## Protocol Section
### Identification Module
**NCT ID:** NCT06417528

**Acronym:** CPoP

**Brief Title:** Chronic Postsurgical Pain: Multivariate Prediction Model

**Official Title:** Chronic Postsurgical Pain: Multivariate Prediction Model

#### Organization Study ID Info
**ID:** CPoP
#### Organization
**Class:** OTHER
**Full Name:** Societa Italiana Anestesia Analgesia Rianimazione e Terapia Intensiva
### Status Module
#### Completion Date
**Date:** 2025-06-14

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-16

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-11

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2024-12-14

**Type:** ESTIMATED

#### Start Date
**Date:** 2022-12-14

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-16
**Type:** ACTUAL
**Study First Submit Date:** 2024-03-19
**Study First Submit QC Date:** 2024-05-11
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Societa Italiana Anestesia Analgesia Rianimazione e Terapia Intensiva

#### Responsible Party

**Investigator Affiliation:** Societa Italiana Anestesia Analgesia Rianimazione e Terapia Intensiva

**Investigator Full Name:** Luigi Cardia

**Investigator Title:** Principal Investigator

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** The goal of this observational study is to identify the risk factors of Chronic Postoperative pain (or Chronic Post Surgery Pain - CPSP) three months after surgery and, subsequently. the development of a risk index to identify high-risk patients considering the multifactorial etiology of CPOP in adult patients undergoing any type of elective surgery.

**Detailed Description:** The study aims to identify the risk factors of CPSP three months after surgery and subsequently develop a risk index to identify high-risk patients considering the multifactorial etiology of CPSP.

A comprehensive entry pool was derived from a systematic literature search. Data collection will record parameters at four different time points: preoperative assessment (60 to 1 day before the scheduled procedure); evaluation of the perioperative period; postoperative period (from the third month after the operation).

The outcome variable is the presence of CPSP assessed 3 months postoperatively and defined as a mean pain intensity of at least 3 on the NRS (one-dimensional pain scale from 0 to 10) over the past three days and pain localized to the field surgical (or to the area of the lesion) projected into the innervation territory of a nerve located in this area, or referred to a dermatome.

Four separate forecasting models will be developed using data derived from surveys carried out at relevant time points for the development of the risk index.

### Conditions Module

**Conditions:**

- Post Surgical Pain

- Post Operative Pain

- Postoperative Pain, Chronic

**Keywords:**

- Pain

- Chronic Pain

- Postoperative Pain

- Post Operative Pain

- Post Surgical Pain

- Multivariate Prediction Model

- Prediction Model

### Design Module

#### Design Info

**Observational Model:** COHORT

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 1500

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Data collection will record parameters of patients undergoing surgery at four different times: preoperative assessment (60 to 1 day before the scheduled procedure); evaluation of the perioperative period; and postoperative period (from the third month following surgery).

**Intervention Names:**

- Procedure: Chronic Post Surgery Pain (CPSP)

**Label:** Surgery Patients

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Surgery Patients

**Description:** The outcome variable is the presence of CPSP assessed 3 months after surgery and defined as an average pain intensity of at least 3 on the NRS scale (11-point one-dimensional pain scale) in the last three days, and pain localized to the surgical field (or in the lesion area) projected into the innervation territory of a nerve located in this area or referred to a dermatome.

Separate prediction models will be developed using data derived from surveys conducted at the relevant time points for the development of the risk index.

**Name:** Chronic Post Surgery Pain (CPSP)

**Type:** PROCEDURE

### Outcomes Module

#### Other Outcomes

**Description:** * Primary version of the risk index, made up of items derived from a systematic bibliographic search (compilation of the item pool).
* Authors will analyze the associations between each of these indices and the probability of CPSP 3 months after surgery (dichotomous variable), evaluated using logistic regression models.
* Items that were found to be significant in the bivariate analyses will then be analyzed multivariately (logistic regression models).
* Authors will safeguard the results of the multivariate analyses by calculating the area under the ROC curve of the model, and then, the cut-off score for a high risk of developing CPSP will be identified with an optimal compromise between sensitivity and specificity.
* The items that will generate significant predictive factors in the logistic regression analyses will be collected into an index. For each value of this index, the Authors will calculate the proportion of patients who reported CPSP at 3 months after surgery.

**Measure:** Development of the risk index

**Time Frame:** 6 months after the primary completion of the study

#### Primary Outcomes

**Description:** Presence of CPSP assessed 3 months after surgery and defined as an average pain intensity of at least 3 points on the NRS scale (one-dimensional pain scale - from 0 to 10 points) in the last three days and pain localized to the surgical field (or in the lesion area) projected into the innervation territory of a nerve located in this area, or referred to a dermatome.

**Measure:** Chronic Post Surgery Pain (CPSP)

**Time Frame:** 3 months

#### Secondary Outcomes

**Description:** * Age

  * 18-35
  * 36-55
  * ≥55
* Sex

  * Female
  * Male
* BMI

  * ≤18.5 - 24.9
  * 25 - 29.9
  * ≥30
* Alcohol or substances of abuse (Y/N) (specify the substance)
* Previous experience of pain NRS ≥5 for 7 days (Y/N)
* Presence of chronic pathologies (Y/N) (if yes, provide the list of medications)
* Pharmacological treatments including supplements or nutraceuticals (continuous in the last 3 months) (Y/N) (if yes, provide the list of drugs)
* Chronic pain (NRS ≥3 for ≥3 months) (Y/N)
* Neuropathic pain (Y/N) (assessment using Douleur Neuropathique en 4 questions DN-4 questionnaire)
* Pain catastrophizing (Y/N) (assessment via Pain Catastrophizing Scale PCS questionnaire)
* Anxiety (Y/N) (assessment using General Anxiety Disorder-7 GAD-7 questionnaire)
* Depression (Y/N) (assessment using Beck Depression Inventory BDI-II questionnaire)
* Presence of pain in the last three days (NRS ≥3 mean pain intensity in the 24 hours) (Y/N)

**Measure:** Pre operative factors

**Time Frame:** 60 to 1 day before the scheduled procedure

**Description:** * Site of surgery

  * Head
  * Vertebral column
  * Arms/legs
  * Chest
  * Abdomen
  * Genitourinary system
* Surgical technique

  * Open surgery
  * Minimally invasive surgery
  * Robotic surgery
* ERAS (enhanced recovery after surgery) protocol (Y/N)
* Anesthesiologic technique

  * General Anesthesia
  * Spinal Anesthesia
  * Epidural Anesthesia
  * Peripheral nerve block
* Preventive/protective analgesia (Y/N)
* Premedication (Y/N)
* OFA opioid-free anesthesia protocol (Y/N)
* Postoperative analgesic prescription (Y/N)

**Measure:** Perioperative factors - before surgery

**Time Frame:** The day of the scheduled surgery - before the surgery

**Description:** * Pain NRS score ≥3 at the end of the surgery (Y/N)
* Presence of pain (NRS ≥5 - average value in the 24 hours) in the region of the operation at rest or during movement after surgery (Y/N)
* Analgesic prescription after surgery

  * ≤12 hours of coverage
  * 13-24 hours of coverage
  * ≥ 24 hours of coverage
* Postoperative surgical complications (Y/N)
* Postoperative infectious complications (Y/N)
* Mobilization after surgery ≤6 hours? (Y/N)

**Measure:** Perioperative factors - after surgery

**Time Frame:** Immediately after the surgery to 48 hours after the surgery

**Description:** * Pain assessment: average pain intensity assessed using a standard NRS scale (the cutoff score will be set at ≥3 mean pain intensity over the last three days ) (Y/N).
* Diagnosis of CPSP (the pain is localized in the surgical field or in the area of the lesion, projected into the innervation territory of a nerve located in this area, or referred to a dermatome) (Y/N)
* Surgical complications (Y/N)
* Infectious complications related to surgery (Y/N)
* Malignancy (Y/N)
* Neuropathic pain (Y/N) (assessed using Douleur Neuropathique in 4 questions DN-4 questionnaire)

**Measure:** Post operative factors

**Time Frame:** 3 months after surgery

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Adult Patients
* Patients undergoing any type of elective surgery

Exclusion Criteria:

* Patients with sensory impairments
* Patients unable to communicate
* Patients with cognitive impairments
* Patients with insufficent knowledge of the language

**Healthy Volunteers:** True

**Minimum Age:** 18 Years

**Sampling Method:** PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

**Study Population:** Adult patients undergoing any type of elective surgery

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** lcardia@unime.it

**Name:** Luigi Cardia, MD; PhD

**Phone:** +39 340 6946866

**Role:** CONTACT

**Contact 2:**

**Email:** alberto.noto@unime.it

**Name:** Alberto Noto, MD; PhD

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Messina

**Contacts:**

***Contact 1:***

- **Name:** Luigi Cardia, MD: PhD

- **Role:** CONTACT

**Country:** Italy

**Facility:** AOU G. Martino

**Status:** RECRUITING

### References Module

#### References

**Citation:** Treede RD, Rief W, Barke A, Aziz Q, Bennett MI, Benoliel R, Cohen M, Evers S, Finnerup NB, First MB, Giamberardino MA, Kaasa S, Kosek E, Lavand'homme P, Nicholas M, Perrot S, Scholz J, Schug S, Smith BH, Svensson P, Vlaeyen JWS, Wang SJ. A classification of chronic pain for ICD-11. Pain. 2015 Jun;156(6):1003-1007. doi: 10.1097/j.pain.0000000000000160. No abstract available.

**PMID:** 25844555

**Citation:** Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet. 2006 May 13;367(9522):1618-25. doi: 10.1016/S0140-6736(06)68700-X.

**PMID:** 16698416

**Citation:** Macrae WA. Chronic post-surgical pain: 10 years on. Br J Anaesth. 2008 Jul;101(1):77-86. doi: 10.1093/bja/aen099. Epub 2008 Apr 22.

**PMID:** 18434337

**Citation:** Breivik H, Collett B, Ventafridda V, Cohen R, Gallacher D. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain. 2006 May;10(4):287-333. doi: 10.1016/j.ejpain.2005.06.009. Epub 2005 Aug 10.

**PMID:** 16095934

**Citation:** Goldberg DS, McGee SJ. Pain as a global public health priority. BMC Public Health. 2011 Oct 6;11:770. doi: 10.1186/1471-2458-11-770.

**PMID:** 21978149

**Citation:** Phillips CJ. Economic burden of chronic pain. Expert Rev Pharmacoecon Outcomes Res. 2006 Oct;6(5):591-601. doi: 10.1586/14737167.6.5.591.

**PMID:** 20528505

**Citation:** Fletcher D, Stamer UM, Pogatzki-Zahn E, Zaslansky R, Tanase NV, Perruchoud C, Kranke P, Komann M, Lehman T, Meissner W; euCPSP group for the Clinical Trial Network group of the European Society of Anaesthesiology. Chronic postsurgical pain in Europe: An observational study. Eur J Anaesthesiol. 2015 Oct;32(10):725-34. doi: 10.1097/EJA.0000000000000319.

**PMID:** 26241763

**Citation:** Turk DC, Fillingim RB, Ohrbach R, Patel KV. Assessment of Psychosocial and Functional Impact of Chronic Pain. J Pain. 2016 Sep;17(9 Suppl):T21-49. doi: 10.1016/j.jpain.2016.02.006.

**PMID:** 27586830

**Citation:** Gerbershagen HJ, Dagtekin O, Rothe T, Heidenreich A, Gerbershagen K, Sabatowski R, Petzke F, Ozgur E. Risk factors for acute and chronic postoperative pain in patients with benign and malignant renal disease after nephrectomy. Eur J Pain. 2009 Sep;13(8):853-60. doi: 10.1016/j.ejpain.2008.10.001. Epub 2008 Nov 14.

**PMID:** 19010073

**Citation:** Mathes T, Pape-Kohler C, Moerders L, Lux E, Neugebauer EAM. External Validation and Update of the RICP-A Multivariate Model to Predict Chronic Postoperative Pain. Pain Med. 2018 Aug 1;19(8):1674-1682. doi: 10.1093/pm/pnx242.

**PMID:** 29121211

**Citation:** Althaus A, Hinrichs-Rocker A, Chapman R, Arranz Becker O, Lefering R, Simanski C, Weber F, Moser KH, Joppich R, Trojan S, Gutzeit N, Neugebauer E. Development of a risk index for the prediction of chronic post-surgical pain. Eur J Pain. 2012 Jul;16(6):901-10. doi: 10.1002/j.1532-2149.2011.00090.x. Epub 2011 Dec 23.

**PMID:** 22337572

**Citation:** Sangesland A, Storen C, Vaegter HB. Are preoperative experimental pain assessments correlated with clinical pain outcomes after surgery? A systematic review. Scand J Pain. 2017 Apr;15:44-52. doi: 10.1016/j.sjpain.2016.12.002. Epub 2016 Dec 19.

**PMID:** 28850344

**Citation:** Siao P, Cros DP. Quantitative sensory testing. Phys Med Rehabil Clin N Am. 2003 May;14(2):261-86. doi: 10.1016/s1047-9651(02)00122-5.

**PMID:** 12795516

**Citation:** Ip HY, Abrishami A, Peng PW, Wong J, Chung F. Predictors of postoperative pain and analgesic consumption: a qualitative systematic review. Anesthesiology. 2009 Sep;111(3):657-77. doi: 10.1097/ALN.0b013e3181aae87a.

**PMID:** 19672167

**Citation:** Werner MU, Mjobo HN, Nielsen PR, Rudin A. Prediction of postoperative pain: a systematic review of predictive experimental pain studies. Anesthesiology. 2010 Jun;112(6):1494-502. doi: 10.1097/ALN.0b013e3181dcd5a0.

**PMID:** 20460988

**Citation:** Abrishami A, Chan J, Chung F, Wong J. Preoperative pain sensitivity and its correlation with postoperative pain and analgesic consumption: a qualitative systematic review. Anesthesiology. 2011 Feb;114(2):445-57. doi: 10.1097/ALN.0b013e3181f85ed2.

**PMID:** 21245740

**Citation:** Kuner R, Flor H. Structural plasticity and reorganisation in chronic pain. Nat Rev Neurosci. 2016 Dec 15;18(1):20-30. doi: 10.1038/nrn.2016.162. Erratum In: Nat Rev Neurosci. 2017 Feb;18(2):158. Nat Rev Neurosci. 2017 Jan 20;18(2):113.

**PMID:** 27974843

**Citation:** Glare P, Aubrey KR, Myles PS. Transition from acute to chronic pain after surgery. Lancet. 2019 Apr 13;393(10180):1537-1546. doi: 10.1016/S0140-6736(19)30352-6.

**PMID:** 30983589

**Citation:** Campos ACP, Antunes GF, Matsumoto M, Pagano RL, Martinez RCR. Neuroinflammation, Pain and Depression: An Overview of the Main Findings. Front Psychol. 2020 Jul 31;11:1825. doi: 10.3389/fpsyg.2020.01825. eCollection 2020.

**PMID:** 32849076

**Citation:** Tsepilov YA, Freidin MB, Shadrina AS, Sharapov SZ, Elgaeva EE, Zundert JV, Karssen Lcapital ES, Cyrillic, Suri P, Williams FMK, Aulchenko YS. Analysis of genetically independent phenotypes identifies shared genetic factors associated with chronic musculoskeletal pain conditions. Commun Biol. 2020 Jun 25;3(1):329. doi: 10.1038/s42003-020-1051-9.

**PMID:** 32587327

**Citation:** Crofford LJ. Chronic Pain: Where the Body Meets the Brain. Trans Am Clin Climatol Assoc. 2015;126:167-83.

**PMID:** 26330672

**Citation:** Diatchenko L, Fillingim RB, Smith SB, Maixner W. The phenotypic and genetic signatures of common musculoskeletal pain conditions. Nat Rev Rheumatol. 2013 Jun;9(6):340-50. doi: 10.1038/nrrheum.2013.43. Epub 2013 Apr 2.

**PMID:** 23545734

**Citation:** Kalkman JC, Visser K, Moen J, Bonsel JG, Grobbee ED, Moons MKG. Preoperative prediction of severe postoperative pain. Pain. 2003 Oct;105(3):415-423. doi: 10.1016/S0304-3959(03)00252-5.

**PMID:** 14527702

**Citation:** Fillingim RB, King CD, Ribeiro-Dasilva MC, Rahim-Williams B, Riley JL 3rd. Sex, gender, and pain: a review of recent clinical and experimental findings. J Pain. 2009 May;10(5):447-85. doi: 10.1016/j.jpain.2008.12.001.

**PMID:** 19411059

**Citation:** Wang L, Guyatt GH, Kennedy SA, Romerosa B, Kwon HY, Kaushal A, Chang Y, Craigie S, de Almeida CPB, Couban RJ, Parascandalo SR, Izhar Z, Reid S, Khan JS, McGillion M, Busse JW. Predictors of persistent pain after breast cancer surgery: a systematic review and meta-analysis of observational studies. CMAJ. 2016 Oct 4;188(14):E352-E361. doi: 10.1503/cmaj.151276. Epub 2016 Jul 11.

**PMID:** 27402075

**Citation:** Theunissen M, Peters ML, Bruce J, Gramke HF, Marcus MA. Preoperative anxiety and catastrophizing: a systematic review and meta-analysis of the association with chronic postsurgical pain. Clin J Pain. 2012 Nov-Dec;28(9):819-41. doi: 10.1097/AJP.0b013e31824549d6.

**PMID:** 22760489

**Citation:** Hinrichs-Rocker A, Schulz K, Jarvinen I, Lefering R, Simanski C, Neugebauer EA. Psychosocial predictors and correlates for chronic post-surgical pain (CPSP) - a systematic review. Eur J Pain. 2009 Aug;13(7):719-30. doi: 10.1016/j.ejpain.2008.07.015. Epub 2008 Oct 25.

**PMID:** 18952472

**Citation:** Meretoja TJ, Andersen KG, Bruce J, Haasio L, Sipila R, Scott NW, Ripatti S, Kehlet H, Kalso E. Clinical Prediction Model and Tool for Assessing Risk of Persistent Pain After Breast Cancer Surgery. J Clin Oncol. 2017 May 20;35(15):1660-1667. doi: 10.1200/JCO.2016.70.3413. Epub 2017 Mar 13.

**PMID:** 28524782

**Citation:** Fink R. Pain assessment: the cornerstone to optimal pain management. Proc (Bayl Univ Med Cent). 2000 Jul;13(3):236-9. doi: 10.1080/08998280.2000.11927681.

**PMID:** 16389388

**Citation:** Caraceni A, Mendoza TR, Mencaglia E, Baratella C, Edwards K, Forjaz MJ, Martini C, Serlin RC, de Conno F, Cleeland CS. A validation study of an Italian version of the Brief Pain Inventory (Breve Questionario per la Valutazione del Dolore). Pain. 1996 Apr;65(1):87-92. doi: 10.1016/0304-3959(95)00156-5.

**PMID:** 8826494

**Citation:** Lempa M, Koch G, Neugebauer E, Kohler L, Troidl H. [How much pain is tolerable? Target expectations of surgical patients for pain therapy]. Chirurg. 2000 Oct;71(10):1263-9. doi: 10.1007/s001040051213. German.

**PMID:** 11077589

**Citation:** Vittinghoff E, McCulloch CE. Relaxing the rule of ten events per variable in logistic and Cox regression. Am J Epidemiol. 2007 Mar 15;165(6):710-8. doi: 10.1093/aje/kwk052. Epub 2006 Dec 20.

**PMID:** 17182981

**Citation:** Riley RD, Ensor J, Snell KIE, Harrell FE Jr, Martin GP, Reitsma JB, Moons KGM, Collins G, van Smeden M. Calculating the sample size required for developing a clinical prediction model. BMJ. 2020 Mar 18;368:m441. doi: 10.1136/bmj.m441. No abstract available.

**PMID:** 32188600

## Document Section

### Large Document Module

#### Large Docs

- Date: 2023-11-02

- Filename: Prot_SAP_000.pdf

- Has ICF: False

- Has Protocol: True

- Has SAP: True

- Label: Study Protocol and Statistical Analysis Plan

- Size: 334277

- Type Abbrev: Prot_SAP

- Upload Date: 2024-03-08T05:38

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000011183

- Term: Postoperative Complications

- ID: D000010335

- Term: Pathologic Processes

- ID: D000010146

- Term: Pain

- ID: D000009461

- Term: Neurologic Manifestations

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M13069

- Name: Pain, Postoperative

- Relevance: HIGH

- As Found: Postoperative Pain, Chronic

- ID: M29442

- Name: Chronic Pain

- Relevance: HIGH

- As Found: Pain, Chronic

- ID: M13066

- Name: Pain

- Relevance: LOW

- As Found: Unknown

- ID: M14065

- Name: Postoperative Complications

- Relevance: LOW

- As Found: Unknown

- ID: M12404

- Name: Neurologic Manifestations

- Relevance: LOW

- As Found: Unknown

- ID: T1303

- Name: Chronic Graft Versus Host Disease

- Relevance: HIGH

- As Found: Chronic

### Condition Browse Module - Meshes

- ID: D000010149

- Term: Pain, Postoperative

- ID: D000059350

- Term: Chronic Pain

### Misc Info Module

- Version Holder: 2024-05-31
