Choosing Opioid Management for Pain and Analyzing Acute Chest Syndrome (ACS) Rates Equally (COMPARE)

Choosing Opioid Management for Pain and Analyzing ACS Rates Equally

The pathophysiology of sickle cell disease (SCD) manifestations, are complex with interactions of intracellular hemoglobin, membrane and endothelial activation but the hallmark remains recurrent and painful vaso-occlusive episodes (VOC). These painful episodes are thought to result from ischemia caused when small blood vessels are occluded by misshapen, inflexible erythrocytes. Painful episodes are the most common cause of hospitalization, morbidity, and impairment for SCD patients. There is no therapy that completely prevents or directly aborts painful events for all patients. Consequently, treatment for acute VOC is primarily supportive using hydration and medicinal pain control. Every pain medication has the potential to relieve pain but is associated with significant limitations and side effects.

The primary hypothesis to be tested in this double blind, randomized controlled trial is that Nalbuphine is equivalent to morphine for pain control and patients will suffer fewer episodes of acute chest syndrome. The investigators also expect subjects will report fewer side effects from respiratory depression, abdominal distention from reduced peristalsis, reduced histamine release causing pruritis and still be provided adequate pain control. Further hypotheses to be tested is ability to recruit patient participants while being treated in the Emergency Department and that continuous infusion of Nalbuphine with accompanying patient controlled analgesia (PCA) is safe and effective in controlling pain, requiring less total opiates consumption, while decreasing length of hospitalization.

Study Overview

• Status: Completed
• Conditions: Pain; Sickle Cell Disease
• Intervention / Treatment: Drug: Morphine; Drug: Nubain

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Children's Healthcare of Atlanta

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 17 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with sickle cell disease (SS, SC, SβThal) who are hospitalized for acute painful episodes
• 6 years old and < 19 years old
• Normal baseline chest radiograph
• Normal renal and hepatic function within the previous 12 months

Exclusion Criteria:

• Previous patient participation in this clinical trial
• Any patient on chronic transfusion Any patient with pulmonary infiltrate on chest radiograph on admission
• Any patient with DSM diagnosis, excluding those with Attention Deficit Disorder, on or off treatment
• Any patient with documented allergy to either study drug

• Any patient with known evidence of an underlying disease that would interfere with evaluation of a therapeutic response such as:

  • Hepatic dysfunction (3x ALT),
  • Renal dysfunction (Cr > 1 children/adolescents, Cr >2 adults),
  • Pulmonary Hypertension (TRJ >3.0),
  • Cardiac dysfunction.
  • Any patient with symptoms of an acute stroke.
  • Any patient known or suspected to be pregnant.
  • Any patient with priapism
  • The patient or guardian who will not give consent or assent to be randomized.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Randomizing particiipants to Morphine; Randomizing participants to Morphine or Nubain for treatment of Sickle Cell Pain Crisis	Drug: Morphine; Loading Dose: 0.1mg/kg. May repeat every 15 min up to a maximum of 3 total doses until pain controlled. Continuous rate: 0.01-0.04mg/kg/hr (titrated to comfort level) PCA dose 0.01-0.03 mg/kg maximum 1.6 mg/dose 4 hour dose limit 0.24-0.3 mg/kg (Maximum dosing will not exceed 25 mg/4 hrs).
Active Comparator: Randomization to Nubain; Randomization toNubain or Morphine for the management of Pain Crisis in Sickle Cell patients	Drug: Nubain; Loading Dose: 0.1mg/kg. May repeat every 15 min up to a maximum of 3 total doses until pain controlled. Continuous rate: 0.01-0.04mg/kg/hr (titrated to comfort level) PCA dose 0.01-0.03 mg/kg maximum 1.6 mg/dose 4 hour dose limit 0.24-0.3 mg/kg (Maximum dosing will not exceed 25 mg/4 hrs).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Chest Syndrome	Number of Participants with Acute Chest Syndrome or A new pulmonry infiltrate on Chest X-ray	3 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants Who Experienced Pain Relief	2 days

Collaborators and Investigators

• Sponsor: Children's Healthcare of Atlanta
• Collaborators: Atlanta Clinical and Translational Science Institute

Study record dates

Study Major Dates

• Study Start (Actual): May 26, 2010
• Primary Completion (Actual): January 14, 2014
• Study Completion (Actual): October 18, 2016

Study Registration Dates

• First Submitted: June 22, 2011
• First Submitted That Met QC Criteria: June 23, 2011
• First Posted (Estimate): June 27, 2011

Study Record Updates

• Last Update Posted (Actual): February 20, 2018
• Last Update Submitted That Met QC Criteria: January 23, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: pain; morphine; side effects; sickle cell; nubain; acute chest
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Morphine
• Other Study ID Numbers: 09-076