Compliance With ERAS Protocol in Pancreatic Surgery, Stress Response and Outcomes

Pancreas Cancer Clinical Trial

Official title:

Enhanced Recovery Program, Patient Reported Outcomes, Surgery-specific Outcomes and Stress Response After Pancreatic Surgery: A Prospective Observational Cohort Study by the Thessalic Pancreas Study Group (ThePANas).

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05518643
• Other study ID #: 270
• Secondary ID: 3147
• Status: Recruiting
• Start date: July 15, 2022
• Est. completion date: August 2026

Study information

• Verified date: November 2023
• Source: University of Thessaly
• Contact: Despoina Liotiri, Consultant
• Phone: 00306947941422
• Email: deppieliotiri[@]gmail.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The purpose of this study is to evaluate the impact of compliance with enhanced recovery after surgery (ERAS) program on patient reported outcomes (PROs), surgery-specific outcomes and stress response after pancreatic surgery.

This prospective observational study will include all consecutive patients undergoing pancreatic surgery over a period of three years (2022 - 2025) at two sites, namely University General Hospital of Larissa and IASO Thessalias, in Greece. Patients will be prospectively enrolled after written informed consent. Data will be collected on patient characteristics, surgical and anaesthetic techniques, complications, and length of stay. Quality of life questionnaires will be administered to patients preoperatively, on the fith postoperative day, first follow-up after discharge, one month and six months after the operation. The stress response will be assessed by measuring the Neutrophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio (NLR and PLR) preoperatively, and on the first five postoperative days. Data will be collected on pancreatic surgery-specific complications such as delayed gastric emptying (DGE), post-pancreatectomy haemorrhage (PPH) and postoperative pancreatic fistula (POPF) formation. Anonymised data will be uploaded by the principal investigator on a protected excel spreadsheet for analysis.

Description:

In this study the ERAS program is applied to patients undergoing pancreatic surgery.This is a prospective observational cohort study.The study will take place in two hospitals, the University General Hospital of Larissa (academic center), and IASO Thessalias (largest private general hospital in Thessaly). The study period is three years between May 2022 and April 2025. All patients undergoing pancreatic surgery during this period will be invited to participate in the study. Recruitment will take place at the first appointment with the surgeon when the patient is listed for surgery. The patient will be provided with detailed information about the program which also includes an information leaflet. A written consent form will be signed by patients willing to participate in the study.

Enrolled patients will follow the ERAS pathway for pancreatic surgery during the preoperative, intraoperative, and postoperative period. The ERAS protocol is based on ERAS society recommendations for enhanced recovery after pancreatoduodenectomy.

The ERAS protocol consists of the following items:

First appointment preoperative:

• Patient education about the program

• Prehabilitation with advice on physical exercise and nutritional support

• Advice to stop smoking and alcohol consumption

• Plan for optimisation of comorbidities

• Completion of quality of life questionnaire

Day before surgery:

• Discussion about the program to address any patient concerns and anxieties

• Light meal and carbohydrate drink before bedtime

• Anti-clotting injection 12 hours before surgery

Day of surgery:

• Carbohydrate drink and painkillers 3 hours before surgery

• Clear fluids allowed up to 3 hours before surgery

• Antibiotics within 1 hour before surgical incision

Intraoperative

• Epidural catheter is sited before general anaesthesia

• Multimodal and opioid-sparing analgesia

• Nausea and vomiting prophylaxis

• Goal directed fluid therapy

• Active warming to avoid hypothermia

• Monitoring of blood glucose to maintain normoglycaemia

• Bile culture

• Repeat antibiotics if surgery lasts more than 4 hours

Postoperative:

• Removal of nasogastric tube by postoperative day 1

• Removal of drains by postoperative day 3

• Multimodal analgesia, epidural catheter for 3 days, minimisation of opioids

• Early and scheduled mobilisation and respiratory physiotherapy protocol

• Diet protocol with nutritional drinks and gradual progression from light to solid diet by postoperative day 5

• Removal of urinary catheter when patients able to mobilise on their own, by postoperative day 5

• Cessation of intravenous fluids when patients able to drink 1.5 liters of water, by postoperative day 5

• Regular gastrokinetic medication and gum chewing

• Glycaemic control protocol

• Cessation of antibiotics if bile culture negative and no other indication to continue

The study group will use a checklist with ERAS criteria to follow for each patient and data will be collected on adherence rates to these criteria.

Data will be collected on patient demographics such as sex, age, Body Mass Index (BMI), American Society of Anaesthesiologists (ASA) physical status, and co-morbidities. Data will also be collected on surgical approach and technique, and tumour stage (pTNM). Data will be collected on complications including cardiovascular and respiratory complications, infectious complications (surgical site infection, chest infection, urinary tract infection, intra-abdominal abscess, sepsis), anaesthetic complications (severe pain, delirium, cognitive decline), functional complications (functional decline, new mobility aid use, pressure ulcer, discharge to nursing or rehabilitation facility), renal failure, ileus, return to theatre, readmission, and death. Data will be collected on length of stay and pancreatic surgery-specific complications such as DGE, PPH and POPF formation. International consensus guidelines will be used for definition and grading of these complications.

Quality of life will be assessed by Patient Reported Outcome Measures (PROMS). The stress response will be assessed by measuring NLR and PLR. After anonymization, all data will be prospectively uploaded by local investigators on a protected database and incorporated into a spreadsheet for data analysis.

The data will be analyzed using PROMs, NLR and PLR ratios, postoperative complications, length of hospital stay and cancer recurrence rates as the main outcome variables.The influence of the following factors will be assessed: age, BMI, sex, surgical technique, pTNM stage, preoperative comorbidity, ASA classification, previous SARS-CoV-2 infection, and compliance to the ERAS protocol (<50%, 50-70%, 70-90%, >90%). Adherence will be calculated as the number of interventions fulfilled/20 (total number of preoperative and perioperative interventions).

The statistical model will be multivariate regression analysis. Sample size guidelines for observational studies with regression analysis are based on simulation studies and suggest that the minimum number of events per variable (EPV) should be 10. According to these guidelines the minimum sample size is calculated at 90. To account for 25% loss to follow-up the investigators aim for a total enrollment goal of 120 participants. IBM® SPSS 26 software will be used for statistical analysis. Continuous variables will be compared with One-Way ANOVA or Student's t test for parametric data and with a non-parametric test (Mann-Whitney U test or Kruskal-Wallis test), as indicated. Categorical data will be analysed by using the chi squared or Fisher's exact test where indicated. Quantitative values will be expressed as mean ± standard deviation (SD), median and range, categorical data with percentage frequencies. The odds ratio (OR) will be presented followed by 95% confidence interval (95% CI). Differences in survival and complications between different degrees of compliance will be assessed by the application of log rank test. P < 0.05 will be considered statistically significant.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: August 2026
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• all pancreatic surgery patients

• above the age of 18

• fluent greek speakers

• without communication barriers

Exclusion Criteria:

• younger than 18 years-old

• unable or unwilling to participate

• other surgical procedures

• communication barriers

• lost to follow-up

Related Conditions & MeSH terms

• Delayed Gastric Emptying
• ERAS
• Fistula
• Gastroparesis
• Hemorrhage
• Pancreas Cancer
• Pancreas; Fistula
• Pancreatic Fistula
• Pancreatic Hemorrhage
• Pancreatic Neoplasms
• PROMs

Intervention

Procedure:
• ERAS protocol
ERAS protocol as described above

Locations

Country	Name	City	State
Greece	University of Thessaly	Larissa

Sponsors (3)

Lead Sponsor	Collaborator
University of Thessaly	IASO Thessalias, Larissa University Hospital

Country where clinical trial is conducted

Greece, 

References & Publications (5)

Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993 Mar 3;85(5):365-76. doi: 10.1093/jnci/85.5.365. — View Citation

Austin PC, Steyerberg EW. Events per variable (EPV) and the relative performance of different strategies for estimating the out-of-sample validity of logistic regression models. Stat Methods Med Res. 2017 Apr;26(2):796-808. doi: 10.1177/0962280214558972. Epub 2014 Nov 19. — View Citation

Bujang MA, Sa'at N, Sidik TMITAB, Joo LC. Sample Size Guidelines for Logistic Regression from Observational Studies with Large Population: Emphasis on the Accuracy Between Statistics and Parameters Based on Real Life Clinical Data. Malays J Med Sci. 2018 Jul;25(4):122-130. doi: 10.21315/mjms2018.25.4.12. Epub 2018 Aug 30. — View Citation

Melloul E, Lassen K, Roulin D, Grass F, Perinel J, Adham M, Wellge EB, Kunzler F, Besselink MG, Asbun H, Scott MJ, Dejong CHC, Vrochides D, Aloia T, Izbicki JR, Demartines N. Guidelines for Perioperative Care for Pancreatoduodenectomy: Enhanced Recovery After Surgery (ERAS) Recommendations 2019. World J Surg. 2020 Jul;44(7):2056-2084. doi: 10.1007/s00268-020-05462-w. — View Citation

Spolverato G, Maqsood H, Kim Y, Margonis G, Luo T, Ejaz A, Pawlik TM. Neutrophil-lymphocyte and platelet-lymphocyte ratio in patients after resection for hepato-pancreatico-biliary malignancies. J Surg Oncol. 2015 Jun;111(7):868-74. doi: 10.1002/jso.23900. Epub 2015 Apr 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in patient-reported outcomes as measured by the Health Questionnaire EORTC QLQ-C30	This questionnaire assesses health related quality of life (HRQoL) for cancer patients and includes 30 questions. The QLQ-C30 includes five functional scales (physical, role, emotional, cognitive, and social functioning); eight symptom scales or single items (fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, and diarrhea); an item to assess financial difficulties; 1 global health status scale; and 1 global quality of life scale. Each one of the first 28 items has 4 levels: 1 = not at all, 2 = a little, 3 = quite a bit, 4 = very much. The last 2 questions ask the patient to rate their own health and quality of life on a scale from 1 (very poor) to 7 (excellent). PROMs questionnaires will be distributed in paper format and filled out by pen.	1 week to 1 day before the operation, postoperative day 5, first follow-up 1 week post discharge, 1 month, and 6 months after the operation
Primary	Change on the stress response to surgery measured by the Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratio (NLR and PLR).	NLR and PLR will be calculated by blood tests	1 week to 1 day before the operation, and postoperative days 1-5
Primary	Rate of Delayed Gastric Emptying (DGE)	Number of DGE defined and graded according to the International Study Group of Pancreatic Surgery (ISGPS).	within 6 weeks from operation
Primary	Rate of Post Pancreatic Fistula (POPF) formation	Number of POPF defined and graded according to the International Study Group of Pancreatic Fistula (ISGPF).	within 6 weeks from operation
Primary	Rate of Postoperative Pancreatic Haemorrhage (PPH)	Number of PPH defined and graded according to the International Study Group of Pancreatic Surgery (ISGPS).	within 6 weeks from operation
Secondary	Length of hospital stay (LOS)	Total number of days spent in the hospital (including any readmission)	within 6 weeks from operation
Secondary	Overall morbidity rate	Number of any perioperative adverse events graded according to Clavien-Dindo	Within 3 months from operation
Secondary	Cancer recurrence rate	Number of patients with cancer recurrence with metastases	within 1 year from operation