Preventing Acute Chest Syndrome by Transfusion Feasibility Study (PROACTIVE)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
New England Research Institutes
ClinicalTrials.gov Identifier:
NCT00951808
First received: July 31, 2009
Last updated: April 16, 2013
Last verified: April 2013

July 31, 2009
April 16, 2013
July 2009
June 2010   (final data collection date for primary outcome measure)
Acute Chest Syndrome [ Time Frame: 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. ] [ Designated as safety issue: No ]
First occurence of positive infiltrate on chest x-ray
Assess feasibility of conducting larger trial in terms of elapsed time between eligibility, randomization, transfusion, Assess number of CXR, number of patients who develop ACS and predictive value of elevated sPLA2 for predictive ACS. [ Time Frame: 13 months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00951808 on ClinicalTrials.gov Archive Site
Not Provided
Assess timely completion of all 3 sPLA2 for subjects with persistently low sPLA2 levels, % of screened subjects who are deemed eligible for randomization, % randomized, child/adult ratio, timing and results of sPLA2 samples. [ Time Frame: 13 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Preventing Acute Chest Syndrome by Transfusion Feasibility Study
Preventing Acute Chest Syndrome by Transfusion Feasibility Study( PROACTIVE Feasibility Study)

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.

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.

Interventional
Not Provided
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Sickle Cell Disease
  • Biological: Single blood transfusion
    Participants will receive a single transfusion of 7-13cc/kg packed red blood cells (RBCs) while in the hospital.
    Other Name: transfusion
  • Behavioral: Standard care
    Participants will receive standard care for ACS while in the hospital.
    Other Name: standard of care
  • Active Comparator: Blood Transfusion Trial Cohort
    Twenty participants will receive a blood transfusion while in the hospital.
    Intervention: Biological: Single blood transfusion
  • Active Comparator: Standard Care Trial Cohort
    Twenty participants will not receive a blood transfusion and will receive standard care.
    Intervention: Behavioral: Standard care
  • Active Comparator: Standard Care Observational Cohort
    Approximately 300 participants who are ineligible for or decline the blood transfusion part of the study will participate in the observational portion of the study and receive standard care.
    Intervention: Behavioral: Standard care

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
237
July 2010
June 2010   (final data collection date for primary outcome measure)

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-β thalassemia (β+ or β0)
  • 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
Both
2 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00951808
668, U10HL083721
Yes
New England Research Institutes
New England Research Institutes
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Sonja McKinlay, PhD New England Research Institutes
Study Director: Margaret C. Bell, MPH, MS New England Research Institutes
New England Research Institutes
April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP