Preventing Acute Chest Syndrome by Transfusion Feasibility Study

Sickle Cell Disease Clinical Trial

— PROACTIVE  

Official title:

Preventing Acute Chest Syndrome by Transfusion Feasibility Study( PROACTIVE Feasibility Study)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00951808
• Other study ID #: 668
• Secondary ID: U10HL083721
• Status: Completed
• Phase: N/A
• First received: July 31, 2009
• Last updated: April 16, 2013
• Start date: July 2009
• Est. completion date: July 2010

Study information

• Verified date: April 2013
• Source: New England Research Institutes
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

Acute chest syndrome (ACS) is similar to severe pneumonia and is a common cause of hospitalizations for people with sickle cell disease (SCD). Blood transfusions are one treatment option for ACS. High levels of an enzyme called secretory phospholipase A2 (sPLA2) may be present in people before they develop ACS. This study will determine how well sPLA2 levels can predict the onset of ACS and whether identifying high sPLA2 levels allows enough time to prevent ACS with blood transfusions. Results from this study will help to determine the feasibility of conducting a larger study that would further examine the use of sPLA2 levels and blood transfusions to prevent ACS in people with SCD.

Description:

SCD is an inherited blood disorder, and symptoms include anemia, infections, organ damage, and intense episodes of pain, which are called "sickle cell crises." ACS, characterized by fever, respiratory distress, and lung tissue damage, is the second most common cause of hospitalization and the leading cause of death among people with SCD. Most people with SCD will experience at least one episode of ACS, and repeated episodes can result in progressive lung disease. ACS can appear suddenly and often requires immediate hospitalization and treatment, which can include blood transfusions. People with elevated blood levels of sPLA2 may be at risk for developing ACS, and this enzyme is often detectable before the onset of ACS symptoms. The purpose of this study is to examine the use of sPLA2 as a predictor of ACS and to determine whether subsequent blood transfusions can be administered early enough to prevent the onset of ACS in people with SCD who are at risk for ACS. Study researchers will also assess the feasibility of conducting a larger study that would further examine the effectiveness of using sPLA2 levels and blood transfusions to prevent ACS.

This study will involve two parts. In the first part of the study, participants with SCD who are admitted to the hospital with an acute sickle cell pain event will be randomly assigned to receive either a single blood transfusion or standard care for ACS and no blood transfusion. All participants will be closely monitored while in the hospital for the development of ACS, and study researchers will review participants' medical records. All participants will undergo daily blood collections, which will include testing for sPLA2 levels, and at least two chest x-rays. Twenty-eight days after hospital discharge, all participants will attend a follow-up study visit for blood collection, again to determine sPLA2 levels.

In the second part of the study, participants who are not eligible or who do not choose to participate in the first part of the study will be enrolled into an observational group. These participants will receive standard care for ACS, but will not receive a blood transfusion. They will undergo daily blood collection during their hospital stay and at least one chest x-ray. While participants are in the hospital and 28 days after discharge, study researchers will review participants' medical records.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 237
• Est. completion date: July 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years and older

Eligibility

Inclusion Criteria for the Observational and Trial Cohorts:

• Hemoglobin diagnosis of SS (two copies of the hemoglobin S gene), SC (one copy of the hemoglobin S gene and one copy of the hemoglobin C gene), or S-ß thalassemia (ß+ or ß0)

• No clinically apparent ACS

• No prior participation in either part of the study

Inclusion Criteria for the Trial Cohort, in addition to the above criteria:

• sPLA2 level greater than 100 ng/mL within the same 24-hour window that coincides with fever and chest radiograph negative for new pulmonary infiltrate within the last 12 hours of the 24-hour window

• Fever greater than 38.0º C within the same 24-hour window that coincides with elevated sPLA2 level (greater than 100 ng/mL) and chest radiograph negative for new pulmonary infiltrate within the last 12 hours of the 24-hour window

• Chest radiograph negative for new pulmonary infiltrate within the last 12 hours of the 24-hour window of an abnormal sPLA2 level and fever

• Hemoglobin levels equal or less than 10 g/dL at time of study entry

• Informed consent of parent(s) or legal guardian; informed consent or assent of participant as applicable

Exclusion Criteria for Observational and Trial Cohorts:

• Existing diagnosis of a new pulmonary infiltrate diagnosed by chest radiography (pleural effusion not obscuring lung parenchyma will not exclude the person from the study)

• Any coexisting medical condition for which the physician feels that a transfusion may be needed within 24 hours (e.g., severe anemia, stroke)

• Red Blood Cell (RBC) transfusion in the 60 days before study entry

• Unwillingness to sign consent form, or if a minor, unwillingness of parent/guardian to sign consent form

• Treatment with any investigational drug or device in the 30 days before study entry (hydroxyurea is allowable)

• History of alloimmunization that would prevent the participant from receiving blood within 8 hours of eligibility for study entry or history of a life-threatening transfusion reaction

• Objection to transfusion for religious or other reasons from either the participant or guardian

• History of treatment with systemic steroids within 1 week of study entry (inhaled steroids are acceptable)

• Pregnant

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Chest Syndrome
• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

Biological:
• Single blood transfusion
Participants will receive a single transfusion of 7-13cc/kg packed red blood cells (RBCs) while in the hospital.

Behavioral:
• Standard care
Participants will receive standard care for ACS while in the hospital.

Locations

Country	Name	City	State
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Medical College of Georgia	Augusta	Georgia
United States	Johns Hopkins	Baltimore	Maryland
United States	Children's Hospital Boston	Boston	Massachusetts
United States	Boston Medical Center	Boston,	Massachusetts
United States	Brigham & Women's Hospital	Boston,	Massachusetts
United States	Interfaith Medical Center	Brooklyn	New York
United States	New York Methodist Hospital	Brooklyn	New York
United States	The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Children's Memorial Hospital	Chicago	Illinois
United States	University of Illinois Sickle Cell Center	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Ohio State University	Columbus	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Kosair Children's Hospital	Louisville	Kentucky
United States	Children's Hospital and Research Center	Oakland	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	Virginia Commonwealth University Health Systems	Richmond	Virginia
United States	Children's National Medical Center	Washington	District of Columbia
United States	Howard University Hospital	Washington	District of Columbia
United States	A.I. duPont Hospital for Children	Wilmington	Delaware

Sponsors (2)

Lead Sponsor	Collaborator
New England Research Institutes	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (2)

Miller ST, Kim HY, Weiner D, Wager CG, Gallagher D, Styles L, Dampier CD; Investigators of the Sickle Cell Disease Clinical Research Network (SCDCRN). Inpatient management of sickle cell pain: a 'snapshot' of current practice. Am J Hematol. 2012 Mar;87(3) — View Citation

Styles L, Wager CG, Labotka RJ, Smith-Whitley K, Thompson AA, Lane PA, McMahon LE, Miller R, Roseff SD, Iyer RV, Hsu LL, Castro OL, Ataga KI, Onyekwere O, Okam M, Bellevue R, Miller ST; Sickle Cell Disease Clinical Research Network (SCDCRN). Refining the — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Acute Chest Syndrome	First occurence of positive infiltrate on chest x-ray	Chest x-rays (CXR) were ordered for trial eligibility, as a result of clinical indications, or at discharge or 72 hours if no prior CXR.	No