Clinical Trial: Dexamethasone to Treat Acute Chest Syndrome in People With Sickle Cell Disease

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Randomized Trial of Oral Dexamethasone for Acute Chest Syndrome

Brief Summary: People with sickle cell disease (SCD) may develop acute chest syndrome (ACS), which is a common and serious lung condition that usually requires hospitalization. Dexamethasone is a medication that may decrease hospitalization time for people with ACS, but it may also bring about new sickle cell pain. This study will evaluate the effectiveness of a dexamethasone regimen that includes a gradual dose reduction at decreasing hospitalization and recovery time in people with SCD and ACS.

Detailed Summary:

SCD is an inherited blood disorder. Symptoms include anemia, infections, organ damage, and intense episodes of pain, which are called "sickle cell crises." ACS is a life-threatening, lung-related complication of SCD that can lower the level of oxygen in the blood. Repeat occurrences of ACS can cause lung damage. It is the second most common cause of hospitalizations among people with SCD and accounts for more than 25% of premature deaths in people with SCD. Symptoms of ACS include fever, chest pain, cough, and breathing difficulties. ACS can appear suddenly and often requires immediate hospitalization and treatment, including antibiotics, supplemental oxygen, and blood transfusions. Previous studies have shown that dexamethasone, a type of steroid medication that blocks inflammation, can decrease hospitalization time for people with ACS; however, some participants in these earlier studies were re-hospitalized due to new sickle cell pain. Slowly decreasing the dosage of dexamethasone over a period of time may decrease the chance that new sickle cell pain will occur. The purpose of this study is to evaluate the effectiveness of a dexamethasone regimen that includes a gradual dose reduction at decreasing hospitalization and recovery time in people with SCD and ACS.

This study will enroll people with SCD who are hospitalized and have been diagnosed with ACS within the past 24 hours. Participants will be randomly assigned to receive either dexamethasone or placebo on a daily basis for 8 days. Every 2 days the medication dose will be gradually reduced. While in the hospital, participants will receive usual care for ACS, including antibiotics, pain control medication, intravenous fluids, and other needed treatments. Each day, participants will undergo a physical exam, a pain assessment score, a test to measure the oxygen level in the body, blood collection, and, if nee
Sponsor: Children's Hospital Medical Center, Cincinnati

Current Primary Outcome: Log (Natural) of Duration of Signs and Symptoms of Acute Chest Syndrome (ACS) or Duration of Hospitalization, Whichever is Less [ Time Frame: Measured from first dose to end of the hospital stay, no maximum number of days ]

Resolution of symptoms of ACS includes respiratory rate <= upper limit of normal +2, no work of breathing (retractions, nasal flaring, and use of accessory muscles), thoracic pain <= 4, no use of supplemental oxygen, no use of ventilary support, and saturation of peripheral oxygen (Sp02) >= steady state value -2. Symptoms were measured every 4 hours from the first dose of study drug to resolution of symptoms or hospital discharge.


Original Primary Outcome: Duration of signs and symptoms of ACS or duration of hospitalization, whichever is less [ Time Frame: Measured at the end of the hospital stay ]

Current Secondary Outcome:

  • Rating of Pain [ Time Frame: Measured at the end of the hospital stay ]
    Change from baseline rating of pain from randomization (baseline) to discharge from the hospital, evaluated every 4 hours. Pain was rated on the Oucher Scale for the pediatric population or numeric rating scale for the adult population, both 0 to 10 with 0 indicating no pain and 10 indicating severe pain.
  • Duration of Hospitalization [ Time Frame: Measured at the end of hospital stay, no maximum number of days ]
    Duration in hours from treatment start time to hospital discharge.
  • Duration of Supplemental Oxygen [ Time Frame: Measured at the end of hospital stay ]
    Time period between the supplemental oxygen start date/time and first dose date/time, whichever is later, and the supplemental oxygen stop date/time
  • Duration of Hypoxemia (Low Blood Oxygen) [ Time Frame: Measured at the end of hospital stay ]
    Sum of time periods when subject was hypoxemic (Sp02 value less than 92%) since the first dose date/time


Original Secondary Outcome:

  • Rating of pain, duration of hospitalization, supplemental oxygen, hypoxemia, and fever [ Time Frame: Measured at the end of the hospital stay ]
  • Vascular cell adhesion molecule-1 (VCAM1), intercellular adhesion molecule-1 (ICAM1), Pselectin, L-selectin, von Willebrand factor (vWF) multimers, and endothelial and monocyte microparticles [ Time Frame: Measured at the end of the hospital stay ]
  • Number of transfusions, quantification of opioid use, rebound hospitalizations, pulmonary radiographic findings, and pulmonary function test results [ Time Frame: Measured at the end of the hospital stay ]
  • Whole blood tissue factor (WBTF), nitric oxide (NO), and secretory phospholipase A2 (sPLA2) [ Time Frame: Measured at the end of the hospital stay ]


Information By: Children's Hospital Medical Center, Cincinnati

Dates:
Date Received: September 14, 2007
Date Started: December 2006
Date Completion:
Last Updated: March 29, 2013
Last Verified: March 2013