Initial Pain Management in Pediatric Pancreatitis: Opioid vs. Non-Opioid

Acute Pancreatitis Clinical Trial

— PATIENCE  

Official title:

Initial Pain Management in Pediatric Pancreatitis: Opioid vs. Non-Opioid

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04291599
• Other study ID #: P00034168
• Status: Recruiting
• Phase: Phase 2
• Start date: March 15, 2022
• Est. completion date: June 30, 2024

Study information

• Verified date: February 2024
• Source: Boston Children's Hospital
• Contact: Amit Grover, MB BCh BAO
• Phone: 617-355-6058
• Email: Amit.Grover[@]childrens.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This will be a phase 2, single-center, unblinded randomized controlled pilot trial of two arms comparing opioid-sparing analgesia to the current Boston Children's Hospital institutional practice which has been reported to predominantly include administration of opioids as a first-line analgesic to pediatric patients who present to the emergency department with a diagnosis of acute pancreatitis (AP). This is a pilot trial for which many outcomes have not previously been studied in the pediatric AP population. The focus of this investigation will be to investigate the magnitude and variability of effect sizes for designing a future multi-center, double-blinded randomized controlled trial.

Description:

Acute pancreatitis (AP) is the most common pancreatic disease of childhood with an increasing incidence estimated at 13.2 cases in 100,000 children per year. Given the dearth of pediatric literature, most pediatric providers often rely on diagnostic, prognostic and treatment guidelines that have been derived from adults. This is problematic because adult therapeutic guidelines fail to consider the unique age-related responses and requirements of childhood. Pain management is one of the cornerstones in the treatment of pancreatitis, with abdominal pain being the most common presenting symptom of AP. Currently, there are no data on optimal pain management in pediatric AP. Older guidelines suggest that the "use of intravenous patient-controlled analgesia (PCA) is advantageous" as it allows the patient to self-administer opioids and strike a balance between analgesia and side effects. This requires cognitive maturity to understand how to use PCA and poses challenges for younger children, particularly infants and toddlers, as well as pediatric patients with developmental delay. It is particularly concerning that greater than 94% of surveyed pediatric practitioners would use morphine or related opioids as a first-line therapy in children with AP especially when there have been no studies examining the benefits/risks of opioid vs non-opioid analgesics or opioid-sparing therapies in pediatric AP. Furthermore, we recently reported a retrospective analysis demonstrating that opioids are prescribed far more frequently either alone or in combination with non-opioids (70%) than non-opioid alternatives alone (30%). Amongst all types of analgesia prescribed to children who presented to the BCH emergency department (ED) with acute pancreatitis, morphine was the most common. Further research in this area is imperative, particularly given the recent opioid epidemic. From a pediatric perspective, it has been demonstrated that adolescents are amongst those at risk for opioid abuse, thus there is an urgent need to determine whether opioids are necessary for the management of pain in this vulnerable population with AP.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 21 Years

Eligibility

Inclusion Criteria:

1. Patients who present to the ED and are admitted to BCH with a diagnosis of acute pancreatitis or an acute bout of chronic pancreatitis based on INSPPIRE14 Criteria (Appendix 1)

2. Age =21 years

3. Patient weight =8 kg

Exclusion Criteria:

1. Allergy to morphine (and hydromorphone) or aspirin/NSAID

2. History of renal or hepatic insufficiency

3. History of peptic ulceration

4. History of bleeding diathesis

5. Pregnant females

6. Patients who have a documented history of substance abuse disorder or those who use opioids chronically

7. Patients admitted to the Intensive Care Unit (ICU)

8. Patients who received intravenous opioid patient-controlled analgesia (PCA) in transit or during their ED admission.

Related Conditions & MeSH terms

• Acute Pancreatitis
• Pancreatitis

Intervention

Drug:
• Ketorolac
Subjects will be randomized to either receive opioid (standard of care) or opioid-sparing analgesia.
• Opioid
Subjects will be randomized to either receive opioid (standard of care) or opioid-sparing analgesia

Locations

Country	Name	City	State
United States	Boston Children's Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Boston Children's Hospital	The National Pancreas Foundation

Country where clinical trial is conducted

United States, 

References & Publications (17)

Abu-El-Haija M, Lin TK, Palermo J. Update to the management of pediatric acute pancreatitis: highlighting areas in need of research. J Pediatr Gastroenterol Nutr. 2014 Jun;58(6):689-93. doi: 10.1097/MPG.0000000000000360. — View Citation

Bai HX, Lowe ME, Husain SZ. What have we learned about acute pancreatitis in children? J Pediatr Gastroenterol Nutr. 2011 Mar;52(3):262-70. doi: 10.1097/MPG.0b013e3182061d75. — View Citation

Banks PA, Freeman ML; Practice Parameters Committee of the American College of Gastroenterology. Practice guidelines in acute pancreatitis. Am J Gastroenterol. 2006 Oct;101(10):2379-400. doi: 10.1111/j.1572-0241.2006.00856.x. No abstract available. — View Citation

Cohen J. A power primer. Psychol Bull. 1992 Jul;112(1):155-9. doi: 10.1037//0033-2909.112.1.155. — View Citation

Forsmark CE, Baillie J; AGA Institute Clinical Practice and Economics Committee; AGA Institute Governing Board. AGA Institute technical review on acute pancreatitis. Gastroenterology. 2007 May;132(5):2022-44. doi: 10.1053/j.gastro.2007.03.065. No abstract available. — View Citation

Grover AS, Mitchell PD, Manzi SF, Fox VL. Initial Pain Management in Pediatric Acute Pancreatitis: Opioid Versus Non-opioid. J Pediatr Gastroenterol Nutr. 2018 Feb;66(2):295-298. doi: 10.1097/MPG.0000000000001809. — View Citation

Hadland SE, Wood E, Levy S. How the paediatric workforce can address the opioid crisis. Lancet. 2016 Sep 24;388(10051):1260-1. doi: 10.1016/S0140-6736(16)31573-2. No abstract available. — View Citation

Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009 Apr;42(2):377-81. doi: 10.1016/j.jbi.2008.08.010. Epub 2008 Sep 30. — View Citation

Howard ML, Isaacs AN, Nisly SA. Continuous Infusion Nonsteroidal Anti-Inflammatory Drugs for Perioperative Pain Management. J Pharm Pract. 2018 Feb;31(1):66-81. doi: 10.1177/0897190016665539. Epub 2016 Aug 31. — View Citation

Huguet A, Stinson JN, McGrath PJ. Measurement of self-reported pain intensity in children and adolescents. J Psychosom Res. 2010 Apr;68(4):329-36. doi: 10.1016/j.jpsychores.2009.06.003. Epub 2009 Oct 2. — View Citation

Miech R, Johnston L, O'Malley PM, Keyes KM, Heard K. Prescription Opioids in Adolescence and Future Opioid Misuse. Pediatrics. 2015 Nov;136(5):e1169-77. doi: 10.1542/peds.2015-1364. — View Citation

Morinville VD, Barmada MM, Lowe ME. Increasing incidence of acute pancreatitis at an American pediatric tertiary care center: is greater awareness among physicians responsible? Pancreas. 2010 Jan;39(1):5-8. doi: 10.1097/MPA.0b013e3181baac47. — View Citation

Morinville VD, Husain SZ, Bai H, Barth B, Alhosh R, Durie PR, Freedman SD, Himes R, Lowe ME, Pohl J, Werlin S, Wilschanski M, Uc A; INSPPIRE Group. Definitions of pediatric pancreatitis and survey of present clinical practices. J Pediatr Gastroenterol Nutr. 2012 Sep;55(3):261-5. doi: 10.1097/MPG.0b013e31824f1516. Erratum In: J Pediatr Gastroenterol Nutr. 2013 Apr;56(4):459. Abu-Al-Haija, Maisam [corrected to Abu-El-Haija, Maisam]. — View Citation

Munro HM, Walton SR, Malviya S, Merkel S, Voepel-Lewis T, Loder RT, Farley FA. Low-dose ketorolac improves analgesia and reduces morphine requirements following posterior spinal fusion in adolescents. Can J Anaesth. 2002 May;49(5):461-6. doi: 10.1007/BF03017921. — View Citation

Nydegger A, Heine RG, Ranuh R, Gegati-Levy R, Crameri J, Oliver MR. Changing incidence of acute pancreatitis: 10-year experience at the Royal Children's Hospital, Melbourne. J Gastroenterol Hepatol. 2007 Aug;22(8):1313-6. doi: 10.1111/j.1440-1746.2007.04936.x. Epub 2007 Apr 19. — View Citation

Rudd RA, Seth P, David F, Scholl L. Increases in Drug and Opioid-Involved Overdose Deaths - United States, 2010-2015. MMWR Morb Mortal Wkly Rep. 2016 Dec 30;65(50-51):1445-1452. doi: 10.15585/mmwr.mm655051e1. — View Citation

Wu BU, Banks PA. Clinical management of patients with acute pancreatitis. Gastroenterology. 2013 Jun;144(6):1272-81. doi: 10.1053/j.gastro.2013.01.075. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy: amount of opioid analgesia (mg/kg/hr) from the time of enrollment until discharge home, transfer to the ICU, or initiation of PCA	The primary endpoint for efficacy is the amount of opioid analgesia (mg/kg/hr) from the time of enrollment until discharge home, transfer to the ICU, or initiation of PCA.	time of enrollment through study completion (approximately 5 days), or transfer to the ICU or initiation of PCA
Secondary	Safety: number of hours from the time of enrollment until discharge home, transfer to the ICU, or initiation of PCA	The secondary endpoint for safety is defined as the total number of incident adverse events, grade 2 or higher, from the time of enrollment until discharge home, transfer to the ICU, or initiation of PCA.	time of enrollment through study completion (approximately 5 days), or transfer to the ICU or initiation of PCA
Secondary	Length of stay	The secondary endpoint for length of stay is defined as the number of hours from the time of enrollment until discharge home, transfer to the ICU, or initiation of PCA.	time of enrollment through study completion (approximately 5 days), or transfer to the ICU or initiation of PCA
Secondary	Time to initiation of oral or enteral diet	The secondary endpoint for time to initiation of oral or enteral diet is defined as the number of hours from the time of enrollment until first oral or enteral intake. The number of hours will be expressed to two decimal places to account for fractions of an hour.	time of enrollment through study completion (approximately 5 days), or transfer to the ICU or initiation of PCA
Secondary	Predefined Feasibility Outcomes to Assess Trial Success	The secondary endpoint for feasibility is defined as (1) =80% of eligible patients approached for consent during the trial, and (2) =20% of eligible patients randomized into the trial.	duration of trial, approximately 1 year from the start of enrollment
Secondary	Pain resolution: pain scores	To compare pain resolution from time of enrollment throughout hospital stay by comparing pain scores in patients receiving opioid-sparing therapies to those receiving standard of care opioid analgesics.	time of enrollment through study completion (approximately 5 days), or transfer to the ICU or initiation of PCA