Feasibility Study of Unfractionated Heparin in Acute Chest Syndrome

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

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.

Study Overview

• Status: Terminated
• Conditions: Sickle Cell Disease; Acute Chest Syndrome
• Intervention / Treatment: Drug: Unfractionated heparin

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburg Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Craig Seaman
• Collaborators: Vascular Medicine Institute
• Investigators: Principal Investigator: Craig D Seaman, MD, University of Pittsburgh; Principal Investigator: Margaret Ragni, MD, MPH, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): June 27, 2018
• Study Completion (Actual): June 27, 2018

Study Registration Dates

• First Submitted: March 25, 2014
• First Submitted That Met QC Criteria: March 25, 2014
• First Posted (Estimate): March 28, 2014

Study Record Updates

• Last Update Posted (Actual): July 16, 2019
• Last Update Submitted That Met QC Criteria: June 25, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Heparin; Sickle cell disease; Anticoagulant; Hemoglobinopathy; Acute chest syndrome; Hemolytic anemia
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Syndrome; Anemia, Sickle Cell; Acute Chest Syndrome; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin; Calcium heparin
• Other Study ID Numbers: ACS13090197

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No