Acute Chest Syndrome, Sickle Cell Disease
Conditions
Keywords
Sickle cell disease, Acute chest syndrome, Hemoglobinopathy, Hemolytic anemia, Heparin, Anticoagulant
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.
Interventions
DRUGUnfractionated heparin
Sponsors
Vascular Medicine Institute
Craig Seaman
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Hospital Discharge | Until hospital discharge | Duration of hospitalization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Fever Assessed by Body Temperature | 7 days | Body temperature greater than or equal to 38.0 degrees Celsius |
| Duration of Leukocytosis Assessed by White Blood Cell Count | 7 days | White blood cell count greater than 10,000 per liter |
| 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 |
| Opioid Administration Per Participant | 7 days | Total dose of opioids per participant |
| Duration of Hypoxemia Assessed by Arterial Oxygen Saturation | 7 days | Arterial oxygen saturation less than 90% |
| Percentage of Participants Transferred to Intensive Care Unit | 7 days | — |
| Percentage of Participants Requiring Mechanical Ventilation | 7 days | — |
| 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 |
| Units of Red Blood Cells Administered | 7 days | Total number of units of red blood cells |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Unfractionated heparin | 4 |
| 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. | 3 |
| Total | 7 |
Baseline characteristics
| Characteristic | Standard of Care | Total | Unfractionated Heparin |
|---|---|---|---|
| Age, Continuous | 32 years STANDARD_DEVIATION 18.52 | 30.43 years STANDARD_DEVIATION 11.12 | 29.25 years STANDARD_DEVIATION 3.77 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 7 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 3 |
| other Total, other adverse events | 1 / 4 | 0 / 3 |
| serious Total, serious adverse events | 0 / 4 | 0 / 3 |
Outcome results
Primary
Time to Hospital Discharge
Duration of hospitalization
Time frame: Until hospital discharge
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Unfractionated Heparin | Time to Hospital Discharge | 279.43 hours | Standard Deviation 267.98 |
| Standard of Care | Time to Hospital Discharge | 127.31 hours | Standard Deviation 137.7 |
Secondary
Duration of Fever Assessed by Body Temperature
Body temperature greater than or equal to 38.0 degrees Celsius
Time frame: 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Unfractionated Heparin | Duration of Fever Assessed by Body Temperature | 24.90 hours | Standard Deviation 29.69 |
| Standard of Care | Duration of Fever Assessed by Body Temperature | 0 hours | Standard Deviation 0 |
Secondary
Duration of Hypoxemia Assessed by Arterial Oxygen Saturation
Arterial oxygen saturation less than 90%
Time frame: 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Unfractionated Heparin | Duration of Hypoxemia Assessed by Arterial Oxygen Saturation | 117.62 hours | Standard Deviation 60.52 |
| Standard of Care | Duration of Hypoxemia Assessed by Arterial Oxygen Saturation | 51.49 hours | Standard Deviation 44.79 |
Secondary
Duration of Leukocytosis Assessed by White Blood Cell Count
White blood cell count greater than 10,000 per liter
Time frame: 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Unfractionated Heparin | Duration of Leukocytosis Assessed by White Blood Cell Count | 117.52 hours | Standard Deviation 60.52 |
| Standard of Care | Duration of Leukocytosis Assessed by White Blood Cell Count | 53.11 hours | Standard Deviation 25.06 |
Secondary
Duration of Moderate to Severe Pain Assessed by Visual Analog Scale for Pain
Score of 4 or greater on the Visual Analog Scale for pain
Time frame: 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Unfractionated Heparin | Duration of Moderate to Severe Pain Assessed by Visual Analog Scale for Pain | 88.68 hours | Standard Deviation 72.77 |
| Standard of Care | Duration of Moderate to Severe Pain Assessed by Visual Analog Scale for Pain | 117.52 hours | Standard Deviation 60.52 |
Secondary
Opioid Administration Per Participant
Total dose of opioids per participant
Time frame: 7 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Unfractionated Heparin | Opioid Administration Per Participant | 3,446.75 mg |
| Standard of Care | Opioid Administration Per Participant | 1,166.67 mg |
Secondary
Percentage of Participants Experiencing Multiorgan Dysfunction Syndrome
Acute development of 2 or more organs or organ systems unable to maintain homeostasis in a critically ill individual
Time frame: 7 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Unfractionated Heparin | Percentage of Participants Experiencing Multiorgan Dysfunction Syndrome | 0 percent of participants |
| Standard of Care | Percentage of Participants Experiencing Multiorgan Dysfunction Syndrome | 0 percent of participants |
Secondary
Percentage of Participants Requiring Mechanical Ventilation
Time frame: 7 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Unfractionated Heparin | Percentage of Participants Requiring Mechanical Ventilation | 0 percent of participants |
| Standard of Care | Percentage of Participants Requiring Mechanical Ventilation | 0 percent of participants |
Secondary
Percentage of Participants Transferred to Intensive Care Unit
Time frame: 7 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Unfractionated Heparin | Percentage of Participants Transferred to Intensive Care Unit | 0 percent of participants |
| Standard of Care | Percentage of Participants Transferred to Intensive Care Unit | 33 percent of participants |
Secondary
Units of Red Blood Cells Administered
Total number of units of red blood cells
Time frame: 7 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Unfractionated Heparin | Units of Red Blood Cells Administered | 5 units |
| Standard of Care | Units of Red Blood Cells Administered | 4 units |