Dexamethasone to Treat Acute Chest Syndrome in People With Sickle Cell Disease - Full Text View

Sponsored by:	National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:	National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:	NCT00530270

Purpose

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.

Condition	Intervention	Phase
Anemia, Sickle Cell	Drug: Dexamethasone Drug: Placebo	Phase III

Genetics Home Reference related topics: sickle cell disease

MedlinePlus related topics: Anemia Sickle Cell Anemia

Drug Information available for: Dexamethasone Dexamethasone acetate Dexamethasone Sodium Phosphate Doxiproct plus

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Randomized Trial of Oral Dexamethasone for Acute Chest Syndrome

Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:

Duration of signs and symptoms of ACS or duration of hospitalization, whichever is less [ Time Frame: Measured at the end of the hospital stay ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Rating of pain, duration of hospitalization, supplemental oxygen, hypoxemia, and fever [ Time Frame: Measured at the end of the hospital stay ] [ Designated as safety issue: Yes ]
Vascular cell adhesion molecule-1 (VCAM1), intercellular adhesion molecule-1 (ICAM1), P-selectin, L-selectin, von Willebrand factor (vWF) multimers, and endothelial and monocyte microparticles [ Time Frame: Measured at the end of the hospital stay ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: Yes ]
Whole blood tissue factor (WBTF), nitric oxide (NO), and secretory phospholipase A2 (sPLA2) [ Time Frame: Measured at the end of the hospital stay ] [ Designated as safety issue: No ]

Enrollment:	12
Study Start Date:	December 2006
Estimated Study Completion Date:	November 2008
Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Dexamethasone: Active Comparator	Drug: Dexamethasone Individuals meeting entry criteria will be randomized to receive either dexamethasone 0.3 mg/kg (12 mg maximum single dose) or an equivalent amount of placebo. The study drug will be given by mouth every 12 hours until discharge from the hospital or for a maximum of 4 doses (2 days), whichever occurs first. Thereafter, study drug will be tapered over 6 days for a total duration of therapy not to exceed 8 days.
Placebo: Placebo Comparator	Drug: Placebo Individuals meeting entry criteria will be randomized to receive either dexamethasone 0.3 mg/kg (12 mg maximum single dose) or an equivalent amount of placebo. The study drug will be given by mouth every 12 hours until discharge from the hospital or for a maximum of 4 doses (2 days), whichever occurs first. Thereafter, study drug will be tapered over 6 days for a total duration of therapy not to exceed 8 days.

Arms

Assigned Interventions

Dexamethasone: Active Comparator

Drug: Dexamethasone

Individuals meeting entry criteria will be randomized to receive either dexamethasone 0.3 mg/kg (12 mg maximum single dose) or an equivalent amount of placebo. The study drug will be given by mouth every 12 hours until discharge from the hospital or for a maximum of 4 doses (2 days), whichever occurs first. Thereafter, study drug will be tapered over 6 days for a total duration of therapy not to exceed 8 days.

Placebo: Placebo Comparator

Drug: Placebo

Individuals meeting entry criteria will be randomized to receive either dexamethasone 0.3 mg/kg (12 mg maximum single dose) or an equivalent amount of placebo. The study drug will be given by mouth every 12 hours until discharge from the hospital or for a maximum of 4 doses (2 days), whichever occurs first. Thereafter, study drug will be tapered over 6 days for a total duration of therapy not to exceed 8 days.

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

Ages Eligible for Study:	5 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00530270

Locations

United States, California
Children's Hospital and Research Center at Oakland
Oakland, California, United States, 94609
University of California - Davis
Sacramento, California, United States, 95817
University of Southern California
Los Angeles, California, United States, 90023
United States, Kentucky
Kosair Children's Hospital
Louisville, Kentucky, United States, 40202
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
United States, Oklahoma
University or Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
St. Christopher's Hospital
Philadelphia, Pennsylvania, United States, 19134
United States, Tennessee
St. Jude Children's Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
Children's Medical Center of Dallas
Dallas, Texas, United States, 75235

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator:

Charles Quinn, MD

University of Texas Southwestern Medical Center at Dallas

More Information

Responsible Party:	Universitry of Texas Southwestern Medical Center ( Charles Quinn, MD )
Study ID Numbers:	516, U54 HL070587-07
Study First Received:	September 14, 2007
Last Updated:	November 6, 2008
ClinicalTrials.gov Identifier:	NCT00530270
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):

Sickle Cell Disease
ACS
Acute Chest Syndrome

Hgb SS
Hgb Sβ0
Dexamethasone

Study placed in the following topic categories:

Dexamethasone
Anemia, Hemolytic, Congenital
Genetic Diseases, Inborn
Hematologic Diseases
Hemoglobinopathies
Anemia

Anemia, Hemolytic
Hemoglobinopathy
Anemia, Sickle Cell
Dexamethasone acetate
Sickle cell anemia

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Disease
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Gastrointestinal Agents
Antiemetics
Glucocorticoids

Hormones
Pharmacologic Actions
Pathologic Processes
Autonomic Agents
Syndrome
Therapeutic Uses
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009