Feasibility Study of Unfractionated Heparin in Acute Chest Syndrome

Phase 2

Terminated

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.

Recruitment & Eligibility

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)

Arm && Interventions

Group	Intervention	Description
Unfractionated heparin	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.

Primary Outcome Measures

Name	Time	Method
Time to Hospital Discharge	Until hospital discharge	Duration of hospitalization

Secondary Outcome Measures

Name	Time	Method
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
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
Units of Red Blood Cells Administered	7 days	Total number of units of red blood cells
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