Clinical trial NCT00530270: Dexamethasone to Treat Acute Chest Syndrome in People With Sickle Cell Disease
Official title: Randomized Trial of Oral Dexamethasone for Acute Chest Syndrome
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Anemia, Sickle Cell
Keywords: Sickle Cell Disease
ACS
Acute Chest Syndrome
Hgb SS
Hgb Sβ0
Dexamethasone
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2007-09-17
Enrollment: 12
Sex: ALL
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 description: 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 needed, a chest x-ray. Vital signs and blood pressure measurements will be taken every 4 hours. Study staff will document the amount of pain medication, blood transfusions, oxygen, and breathing treatments participants receive.

Upon leaving the hospital, follow-up visits will occur 1 week after participants were originally admitted to the hospital (participants who are still hospitalized at this time will not attend this visit) and 1 month after hospital discharge. At both visits, information on hospital visits for pain treatment and blood transfusions will be collected, and evaluations performed earlier in the study will be repeated. The second visit will also include lung function tests.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of sickle cell anemia (Hgb SS) or sickle-β0-thalassemia (Hgb Sβ0)
* Current episode of ACS, defined as a new lobar or segmental pulmonary infiltrate seen on a chest radiograph and two or more of the following findings:

  1. Temperature of 38.5°C or higher
  2. Tachypnea (i.e., rapid breathing)
  3. Dyspnea or increased work of breathing
  4. Chest wall pain
  5. Oxygen saturation of less than 90% in room air by pulse oximetry
* Current episode of ACS diagnosed in the 24 hours prior to study entry
* Ability to take medication in capsule form

Exclusion Criteria:

* Prior participation in this study
* Diagnosed with any medical condition that will likely be worsened by corticosteroid therapy, including any of the following conditions:

  1. Diabetes mellitus
  2. High blood pressure
  3. Esophageal or gastrointestinal ulceration or bleeding
  4. Known avascular necrosis
* Diagnosis of ACS in the 6 months prior to study entry
* Treatment with oral or parenteral corticosteroid therapy for any reason in the 14 days prior to study entry
* Use of inhaled corticosteroids or systemic corticosteroids for respiratory illness in the 3 months prior to study entry
* Long-term lung condition that requires treatment with corticosteroids
* Participation in a program of chronic transfusions that ended fewer than 4 months ago. A program of chronic transfusions includes a regimen of serial simple or exchange transfusions given at least every 6 weeks for at least three consecutive transfusions for the prevention of SCD-related complications.
* Pregnant
* Treatment with any investigational drug in the 90 days prior to study entry
* History of either tuberculosis or a positive skin test for tuberculosis
* Known HIV infection or a current systemic fungal infection

Primary outcomes:
measure: Log (Natural) of Duration of Signs and Symptoms of Acute Chest Syndrome (ACS) or Duration of Hospitalization, Whichever is Less
timeFrame: Measured from first dose to end of the hospital stay, no maximum number of days
Secondary outcomes:
measure: Rating of Pain
timeFrame: Measured at the end of the hospital stay
measure: Duration of Hospitalization
timeFrame: Measured at the end of hospital stay, no maximum number of days
measure: Duration of Supplemental Oxygen
timeFrame: Measured at the end of hospital stay
measure: Duration of Hypoxemia (Low Blood Oxygen)
timeFrame: Measured at the end of hospital stay
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California - Davis
state: California
city: Louisville
country: United States
facility: Kosair Children's Hospital
state: Kentucky
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Philadelphia
country: United States
facility: St. Christopher's Hospital
state: Pennsylvania
city: Dallas
country: United States
facility: Children's Medical Center of Dallas
state: Texas
Study officials:
affiliation: University of Texas, Southwestern Medical Center at Dallas
name: Charles Quinn, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Quinn CT, Stuart MJ, Kesler K, Ataga KI, Wang WC, Styles L, Smith-Whitley K, Wun T, Raj A, Hsu LL, Krishnan S, Kuypers FA, Setty Y, Rhee S, Key NS, Buchanan GR; Investigators of the Comprehensive Sickle Cell Centers. Tapered oral dexamethasone for the acute chest syndrome of sickle cell disease. Br J Haematol. 2011 Oct;155(2):263-7. doi: 10.1111/j.1365-2141.2011.08827.x. Epub 2011 Aug 16.