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

This study has been terminated.
(Study was closed June 23, 2008 due to low enrollment.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Dr. Charles Quinn, Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier:
NCT00530270
First received: September 14, 2007
Last updated: March 29, 2013
Last verified: March 2013
  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 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized Trial of Oral Dexamethasone for Acute Chest Syndrome

Resource links provided by NLM:


Further study details as provided by Children's Hospital Medical Center, Cincinnati:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Rating of Pain [ Time Frame: Measured at the end of the hospital stay ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    Duration in hours from treatment start time to hospital discharge.

  • Duration of Supplemental Oxygen [ Time Frame: Measured at the end of hospital stay ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Sum of time periods when subject was hypoxemic (Sp02 value less than 92%) since the first dose date/time


Enrollment: 12
Study Start Date: December 2006
Study Completion Date: November 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Dexamethasone Drug: Dexamethasone
Individuals meeting entry criteria will be randomized to receive dexamethasone 0.3 mg/kg (12 mg maximum single dose). 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 Comparator: Placebo Drug: Placebo
Individuals meeting entry criteria will be randomized to receive 0.3 mg/kg (12 mg maximum single dose) 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, California
University of California - Davis
Sacramento, California, United States, 95817
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, Pennsylvania
St. Christopher's Hospital
Philadelphia, Pennsylvania, United States, 19134
United States, Texas
Children's Medical Center of Dallas
Dallas, Texas, United States, 75235
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Investigators
Principal Investigator: Charles Quinn, MD University of Texas Southwestern Medical Center at Dallas
  More Information

No publications provided by Children's Hospital Medical Center, Cincinnati

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr. Charles Quinn, Associate Professor, Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT00530270     History of Changes
Other Study ID Numbers: 516, U54HL070587, U54 HL070587-07
Study First Received: September 14, 2007
Results First Received: July 16, 2009
Last Updated: March 29, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Hospital Medical Center, Cincinnati:
Sickle Cell Disease
ACS
Acute Chest Syndrome
Hgb SS
Hgb Sβ0
Dexamethasone

Additional relevant MeSH terms:
Anemia
Anemia, Sickle Cell
Acute Chest Syndrome
Hematologic Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hemoglobinopathies
Genetic Diseases, Inborn
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014