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

• ClinicalTrials.gov Identifier: NCT01380197
• Recruitment Status: Completed
• First Posted: June 27, 2011
• Results First Posted: February 16, 2015
• Last Update Posted: February 20, 2018
• Sponsor: Children's Healthcare of Atlanta
• Collaborator: Atlanta Clinical and Translational Science Institute
• Information provided by (Responsible Party): Saadia Khizer, Children's Healthcare of Atlanta

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Pain; Sickle Cell Disease	Drug: Morphine; Drug: Nubain	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Choosing Opioid Management for Pain and Analyzing ACS Rates Equally
• Actual Study Start Date: May 26, 2010
• Actual Primary Completion Date: January 14, 2014
• Actual Study Completion Date: October 18, 2016

Arms and Interventions

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).

Outcome Measures

Primary Outcome Measures :

1. Acute Chest Syndrome [ Time Frame: 3 days ]
   Number of Participants with Acute Chest Syndrome or A new pulmonry infiltrate on Chest X-ray

Secondary Outcome Measures :

1. Number of Participants Who Experienced Pain Relief [ Time Frame: 2 days ]

Eligibility Criteria

• Ages Eligible for Study: 6 Years to 19 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Georgia

Children's Healthcare of Atlanta

Atlanta, Georgia, United States, 30303

Sponsors and Collaborators

Children's Healthcare of Atlanta

Atlanta Clinical and Translational Science Institute

More Information

• Responsible Party: Saadia Khizer, Iris Buchanan MD, Children's Healthcare of Atlanta
• ClinicalTrials.gov Identifier: NCT01380197
• Other Study ID Numbers: 09-076
• First Posted: June 27, 2011
• Results First Posted: February 16, 2015
• Last Update Posted: February 20, 2018
• Last Verified: January 2018

Keywords provided by Saadia Khizer, Children's Healthcare of Atlanta:

pain; sickle cell; nubain; morphine; acute chest; side effects

Additional relevant MeSH terms:

Anemia, Sickle Cell; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Morphine; Analgesics, Opioid; Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents