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

NCT00530270 | Terminated Phase 3 Results DMC

• 3 other identifiers: 516U54HL070587U54HL070587-07
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 6

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.

Conditions

Anemia, Sickle Cell

Keywords

Sickle Cell Disease; ACS; Acute Chest Syndrome; Hgb SS; Hgb Sβ0; Dexamethasone

Outcome Measures

Primary Outcomes (1)

• Log (Natural) of Duration of Signs and Symptoms of Acute Chest Syndrome (ACS) or Duration of Hospitalization, Whichever is Less

  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.

  Measured from first dose to end of the hospital stay, no maximum number of days

Secondary Outcomes (4)

• Rating of Pain

  Measured at the end of the hospital stay

• Duration of Hospitalization

  Measured at the end of hospital stay, no maximum number of days

• Duration of Supplemental Oxygen

  Measured at the end of hospital stay

• Duration of Hypoxemia (Low Blood Oxygen)

  Measured at the end of hospital stay

Study Arms (2)

Dexamethasone

ACTIVE COMPARATOR

Drug: Dexamethasone

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Dexamethasone DRUG

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.

Dexamethasone

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Temperature of 38.5°C or higher
• Tachypnea (i.e., rapid breathing)
• Dyspnea or increased work of breathing
• Chest wall pain
• 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

You may not qualify if:

• Prior participation in this study
• Diagnosed with any medical condition that will likely be worsened by corticosteroid therapy, including any of the following conditions:
• Diabetes mellitus
• High blood pressure
• Esophageal or gastrointestinal ulceration or bleeding
• 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

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (6)

University of California - Davis

Sacramento, California, 95817, United States

Location

Kosair Children's Hospital

Louisville, Kentucky, 40202, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

St. Christopher's Hospital

Philadelphia, Pennsylvania, 19134, United States

Location

Children's Medical Center of Dallas

Dallas, Texas, 75235, United States

Location

Related Publications (1)

• 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.

  PMID: 21848879 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell; Acute Chest Syndrome

Interventions

Dexamethasone

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Limitations and Caveats

Primary limitation of this study is that is was terminated prior to enrolling all of the subjects necessary to address the primary question.

Results Point of Contact

• Title: Karen Kesler, PhD
• Organization: Rho Federal Systems Division

karen_kesler@rhoworld.com

919-408-8000

Study Officials

• Charles Quinn, MD

  University of Texas, Southwestern Medical Center at Dallas

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 14, 2007
• First Posted: September 17, 2007
• Study Start: December 1, 2006
• Primary Completion: June 1, 2008
• Study Completion: November 1, 2008
• Last Updated: April 9, 2013
• Results First Posted: December 31, 2009

Record last verified: 2013-03

Locations

US (6)