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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04291599
Recruitment Status : Not yet recruiting
First Posted : March 2, 2020
Last Update Posted : December 10, 2020
Sponsor:
Collaborator:
The National Pancreas Foundation
Information provided by (Responsible Party):
Amit Grover, Boston Children's Hospital

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.

Condition or disease Intervention/treatment Phase
Acute Pancreatitis Drug: Ketorolac Drug: Opioid Phase 2

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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.
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Initial Pain Management in Pediatric Pancreatitis: Opioid vs. Non-Opioid
Estimated Study Start Date : January 1, 2021
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : February 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Ketorolac

Arm Intervention/treatment
Experimental: Experimental Arm - Ketorolac (Opioid-Sparing)
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
Subjects will be randomized to either receive opioid (standard of care) or opioid-sparing analgesia.
Other Name: Toradol

Active Comparator: Control Arm - Conventional Treatment/Standard of Hospital Care
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
Subjects will be randomized to either receive opioid (standard of care) or opioid-sparing analgesia
Other Name: Morphine, hydromorphone




Primary Outcome Measures :
  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 [ Time Frame: time of enrollment through study completion (approximately 5 days), or 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.


Secondary Outcome Measures :
  1. Safety: number of hours from the time of enrollment until discharge home, transfer to the ICU, or initiation of PCA [ Time Frame: time of enrollment through study completion (approximately 5 days), or 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.

  2. Length of stay [ Time Frame: time of enrollment through study completion (approximately 5 days), or transfer to the ICU or initiation of PCA ]
    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.

  3. Time to initiation of oral or enteral diet [ Time Frame: time of enrollment through study completion (approximately 5 days), or transfer to the ICU or initiation of PCA ]
    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.

  4. Predefined Feasibility Outcomes to Assess Trial Success [ Time Frame: duration of trial, approximately 1 year from the start of enrollment ]
    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.

  5. Pain resolution: pain scores [ Time Frame: time of enrollment through study completetion (approximately 5 days), or transfer to the ICU or initiation of PCA ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 admitted via transfer to BCH from another hospital (ED or inpatient)
  9. Patients who received intravenous opioid patient-controlled analgesia (PCA) in transit or during their ED admission.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04291599


Contacts
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Contact: Amit Grover, MB BCh BAO 617-355-6058 Amit.Grover@childrens.harvard.edu
Contact: Shannon Manzi, PharmD 617-355-2837 Shannon.Manzi@childrens.harvard.edu

Sponsors and Collaborators
Boston Children's Hospital
The National Pancreas Foundation
Investigators
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Principal Investigator: Amit Grover, MB BCh BAO Boston Children's Hospital
Publications:

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Responsible Party: Amit Grover, Principal Investigator, Boston Children's Hospital
ClinicalTrials.gov Identifier: NCT04291599    
Other Study ID Numbers: P00034168
First Posted: March 2, 2020    Key Record Dates
Last Update Posted: December 10, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Amit Grover, Boston Children's Hospital:
Pancreatitis
Additional relevant MeSH terms:
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Pancreatitis
Pancreatic Diseases
Digestive System Diseases
Ketorolac
Morphine
Hydromorphone
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action