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

February 13, 2024 updated by: Amit Grover, Boston Children's Hospital
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • Morphine, hydromorphone

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
time of enrollment through study completion (approximately 5 days), or transfer to the ICU or initiation of PCA

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
time of enrollment through study completion (approximately 5 days), or transfer to the ICU or initiation of PCA
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.
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 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.
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
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.
duration of trial, approximately 1 year from the start of enrollment
Pain resolution: pain scores
Time Frame: time of enrollment through study completion (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.
time of enrollment through study completion (approximately 5 days), or transfer to the ICU or initiation of PCA

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boston Children's Hospital

Collaborators

The National Pancreas Foundation

Investigators

  • Principal Investigator: Amit Grover, MB BCh BAO, Boston Children's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 15, 2022

Primary Completion (Estimated)

June 30, 2024

Study Completion (Estimated)

June 30, 2024

Study Registration Dates

First Submitted

February 3, 2020

First Submitted That Met QC Criteria

February 28, 2020

First Posted (Actual)

March 2, 2020

Study Record Updates

Last Update Posted (Actual)

February 14, 2024

Last Update Submitted That Met QC Criteria

February 13, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P00034168

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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