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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
  Purpose

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.


Condition Intervention
Sickle Cell Disease
Biological: Single blood transfusion
Behavioral: Standard care

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Preventing Acute Chest Syndrome by Transfusion Feasibility Study( PROACTIVE Feasibility Study)

Resource links provided by NLM:


Further study details as provided by New England Research Institutes:

Primary Outcome Measures:
  • 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


Enrollment: 237
Study Start Date: July 2009
Study Completion Date: July 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Blood Transfusion Trial Cohort
Twenty participants will receive a blood transfusion while in the hospital.
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
Active Comparator: Standard Care Trial Cohort
Twenty participants will not receive a blood transfusion and will receive standard care.
Behavioral: Standard care
Participants will receive standard care for ACS while in the hospital.
Other Name: standard of 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.
Behavioral: Standard care
Participants will receive standard care for ACS while in the hospital.
Other Name: standard of care

Detailed 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.

  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00951808

  Show 24 Study Locations
Sponsors and Collaborators
New England Research Institutes
Investigators
Principal Investigator: Sonja McKinlay, PhD New England Research Institutes
Study Director: Margaret C. Bell, MPH, MS New England Research Institutes
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: New England Research Institutes
ClinicalTrials.gov Identifier: NCT00951808     History of Changes
Other Study ID Numbers: 668, U10HL083721
Study First Received: July 31, 2009
Results First Received: April 25, 2012
Last Updated: April 16, 2013
Health Authority: United States: Federal Government

Keywords provided by New England Research Institutes:
Anemia, Sickle Cell
Acute Chest Syndrome
Secretory phospholipase A2(sPLA2)

Additional relevant MeSH terms:
Acute Chest Syndrome
Anemia, Sickle Cell
Syndrome
Anemia
Anemia, Hemolytic
Anemia, Hemolytic, Congenital
Disease
Genetic Diseases, Inborn
Hematologic Diseases
Hemoglobinopathies
Lung Diseases
Pathologic Processes
Respiration Disorders
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on November 20, 2014