contact: Sven Mieog, MD PhD
  • Maastricht, Netherlands, 6202AZ
    • Recruiting
    • Maatricht University Medical Center
    • Contact: Marcel den Dulk, MD PhD
  • Nijmegen, Netherlands
    • Recruiting
    • Radboud University Medical Center
    • Contact: Kees van Laarhoven, MD PhD
  • Rotterdam, Netherlands
    • Recruiting
    • Erasmus Medical Center
    • Contact: Bas Groot Koerkamp, MD PhD
  • Utrecht, Netherlands
    • Recruiting
    • RAKU
    • Contact: Hjalmar van Santvoort, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• All patients who are planned for a curative treatment with or without neoadjuvant treatment and elective pancreatic resection in one of the centres of the Dutch Pancreatic Cancer Group (i.e. all centres performing major pancreatic surgery)

Exclusion Criteria:

• age < 18 years
• acute pancreatic resections (resection scheduled within two weeks)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard care; Receiving standard preoperative care
Experimental: Best practice program; Implementation of best practice preoperative optimisation program	Behavioral: Preoperative optimisation program; Preoperative screening of all patients scheduled for pancreatic resection on (aerobic) fitness level, malnutrition risk, psychological resilience, haemoglobin, iron and HbA1c concentration, frailty, and alcohol and smoking behaviour. All patients are provided with a patient-tailored, multimodal prehabilitation program, in which these potentially (partly) modifiable factors are preoperatively addressed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to functional recovery	Functional recovery is achieved when all of the following five criteria are met: a) restored level of mobility at the preoperative level, b) sufficient pain control with oral medication alone, c) ability to maintain at least 50% daily required energy intake, d) no intravenous fluid administration, and e) no clinical signs of infection.	On average 6-10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comprehensive Complication Index (CCI)	The CCI is calculated as the sum of all complications that are weighted for their severity, with a range from 0 to 100, whereby a higher score indicates presence of more complications and/or more severe complications.	30 days postoperative
Length of hospital stay	Length of hospital stay of the primary admission, measured in days	On average 2 weeks postoperative
Readmissions	Readmissions within 30 days after discharge	30 days after discharge of primary admission
Postoperative complications	Any postoperative complication	During primary admission, on average 14 weeks postoperative
Incremental cost-effectiveness ratio (ICER)	The difference in costs between standard care and best practice care divided by the difference in health benefits, measured in quality-adjusted life years (QALYs).	1 year postoperative
Evaluation of health status	Reported health status measured with questionnaire EQ-5D-5L	At baseline, 3 months and 12 months postoperative
Evaluation of quality of life for cancer patients	Reported quality of life measured with questionnaire EORTC QLQ-C30	At baseline, 3 months and 12 months postoperative

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Collaborators: Rising Tide Foundation
• Investigators: Principal Investigator: Marcel den Dulk, MD PhD, Maastricht University Medical Center/ University Maastricht

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2024
• Primary Completion (Estimated): September 2, 2027
• Study Completion (Estimated): September 2, 2028

Study Registration Dates

• First Submitted: April 14, 2023
• First Submitted That Met QC Criteria: May 1, 2023
• First Posted (Actual): May 9, 2023

Study Record Updates

• Last Update Posted (Actual): October 26, 2024
• Last Update Submitted That Met QC Criteria: October 23, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Pancreas; Prehabilitation; Preoperative optimisation
• Additional Relevant MeSH Terms: Endocrine System Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Postoperative Complications
• Other Study ID Numbers: 2023-3607

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All of the individual participant data collected during the trial will be shared, after deidentification upon reasonable request.
• IPD Sharing Time Frame: Beginning 3 months and ending 5 years following article publication
• IPD Sharing Access Criteria: Data will be available upon request. Request should be directed to marcel.den.dulk@mumc.nl.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No