Clinical trial NCT04088838: Natural Course of Pain Following Surgery Through an Abdominal Incision
Official title: Natural Course of Pain Following Surgery Through an Abdominal Incision: The Role of Adhesions and Other Factors in Chronification of Abdominal Pain
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Adhesions Abdominal
Adhesions Pelvic
Surgery Induced Tissue Adhesions
Chronic Pain
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2019-09-13
Enrollment: 650
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with undergoing different types of abdominal surgery (laparotomy and laparoscopy). Included are all patients undergoing elective surgery. Patients undergoing laparoscopic cholecystectomy and caesarean section are excluded because both are very frequent procedures with a low risk of chronic post-operative pain and low risk of adhesions. These procedure could therefore significantly impact the power of the study. Although patients after laparoscopic cholecystectomy frequently report pain, these pain symptoms are often attributable to persistence of pre-existing pain. There are known difficulties in differential diagnosis of symptomatic cholelithiasis and dyspepsia, that might interfere with indication for cholecystectomy

Brief summary: Chronic abdominal pain is highly prevalent in patients undergoing abdominal surgery. Adhesions are reported to be one of the most common causes of chronic pain after surgery. There is little epidemiological data on the natural course and risk factors of pain. In this study the investigators will assess risk factors for chronic pain and natural course by tracking pain scores through an app in a cohort of 1,500 patients undergoing abdominal surgery. In part two of the study patients with persistent abdominal pain at 12 months, that meet IASP criteria for chronic pain will have clinical investigations to determine the cause of their pain. This investigation includes cineMRI for diagnosis and mapping of adhesions.

Detailed description: Rationale: Chronic abdominal and pelvic pain are highly prevalent in among patients who had abdominal surgery in history. An estimate of 11-20% of all patients undergoing different kinds of abdominal surgery will develop chronic abdominal pain. Adhesions (a form of internal scar tissue) are the most common pathology found in patients undergoing diagnostic laparoscopy for pain. Other factors that might be associated with chronic post-operative pain are anxiety, depression, and female sex. Little is known about the natural course of pain after abdominal surgery, risk factors for developing chronic pain, and the mechanisms causing pain in patients with adhesions. In this longitudinal study the investigators will prospectively study the natural course of pain through repeated measurements, and predictive factors for chronification of pain after different types of abdominal surgery.

Objective: In Phase 1 the investigators will study the natural course of pain following abdominal surgery. Primary objective for phase 1 is to assess risk factors for chronic pain at 12 months after surgery; where chronic pain is defined as daily continues or intermittent pain with maximal pain scores of 4 or higher during more than 3 months in accordance to IASP criteria. As a pivotal secondary outcome we will describe and model the duration (days) of moderate (worst pain score 4 to 6) to severe pain (worst pain score 7 or higher), and assess factors that impact the chance in painscore using mixed models. In phase two the investigators will assess the impact of adhesions on chronic pain. Primary objective for phase two is to compare incidence and extent of adhesions on cineMRI between patients who developed chronic pain and patients who did not develop chronic pain at 12 months after surgery.

Study design: This is prospective cohort study, including 1,500 patients scheduled for elective abdominal surgery. In phase one, patients are asked to fill a comprehensive questionnaire, including quality of life assessment and a comprehensive assessment of potential predictive factors for chronic pain prior to surgery. Post-operatively pain symptoms will be monitored using short daily and weekly questionnaires taken by m-health and e-health techniques to study natural course of pain. A comprehensive assessment of pain, quality of life, and medical consumption will be taken at 3,6, and 12 months post-operatively.

In phase two of the study patients who developed chronic pain will be invited for mapping of adhesions using cineMRI. Results of mapping of adhesions using cineMRI in patients with chronic abdominal pain will be compared to mapping of adhesions in 100 patients matched for type of surgery and risk factors who did not develop chronic pain.

Study population: 1,500 patients undergoing elective abdominal surgery from different surgical subspecialties (e.g. colorectal, upper-GI, and gynaecological surgery), aged 18 years or older.

Main study parameters/endpoints: Main study outcome for phase one are risk factors for development of chronic pain at 12 months post-operative. Pivotal secondary outcomes include description of the median duration (days) of moderate to severe abdominal pain following abdominal surgery, and modelling of factors that impact change in abdominal pain after surgery. Other secondary outcomes include health-related quality of life, healthcare utilization, and return to daily activity or work.

Main outcomes for phase two is the percentage of patients with adhesions on cineMRI as compared between patients with and without chronic pain. Secondary outcomes relate to the appearance of adhesions on cineMRI, and included extent and the loss of shear.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: In phase one of this cohort study patients will be asked to fill repeated questionnaires on pain and potential risk factors for chronic pain. The intake questionnaire prior to surgery will take approximately 60 minutes to fill. Post-operatively we will send short questionnaires that take 2-5 minutes to fill. These questionnaires will be send daily during the first 60 days after surgery and weekly afterwards. A more comprehensive questionnaire on abdominal pain and complaints that takes 45 minutes to complete will be send at 3,6, and 12 months post-operative. There are no risks related to participation in this study, nor are there direct benefits.

Patients participating in part two of this cohort will undergo cineMRI to evaluate if pain symptoms might relate to adhesions form previous surgery. The MRI will take approximately 20 minutes to perform. MRI is a non-invasive imaging technique without health risks. However, there is a risk of incidental findings that do not relate to the subject of this study (adhesion formation). Patients who do not want to be informed about incidental findings will be excluded from phase two. In a subset female patients who had pelvic surgery and resection of the uterus an additional transvaginal ultrasound will be made. Like MRI, this is a non-invasive diagnostic test without health risks. There is some additional inconvenience by the use of a transvaginal ultrasound prove. The test will take approximately 15 min.

Eligibility criteria: In order to be eligible to participate in this study, a subject must meet all of the following criteria:

* Adult patients, aged above 18 years
* Planned for elective abdominal surgery, e.g. laparotomy or laparoscopy

For phase two of this study we will recruit patients from the group that participated in phase 1. Additional inclusion criteria for phase two:

* Patients who developed chronic post-operative abdominal pain according to IASP criteria:
* Daily pain in the past three months
* Pain is continues or intermittent
* Pain scores for the worst pain are 4 or higher
* Or patients without chronic pain (n=100) who are propensity matched for type of surgery and risk factors for developing chronic pain.

Exclusion Criteria:

A potential subject who meets any of the following criteria will be excluded from participation in this study:

* Mental incompetence
* Planned for laparoscopic cholecystectomy
* Planned for Caesarean section

Additional exclusion criteria for phase two are:

* Contra-indications for MRI (without contrast) including:
* Severe claustrophobia
* Metal splinters in eyes
* Cerebral vascular clips
* Electronic medical implants
* Patients who do not want to be informed about potential incidental findings of MRI-scan

Primary outcomes:
measure: Risk factors for development of chronic pain
timeFrame: 12 months
measure: Incidence of adhesions on cineMRI in patients with chronic abdominal pain.
timeFrame: 2 months
Secondary outcomes:
measure: incidence of chronic pain
timeFrame: 12 months
measure: Duration of moderate to severe pain
timeFrame: 60 days post surgery
measure: Health-related quality of life
timeFrame: 12 months
measure: Return to daily activity/ work
timeFrame: 12 months
measure: Healthcare utilization
timeFrame: 12 months
measure: characteristics of adhesions on cineMRI
timeFrame: 2 months
Other outcomes:
Locations:
city: Boxmeer
country: Netherlands
facility: Maasziekenhuis Pantein
state: Gelderland
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
state: Gelderland
city: Maastricht
country: Netherlands
facility: Maastricht Universitair Medisch Centrum+
state: Limburg
city: Arnhem
country: Netherlands
facility: Rijnstate Hospital
city: Doetinchem
country: Netherlands
facility: Slingeland Hospital
city: Ede
country: Netherlands
facility: Gelderse Vallei Hospital
city: Nijmegen
country: Netherlands
facility: Canisius Wilhelmina Ziekenhuis
Study officials:
References:
citation: van den Beukel BAW, Stommel MWJ, van Leuven S, Strik C, IJsseldijk MA, Joosten F, van Goor H, Ten Broek RPG. A Shared Decision Approach to Chronic Abdominal Pain Based on Cine-MRI: A Prospective Cohort Study. Am J Gastroenterol. 2018 Aug;113(8):1229-1237. doi: 10.1038/s41395-018-0158-9. Epub 2018 Jun 27.
citation: Strik C, van den Beukel B, van Rijckevorsel D, Stommel MWJ, Ten Broek RPG, van Goor H. Risk of Pain and Gastrointestinal Complaints at 6Months After Elective Abdominal Surgery. J Pain. 2019 Jan;20(1):38-46. doi: 10.1016/j.jpain.2018.07.010. Epub 2018 Aug 11.
citation: Randall D, Joosten F, Ten Broek RP, Gillott R, Bardhan KD, Strik C, Prins W, van Goor H, Fenner JW. A novel diagnostic aid for intra-abdominal adhesion detection in cine-MRI: pilot study and initial diagnostic impressions. Br J Radiol. 2017 Aug;90(1077):20170158. doi: 10.1259/bjr.20170158. Epub 2017 Jul 14.
citation: van den Beukel BA, de Ree R, van Leuven S, Bakkum EA, Strik C, van Goor H, Ten Broek RPG. Surgical treatment of adhesion-related chronic abdominal and pelvic pain after gynaecological and general surgery: a systematic review and meta-analysis. Hum Reprod Update. 2017 May 1;23(3):276-288. doi: 10.1093/humupd/dmx004.