Feasibility Study of Unfractionated Heparin in Acute Chest Syndrome

Study Overview
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Brief Summary
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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.

Official Title
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Unfractionated Heparin in Acute Chest Syndrome: A Pilot Feasibility Randomized Controlled Trial of Unfractionated Heparin vs. Standard of Care in Acute Chest Syndrome

Conditions
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Acute Chest Syndrome, Sickle Cell Disease

Intervention / Treatment
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* Drug: Unfractionated heparin


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Hospital Discharge | Duration of hospitalization | Until hospital discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Hypoxemia Assessed by Arterial Oxygen Saturation | Arterial oxygen saturation less than 90% | 7 days | 
| Duration of Fever Assessed by Body Temperature | Body temperature greater than or equal to 38.0 degrees Celsius | 7 days | 
| Duration of Leukocytosis Assessed by White Blood Cell Count | White blood cell count greater than 10,000 per liter | 7 days | 
| 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 | 7 days | 
| Opioid Administration Per Participant | Total dose of opioids per participant | 7 days | 
| Units of Red Blood Cells Administered | Total number of units of red blood cells | 7 days | 
| 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 | Acute development of 2 or more organs or organ systems unable to maintain homeostasis in a critically ill individual | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sickle cell disease, Acute chest syndrome, Hemoglobinopathy, Hemolytic anemia, Heparin, Anticoagulant