Feasibility Study of Unfractionated Heparin in Acute Chest Syndrome

• Sponsor: Craig Seaman (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02098993
• Collaborator: Vascular Medicine Institute (Other)
• Enrollment: 7
• Location: 1
• Arms: 2
• Duration (Months): 49.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the feasibility of performing a larger multicenter phase III trial to assess the effects of unfractionated heparin (UFH) in acute chest syndrome (ACS). Prespecified feasibility criteria consists of the ability to enroll potential study participants, which includes the timely notification of hospitalized patients with ACS, the capacity to consent eligible individuals, and the ability to appropriately randomize eligible patients within 24 hours of diagnosis. Additional feasibility objectives involve ensuring appropriate eligibility criteria, proper administration of the study drug, and the ability to completely and accurately collect clinical data of interest. The final aim of our pilot study is to provide preliminary data, with respect to treatment effect and variance, to allow sample size calculation in a larger trial given the lack of data available to help guide this process. The investigators hypothesize that the use of UFH in ACS will result in a decrease in the duration of hospitalization and improve other clinical outcomes, such as the duration of hypoxemia and duration of moderate to severe pain.

Condition or Disease	Intervention/Treatment	Phase
Acute Chest Syndrome; Sickle Cell Disease	Drug: Unfractionated heparin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Unfractionated Heparin in Acute Chest Syndrome: A Pilot Feasibility Randomized Controlled Trial of Unfractionated Heparin vs. Standard of Care in Acute Chest Syndrome
• Study Start Date: May 1, 2014
• Actual Primary Completion Date: Jun 27, 2018
• Actual Study Completion Date: Jun 27, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Unfractionated heparin 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.	Drug: Unfractionated heparin
No Intervention: Standard of care Standard care will include the following: intravenous fluids, antibiotics, supplemental oxygen, incentive spirometry, pain management, red blood cell transfusions, and exchange transfusions.

Outcome Measures

Primary Outcome Measures

1. Time to Hospital Discharge [Until hospital discharge]

   Duration of hospitalization

Secondary Outcome Measures

1. Duration of Hypoxemia Assessed by Arterial Oxygen Saturation [7 days]

   Arterial oxygen saturation less than 90%

2. Duration of Fever Assessed by Body Temperature [7 days]

   Body temperature greater than or equal to 38.0 degrees Celsius

3. Duration of Leukocytosis Assessed by White Blood Cell Count [7 days]

   White blood cell count greater than 10,000 per liter

4. Duration of Moderate to Severe Pain Assessed by Visual Analog Scale for Pain [7 days]

   Score of 4 or greater on the Visual Analog Scale for pain

5. Opioid Administration Per Participant [7 days]

   Total dose of opioids per participant

6. Units of Red Blood Cells Administered [7 days]

   Total number of units of red blood cells

7. Percentage of Participants Transferred to Intensive Care Unit [7 days]

8. Percentage of Participants Requiring Mechanical Ventilation [7 days]

9. Percentage of Participants Experiencing Multiorgan Dysfunction Syndrome [7 days]

   Acute development of 2 or more organs or organ systems unable to maintain homeostasis in a critically ill individual

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of ACS defined as a new pulmonary infiltrate involving at least one segment of the lung on a chest x-ray or chest CT scan with 2 or more of the following: chest pain, tachypnea, dyspnea, cough, hypoxemia, or body temperature greater than or equal to 38.0 degrees Celsius

• Hemoglobin electrophoresis confirming HbSS, SC, or B0 (historical records sufficient)

• Age greater than or equal to 18

Exclusion Criteria:

• Any absolute contraindication to heparin

• Platelet count less than 50 per microliter (current admission)

• Historical diagnosis of moyamoya disease as documented in medical records

• Historical diagnosis of proliferative retinopathy as documented in medical records

• Current participation in a chronic exchange transfusion program

• Underlying hypercoagulable disorder other than sickle cell disease

• Currently receiving therappeutic anticoagulation

• Currently receiving antiplatelet agents

• Currently receiving estrogen containing oral contraceptives

• Chest CT scan documented PE performed as standard of care prior to study enrollment (current admission)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pittsburg Medical Center	Pittsburgh	Pennsylvania	United States	15213

Sponsors and Collaborators

• Craig Seaman
• Vascular Medicine Institute

Investigators

• Principal Investigator: Craig D Seaman, MD, University of Pittsburgh
• Principal Investigator: Margaret Ragni, MD, MPH, University of Pittsburgh

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 8, 2018

More Information

Publications

None provided.

• Responsible Party: Craig Seaman, Assistant Professor of Medicine, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT02098993
• Other Study ID Numbers: ACS13090197
• First Posted: Mar 28, 2014
• Last Update Posted: Jul 16, 2019
• Last Verified: Jun 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Craig Seaman, Assistant Professor of Medicine, University of Pittsburgh: Sickle cell disease; Acute chest syndrome; Hemoglobinopathy; Hemolytic anemia; Heparin; Anticoagulant
• Additional relevant MeSH terms: Acute Chest Syndrome; Anemia, Sickle Cell; Syndrome; Heparin; Calcium heparin

Study Results

Participant Flow

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 Participants	4	3	7
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	29.25 (3.77)	32 (18.52)	30.43 (11.12)
Sex: Female, Male (Count of Participants)
Female	2 50%	2 66.7%	4 57.1%
Male	2 50%	1 33.3%	3 42.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	4 100%	3 100%	7 100%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	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.
Measure Participants	4	3
Mean (Standard Deviation) [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.
Measure Participants	4	3
Mean (Standard Deviation) [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.
Measure Participants	4	3
Mean (Standard Deviation) [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.
Measure Participants	4	3
Mean (Standard Deviation) [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.
Measure Participants	4	3
Mean (Standard Deviation) [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.
Measure Participants	4	3
Mean (Standard Deviation) [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.
Measure Participants	4	3
Number [units]	5	4

8. Secondary Outcome

Title	Percentage of Participants Transferred to Intensive Care Unit
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.
Measure Participants	4	3
Number [percent of participants]	0 0%	33 1100%

9. Secondary Outcome

Title	Percentage of Participants Requiring Mechanical Ventilation
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.
Measure Participants	4	3
Number [percent of participants]	0 0%	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.
Measure Participants	4	3
Number [percent of participants]	0 0%	0 0%

Adverse Events

Time Frame	7 days
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/3 (0%)
Serious Adverse Events
	Unfractionated Heparin		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	Unfractionated Heparin		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/4 (25%)		0/3 (0%)
Blood and lymphatic system disorders
epistaxis	1/4 (25%)	2	0/3 (0%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.