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

• Sponsor: Children's Healthcare of Atlanta (Other)
• Overall Status: Completed
• CT.gov ID: NCT01380197
• Collaborator: Atlanta Clinical and Translational Science Institute (Other)
• Enrollment: 40
• Location: 1
• Arms: 2
• Actual Duration (Months): 76.8
• Patients Per Site Per Month: 0.5

Study Details

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
• 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: Jan 14, 2014
• Actual Study Completion Date: Oct 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 [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 [2 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 19 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	Children's Healthcare of Atlanta	Atlanta	Georgia	United States	30303

Sponsors and Collaborators

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

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Saadia Khizer, Iris Buchanan MD, Children's Healthcare of Atlanta
• ClinicalTrials.gov Identifier: NCT01380197
• Other Study ID Numbers: 09-076
• First Posted: Jun 27, 2011
• Last Update Posted: Feb 20, 2018
• Last Verified: Jan 1, 2018

• Keywords provided by Saadia Khizer, Iris Buchanan MD, Children's Healthcare of Atlanta: pain; sickle cell; nubain; morphine; acute chest; side effects
• Additional relevant MeSH terms: Anemia, Sickle Cell; Morphine

Study Results

Participant Flow

Arm/Group Title	Randomizing Particiipants to Morphine	Randomization to Nubain
Arm/Group Description	Randomizing participants to Morphine or Nubain for treatment of Sickle Cell Pain Crisis 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).	Randomization toNubain or Morphine for the management of Pain Crisis in Sickle Cell patients 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).
Period Title: Overall Study
STARTED	20	20
COMPLETED	20	20
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Randomizing Particiipants to Morphine	Randomization to Nubain	Total
Arm/Group Description	Randomizing participants to Morphine or Nubain for treatment of Sickle Cell Pain Crisis 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).	Randomization toNubain or Morphine for the management of Pain Crisis in Sickle Cell patients 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).	Total of all reporting groups
Overall Participants	20	20	40
Age (Count of Participants)
<=18 years	20 100%	20 100%	40 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	12 60%	7 35%	19 47.5%
Male	8 40%	13 65%	21 52.5%
Region of Enrollment (participants) [Number]
United States	20 100%	20 100%	40 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Randomizing Particiipants to Morphine	Randomization to Nubain
Arm/Group Description	Randomizing participants to Morphine or Nubain for treatment of Sickle Cell Pain Crisis 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).	Randomization toNubain or Morphine for the management of Pain Crisis in Sickle Cell patients 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).
Measure Participants	20	20
Number [participants]	2 10%	1 5%

2. Secondary Outcome

Title	Number of Participants Who Experienced Pain Relief
Time Frame	2 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Randomizing Particiipants to Morphine	Randomization to Nubain
Arm/Group Description	Randomizing participants to Morphine or Nubain for treatment of Sickle Cell Pain Crisis 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).	Randomization toNubain or Morphine for the management of Pain Crisis in Sickle Cell patients 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).
Measure Participants	20	20
Number [participants]	2 10%	2 10%

Adverse Events

Arm/Group Title	Randomizing Particiipants to Morphine		Randomization to Nubain
Arm/Group Description	Randomizing participants to Morphine or Nubain for treatment of Sickle Cell Pain Crisis 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).		Randomization toNubain or Morphine for the management of Pain Crisis in Sickle Cell patients 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).
All Cause Mortality
	Randomizing Particiipants to Morphine		Randomization to Nubain
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Randomizing Particiipants to Morphine		Randomization to Nubain
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Randomizing Particiipants to Morphine		Randomization to Nubain
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.