Feasibility Study of Unfractionated Heparin in Acute Chest Syndrome

• ClinicalTrials.gov Identifier: NCT02098993
• Recruitment Status: Terminated
• First Posted: March 28, 2014
• Results First Posted: July 16, 2019
• Last Update Posted: July 16, 2019
• Sponsor: Craig Seaman
• Collaborator: Vascular Medicine Institute
• Information provided by (Responsible Party): Craig Seaman, University of Pittsburgh

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Acute Chest Syndrome; Sickle Cell Disease
• Intervention: Drug: Unfractionated heparin
• Enrollment: 7

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Unfractionated Heparin	Standard of Care
Arm/Group Description	Subjects will be randomized within 24 hours of diagnosis to one of two treatment arms, Arm A, anticoagulation and standard of care, or Arm B, no anticoagulation and standard of care. Weight-adjusted UFH will be given at doses of 80 units per kilogram followed by 18 units per kilogram per hour intravenously for 7 days, or until discharge, if discharge is shorter than 7 days. UFH will be monitored by standard protocol to maintain the activated partial thromboplastin time in the therapeutic range per institutional guidelines. The experimental arm will receive standard of care, too, which will include the following: intravenous fluids, antibiotics, supplemental oxygen, incentive spirometry, pain management, red blood cell transfusions, and exchange transfusions. Unfractionated heparin	Standard care will include the following: intravenous fluids, antibiotics, supplemental oxygen, incentive spirometry, pain management, red blood cell transfusions, and exchange transfusions.
Period Title: Overall Study
Started	4	3
Completed	4	3
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		Unfractionated Heparin	Standard of Care	Total
Arm/Group Description		Subjects will be randomized within 24 hours of diagnosis to one of two treatment arms, Arm A, anticoagulation and standard of care, or Arm B, no anticoagulation and standard of care. Weight-adjusted UFH will be given at doses of 80 units per kilogram followed by 18 units per kilogram per hour intravenously for 7 days, or until discharge, if discharge is shorter than 7 days. UFH will be monitored by standard protocol to maintain the activated partial thromboplastin time in the therapeutic range per institutional guidelines. The experimental arm will receive standard of care, too, which will include the following: intravenous fluids, antibiotics, supplemental oxygen, incentive spirometry, pain management, red blood cell transfusions, and exchange transfusions. Unfractionated heparin	Standard care will include the following: intravenous fluids, antibiotics, supplemental oxygen, incentive spirometry, pain management, red blood cell transfusions, and exchange transfusions.	Total of all reporting groups
Overall Number of Baseline Participants		4	3	7
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	4 participants	3 participants	7 participants
		29.25 (3.77)	32 (18.52)	30.43 (11.12)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	4 participants	3 participants	7 participants
	Female	2 50.0%	2 66.7%	4 57.1%
	Male	2 50.0%	1 33.3%	3 42.9%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	4 participants	3 participants	7 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	4 100.0%	3 100.0%	7 100.0%
	White	0 0.0%	0 0.0%	0 0.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%

Outcome Measures

1. Primary Outcome

Title	Time to Hospital Discharge
Description	Duration of hospitalization
Time Frame	Until hospital discharge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Unfractionated Heparin	Standard of Care
Arm/Group Description:	Subjects will be randomized within 24 hours of diagnosis to one of two treatment arms, Arm A, anticoagulation and standard of care, or Arm B, no anticoagulation and standard of care. Weight-adjusted UFH will be given at doses of 80 units per kilogram followed by 18 units per kilogram per hour intravenously for 7 days, or until discharge, if discharge is shorter than 7 days. UFH will be monitored by standard protocol to maintain the activated partial thromboplastin time in the therapeutic range per institutional guidelines. The experimental arm will receive standard of care, too, which will include the following: intravenous fluids, antibiotics, supplemental oxygen, incentive spirometry, pain management, red blood cell transfusions, and exchange transfusions. Unfractionated heparin	Standard care will include the following: intravenous fluids, antibiotics, supplemental oxygen, incentive spirometry, pain management, red blood cell transfusions, and exchange transfusions.
Overall Number of Participants Analyzed	4	3
Mean (Standard Deviation); Unit of Measure: hours
	279.43 (267.98)	127.31 (137.70)

2. Secondary Outcome

Title	Duration of Hypoxemia Assessed by Arterial Oxygen Saturation
Description	Arterial oxygen saturation less than 90%
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Unfractionated Heparin	Standard of Care
Arm/Group Description:	Subjects will be randomized within 24 hours of diagnosis to one of two treatment arms, Arm A, anticoagulation and standard of care, or Arm B, no anticoagulation and standard of care. Weight-adjusted UFH will be given at doses of 80 units per kilogram followed by 18 units per kilogram per hour intravenously for 7 days, or until discharge, if discharge is shorter than 7 days. UFH will be monitored by standard protocol to maintain the activated partial thromboplastin time in the therapeutic range per institutional guidelines. The experimental arm will receive standard of care, too, which will include the following: intravenous fluids, antibiotics, supplemental oxygen, incentive spirometry, pain management, red blood cell transfusions, and exchange transfusions. Unfractionated heparin	Standard care will include the following: intravenous fluids, antibiotics, supplemental oxygen, incentive spirometry, pain management, red blood cell transfusions, and exchange transfusions.
Overall Number of Participants Analyzed	4	3
Mean (Standard Deviation); Unit of Measure: hours
	117.62 (60.52)	51.49 (44.79)

3. Secondary Outcome

Title	Duration of Fever Assessed by Body Temperature
Description	Body temperature greater than or equal to 38.0 degrees Celsius
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Unfractionated Heparin	Standard of Care
Arm/Group Description:	Subjects will be randomized within 24 hours of diagnosis to one of two treatment arms, Arm A, anticoagulation and standard of care, or Arm B, no anticoagulation and standard of care. Weight-adjusted UFH will be given at doses of 80 units per kilogram followed by 18 units per kilogram per hour intravenously for 7 days, or until discharge, if discharge is shorter than 7 days. UFH will be monitored by standard protocol to maintain the activated partial thromboplastin time in the therapeutic range per institutional guidelines. The experimental arm will receive standard of care, too, which will include the following: intravenous fluids, antibiotics, supplemental oxygen, incentive spirometry, pain management, red blood cell transfusions, and exchange transfusions. Unfractionated heparin	Standard care will include the following: intravenous fluids, antibiotics, supplemental oxygen, incentive spirometry, pain management, red blood cell transfusions, and exchange transfusions.
Overall Number of Participants Analyzed	4	3
Mean (Standard Deviation); Unit of Measure: hours
	24.90 (29.69)	0 (0)

4. Secondary Outcome

Title	Duration of Leukocytosis Assessed by White Blood Cell Count
Description	White blood cell count greater than 10,000 per liter
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Unfractionated Heparin	Standard of Care
Arm/Group Description:	Subjects will be randomized within 24 hours of diagnosis to one of two treatment arms, Arm A, anticoagulation and standard of care, or Arm B, no anticoagulation and standard of care. Weight-adjusted UFH will be given at doses of 80 units per kilogram followed by 18 units per kilogram per hour intravenously for 7 days, or until discharge, if discharge is shorter than 7 days. UFH will be monitored by standard protocol to maintain the activated partial thromboplastin time in the therapeutic range per institutional guidelines. The experimental arm will receive standard of care, too, which will include the following: intravenous fluids, antibiotics, supplemental oxygen, incentive spirometry, pain management, red blood cell transfusions, and exchange transfusions. Unfractionated heparin	Standard care will include the following: intravenous fluids, antibiotics, supplemental oxygen, incentive spirometry, pain management, red blood cell transfusions, and exchange transfusions.
Overall Number of Participants Analyzed	4	3
Mean (Standard Deviation); Unit of Measure: hours
	117.52 (60.52)	53.11 (25.06)

5. Secondary Outcome

Title	Duration of Moderate to Severe Pain Assessed by Visual Analog Scale for Pain
Description	Score of 4 or greater on the Visual Analog Scale for pain
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Unfractionated Heparin	Standard of Care
Arm/Group Description:	Subjects will be randomized within 24 hours of diagnosis to one of two treatment arms, Arm A, anticoagulation and standard of care, or Arm B, no anticoagulation and standard of care. Weight-adjusted UFH will be given at doses of 80 units per kilogram followed by 18 units per kilogram per hour intravenously for 7 days, or until discharge, if discharge is shorter than 7 days. UFH will be monitored by standard protocol to maintain the activated partial thromboplastin time in the therapeutic range per institutional guidelines. The experimental arm will receive standard of care, too, which will include the following: intravenous fluids, antibiotics, supplemental oxygen, incentive spirometry, pain management, red blood cell transfusions, and exchange transfusions. Unfractionated heparin	Standard care will include the following: intravenous fluids, antibiotics, supplemental oxygen, incentive spirometry, pain management, red blood cell transfusions, and exchange transfusions.
Overall Number of Participants Analyzed	4	3
Mean (Standard Deviation); Unit of Measure: hours
	88.68 (72.77)	117.52 (60.52)

6. Secondary Outcome

Title	Opioid Administration Per Participant
Description	Total dose of opioids per participant
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Unfractionated Heparin	Standard of Care
Arm/Group Description:	Subjects will be randomized within 24 hours of diagnosis to one of two treatment arms, Arm A, anticoagulation and standard of care, or Arm B, no anticoagulation and standard of care. Weight-adjusted UFH will be given at doses of 80 units per kilogram followed by 18 units per kilogram per hour intravenously for 7 days, or until discharge, if discharge is shorter than 7 days. UFH will be monitored by standard protocol to maintain the activated partial thromboplastin time in the therapeutic range per institutional guidelines. The experimental arm will receive standard of care, too, which will include the following: intravenous fluids, antibiotics, supplemental oxygen, incentive spirometry, pain management, red blood cell transfusions, and exchange transfusions. Unfractionated heparin	Standard care will include the following: intravenous fluids, antibiotics, supplemental oxygen, incentive spirometry, pain management, red blood cell transfusions, and exchange transfusions.
Overall Number of Participants Analyzed	4	3
Mean (Standard Deviation); Unit of Measure: mg
	3,446.75 (4,465.93)	1,166.67 (1,112.61)

7. Secondary Outcome

Title	Units of Red Blood Cells Administered
Description	Total number of units of red blood cells
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Unfractionated Heparin	Standard of Care
Arm/Group Description:	Subjects will be randomized within 24 hours of diagnosis to one of two treatment arms, Arm A, anticoagulation and standard of care, or Arm B, no anticoagulation and standard of care. Weight-adjusted UFH will be given at doses of 80 units per kilogram followed by 18 units per kilogram per hour intravenously for 7 days, or until discharge, if discharge is shorter than 7 days. UFH will be monitored by standard protocol to maintain the activated partial thromboplastin time in the therapeutic range per institutional guidelines. The experimental arm will receive standard of care, too, which will include the following: intravenous fluids, antibiotics, supplemental oxygen, incentive spirometry, pain management, red blood cell transfusions, and exchange transfusions. Unfractionated heparin	Standard care will include the following: intravenous fluids, antibiotics, supplemental oxygen, incentive spirometry, pain management, red blood cell transfusions, and exchange transfusions.
Overall Number of Participants Analyzed	4	3
Measure Type: Number; Unit of Measure: units
	5	4

8. Secondary Outcome

Title	Percentage of Participants Transferred to Intensive Care Unit
Description	[Not Specified]
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Unfractionated Heparin	Standard of Care
Arm/Group Description:	Subjects will be randomized within 24 hours of diagnosis to one of two treatment arms, Arm A, anticoagulation and standard of care, or Arm B, no anticoagulation and standard of care. Weight-adjusted UFH will be given at doses of 80 units per kilogram followed by 18 units per kilogram per hour intravenously for 7 days, or until discharge, if discharge is shorter than 7 days. UFH will be monitored by standard protocol to maintain the activated partial thromboplastin time in the therapeutic range per institutional guidelines. The experimental arm will receive standard of care, too, which will include the following: intravenous fluids, antibiotics, supplemental oxygen, incentive spirometry, pain management, red blood cell transfusions, and exchange transfusions. Unfractionated heparin	Standard care will include the following: intravenous fluids, antibiotics, supplemental oxygen, incentive spirometry, pain management, red blood cell transfusions, and exchange transfusions.
Overall Number of Participants Analyzed	4	3
Measure Type: Number; Unit of Measure: percent of participants
	0	33

9. Secondary Outcome

Title	Percentage of Participants Requiring Mechanical Ventilation
Description	[Not Specified]
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Unfractionated Heparin	Standard of Care
Arm/Group Description:	Subjects will be randomized within 24 hours of diagnosis to one of two treatment arms, Arm A, anticoagulation and standard of care, or Arm B, no anticoagulation and standard of care. Weight-adjusted UFH will be given at doses of 80 units per kilogram followed by 18 units per kilogram per hour intravenously for 7 days, or until discharge, if discharge is shorter than 7 days. UFH will be monitored by standard protocol to maintain the activated partial thromboplastin time in the therapeutic range per institutional guidelines. The experimental arm will receive standard of care, too, which will include the following: intravenous fluids, antibiotics, supplemental oxygen, incentive spirometry, pain management, red blood cell transfusions, and exchange transfusions. Unfractionated heparin	Standard care will include the following: intravenous fluids, antibiotics, supplemental oxygen, incentive spirometry, pain management, red blood cell transfusions, and exchange transfusions.
Overall Number of Participants Analyzed	4	3
Measure Type: Number; Unit of Measure: percent of participants
	0	0

10. Secondary Outcome

Title	Percentage of Participants Experiencing Multiorgan Dysfunction Syndrome
Description	Acute development of 2 or more organs or organ systems unable to maintain homeostasis in a critically ill individual
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Unfractionated Heparin	Standard of Care
Arm/Group Description:	Subjects will be randomized within 24 hours of diagnosis to one of two treatment arms, Arm A, anticoagulation and standard of care, or Arm B, no anticoagulation and standard of care. Weight-adjusted UFH will be given at doses of 80 units per kilogram followed by 18 units per kilogram per hour intravenously for 7 days, or until discharge, if discharge is shorter than 7 days. UFH will be monitored by standard protocol to maintain the activated partial thromboplastin time in the therapeutic range per institutional guidelines. The experimental arm will receive standard of care, too, which will include the following: intravenous fluids, antibiotics, supplemental oxygen, incentive spirometry, pain management, red blood cell transfusions, and exchange transfusions. Unfractionated heparin	Standard care will include the following: intravenous fluids, antibiotics, supplemental oxygen, incentive spirometry, pain management, red blood cell transfusions, and exchange transfusions.
Overall Number of Participants Analyzed	4	3
Measure Type: Number; Unit of Measure: percent of participants
	0	0

Adverse Events

Time Frame	7 days
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Unfractionated Heparin		Standard of Care
Arm/Group Description	Subjects will be randomized within 24 hours of diagnosis to one of two treatment arms, Arm A, anticoagulation and standard of care, or Arm B, no anticoagulation and standard of care. Weight-adjusted UFH will be given at doses of 80 units per kilogram followed by 18 units per kilogram per hour intravenously for 7 days, or until discharge, if discharge is shorter than 7 days. UFH will be monitored by standard protocol to maintain the activated partial thromboplastin time in the therapeutic range per institutional guidelines. The experimental arm will receive standard of care, too, which will include the following: intravenous fluids, antibiotics, supplemental oxygen, incentive spirometry, pain management, red blood cell transfusions, and exchange transfusions. Unfractionated heparin		Standard care will include the following: intravenous fluids, antibiotics, supplemental oxygen, incentive spirometry, pain management, red blood cell transfusions, and exchange transfusions.
All-Cause Mortality
	Unfractionated Heparin		Standard of Care
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/4 (0.00%)		0/3 (0.00%)
Serious Adverse Events
	Unfractionated Heparin		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0.00%)		0/3 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Unfractionated Heparin		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/4 (25.00%)		0/3 (0.00%)
Blood and lymphatic system disorders
epistaxis *	1/4 (25.00%)	2	0/3 (0.00%)
* Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Craig Seaman, MD
• Organization: University of Pittsburgh
• Phone: 412-209-7308
• EMail: seamanc@upmc.edu

• Responsible Party: Craig Seaman, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT02098993
• Other Study ID Numbers: ACS13090197
• First Submitted: March 25, 2014
• First Posted: March 28, 2014
• Results First Submitted: May 28, 2019
• Results First Posted: July 16, 2019
• Last Update Posted: July 16, 2019