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

NCT04291599 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: P00034168
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Pancreatitis

Keywords

Pancreatitis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Safety: 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

• Length of stay

  time of enrollment through study completion (approximately 5 days), or transfer to the ICU or initiation of PCA

• Time to initiation of oral or enteral diet

  time of enrollment through study completion (approximately 5 days), or transfer to the ICU or initiation of PCA

• Predefined Feasibility Outcomes to Assess Trial Success

  duration of trial, approximately 1 year from the start of enrollment

• Pain resolution: pain scores

  time of enrollment through study completion (approximately 5 days), or transfer to the ICU or initiation of PCA

Study Arms (2)

Experimental Arm - Ketorolac (Opioid-Sparing)

EXPERIMENTAL

Patients assigned to this arm of the study will follow the standardized step-up approach to pain management per the hospital Evidenced Based Guideline (EBG). If analgesia is not obtained with first-line medications such as acetaminophen, the patient will be given the NSAID ketorolac intravenously every 6 hours at the standard weight-based dose throughout hospitalization. If the patient experiences continued pain, they (or their guardian/ caregiver) may request a rescue medication in the form of low-dose morphine (or an alternative opioid if allergic to morphine) at 0.025 mg/kg/dose every 4 hours.

Drug: Ketorolac

Control Arm - Conventional Treatment/Standard of Hospital Care

ACTIVE COMPARATOR

Patients assigned to this arm of the study will be treated per institutional policy and procedural care as dictated by established hospital order sets and at the discretion of the provider. This may involve the step-up approach per the hospital EBG utilizing acetaminophen or ibuprofen as first-line agents; however, it remains at the discretion of the treating provider. The current standard of care for children presenting to the ED is based on prescribing order sets within the electronic medical record (EMR). Physicians in the BCH emergency department choose in an intermittently-prescribed manner, standard doses of analgesia including acetaminophen (Tylenol) or ibuprofen per the hospital EBG, as well as opioids (morphine, hydromorphone).

Drug: Opioid

Interventions

Opioid DRUG

Subjects will be randomized to either receive opioid (standard of care) or opioid-sparing analgesia

Also known as: Morphine, hydromorphone

Control Arm - Conventional Treatment/Standard of Hospital Care

Ketorolac DRUG

Subjects will be randomized to either receive opioid (standard of care) or opioid-sparing analgesia.

Also known as: Toradol

Experimental Arm - Ketorolac (Opioid-Sparing)

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)
• Age ≤21 years
• Patient weight ≥8 kg

You may not qualify if:

• Allergy to morphine (and hydromorphone) or aspirin/NSAID
• History of renal or hepatic insufficiency
• History of peptic ulceration
• History of bleeding diathesis
• Pregnant females
• Patients who have a documented history of substance abuse disorder or those who use opioids chronically
• Patients admitted to the Intensive Care Unit (ICU)
• Patients who received intravenous opioid patient-controlled analgesia (PCA) in transit or during their ED admission.

Sponsors & Collaborators

• The National Pancreas Foundation: collaborator
• Boston Children's Hospital: lead

Study Sites (1)

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (17)

• 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.

  PMID: 17032204 BACKGROUND

• 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.

  PMID: 29077648 BACKGROUND

• 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.

  PMID: 23622137 BACKGROUND

• 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.

  PMID: 17484894 BACKGROUND

• 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.

  PMID: 28033313 BACKGROUND

• 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.

  PMID: 11983659 BACKGROUND

• 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.

  PMID: 27580638 BACKGROUND

• 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.

  PMID: 27673455 BACKGROUND

• 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.

  PMID: 21336157 BACKGROUND

• 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.

  PMID: 17489962 BACKGROUND

• 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.

  PMID: 19752770 BACKGROUND

• 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.

  PMID: 24614126 BACKGROUND

• 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.

  PMID: 26504126 BACKGROUND

• 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.

  PMID: 22357117 BACKGROUND

• 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.

  PMID: 18929686 BACKGROUND

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

  PMID: 19565683 BACKGROUND

• 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.

  PMID: 20307699 BACKGROUND

MeSH Terms

Conditions

Pancreatitis

Interventions

Ketorolac; Ketorolac Tromethamine; Analgesics, Opioid; Morphine; Hydromorphone

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Indomethacin; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Central Nervous System Agents; Therapeutic Uses; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Amit Grover, MB BCh BAO

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This will be a phase 2, single-center, unblinded randomized controlled pilot trial of two arms comparing opioid-sparing analgesia to the current BCH 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.

Study Record Dates

• First Submitted: February 3, 2020
• First Posted: March 2, 2020
• Study Start: March 15, 2022
• Primary Completion: July 24, 2025
• Study Completion: July 24, 2025
• Last Updated: January 8, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)