Sickle Cell DiseasePROACTIVENCT00951808
Preventing Acute Chest Syndrome by Transfusion Feasibility Study
A study testing Single blood transfusion in people with Sickle Cell Disease, run by Carelon Research at 24 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Single blood transfusion
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 237 participants
- Where
- 24 sitesUnited States
- Study dates
- Jul 2009to Jul 2010
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
24 sites in 1 country.
24 sites in 1 country
United States24 sites
Emory University School of Medicine
Atlanta, Georgia
Medical College of Georgia
Augusta, Georgia
Johns Hopkins
Baltimore, Maryland
Boston Medical Center
Boston, Massachusetts
Brigham & Women's Hospital
Boston, Massachusetts
Children's Hospital Boston
Boston, Massachusetts
Interfaith Medical Center
Brooklyn, New York
New York Methodist Hospital
Brooklyn, New York
The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina
Children's Memorial Hospital
Chicago, Illinois
University of Illinois Sickle Cell Center
Chicago, Illinois
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio
Nationwide Children's Hospital
Columbus, Ohio
Ohio State University
Columbus, Ohio
Duke University Medical Center
Durham, North Carolina
University of Mississippi Medical Center
Jackson, Mississippi
Kosair Children's Hospital
Louisville, Kentucky
Children's Hospital and Research Center
Oakland, California
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania
St. Christopher's Hospital for Children
Philadelphia, Pennsylvania
Virginia Commonwealth University Health Systems
Richmond, Virginia
Children's National Medical Center
Washington D.C., District of Columbia
Howard University Hospital
Washington D.C., District of Columbia
A.I. duPont Hospital for Children
Wilmington, Delaware
About this study
Official title: 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.
Read the 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.
- Conditions
- Sickle Cell Disease
- Being tested
- Single blood transfusion, Standard care
- Keywords
- Anemia, Sickle Cell, Acute Chest Syndrome, Secretory phospholipase A2(sPLA2)
- Medical subject headings
- Anemia, Sickle Cell, Acute Chest Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Single blood transfusionBiological
Also called transfusion
Participants will receive a single transfusion of 7-13cc/kg packed red blood cells (RBCs) while in the hospital.
Standard careBehavioural
Also called standard of care
Participants will receive standard care for ACS while in the hospital.
| Study group | Role | What they receive |
|---|---|---|
| Blood Transfusion Trial Cohort | Active comparator | Twenty participants will receive a blood transfusion while in the hospital. Receives: Biological: Single blood transfusion |
| Standard Care Trial Cohort | Active comparator | Twenty participants will not receive a blood transfusion and will receive standard care. Receives: Behavioral: Standard care |
| Standard Care Observational Cohort | Active comparator | 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. Receives: Behavioral: Standard care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Acute Chest Syndrome
First occurence of positive infiltrate on chest x-ray
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2009 (estimated)
- Study startJul 2009
- Primary completionJun 2010
- Study completionJul 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 237 participants (actual)
Sponsor and investigators
- Lead sponsor
- Carelon Research
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Sonja McKinlay, PhD, Principal investigator, Carelon ResearchMargaret C. Bell, MPH, MS, Study director, Carelon Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00951808
- Sponsor's protocol ID
- 668
- Other IDs
- U10HL083721
- Acronym
- PROACTIVE
- Status last verified
- Apr 2013
- First submitted
- 31 Jul 2009
- Last updated
- 24 Apr 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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):333-6. doi: 10.1002/ajh.22265. Epub 2012 Jan 9.
PubMed 22231150Styles 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 value of secretory phospholipase A2 as a predictor of acute chest syndrome in sickle cell disease: results of a feasibility study (PROACTIVE). Br J Haematol. 2012 Jun;157(5):627-36. doi: 10.1111/j.1365-2141.2012.09105.x. Epub 2012 Mar 30.
PubMed 22463614Miller ST, Kim HY, Weiner DL, Wager CG, Gallagher D, Styles LA, Dampier CD, Roseff SD; Investigators of the Sickle Cell Disease Clinical Research Network (SCDCRN). Red blood cell alloimmunization in sickle cell disease: prevalence in 2010. Transfusion. 2013 Apr;53(4):704-9. doi: 10.1111/j.1537-2995.2012.03796.x. Epub 2012 Jul 13.
PubMed 22804353
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preventing Acute Chest Syndrome by Transfusion Feasibility Study( PROACTIVE Feasibility Study)
- ClinicalTrials.gov ID
- NCT00951808
- Acronym / sponsor ID
- PROACTIVE / 668
- Conditions
- Sickle Cell Disease
- Keywords
- Anemia, Sickle Cell, Acute Chest Syndrome, Secretory phospholipase A2(sPLA2)
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 237 participants (actual)
- Lead sponsor
- Carelon ResearchUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Jul 2009
- Primary completion
- Jun 2010 (actual)
- Study completion
- Jul 2010 (actual)
- First posted
- 4 Aug 2009 (estimated)
- Results
- Posted 5 Apr 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Blood Transfusion Trial Cohort | Active comparator | Biological: Single blood transfusionTwenty participants will receive a blood transfusion while in the hospital. |
| Standard Care Trial Cohort | Active comparator | Behavioral: Standard careTwenty participants will not receive a blood transfusion and will receive standard care. |
| Standard Care Observational Cohort | Active comparator | Behavioral: Standard careApproximately 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. |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- 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
- 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
Key exclusion criteria (9 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Single blood transfusionAlso: transfusionParticipants will receive a single transfusion of 7-13cc/kg packed red blood cells (RBCs) while in the hospital. | Biological | Blood Transfusion Trial Cohort |
| Standard careAlso: standard of careParticipants will receive standard care for ACS while in the hospital. | Behavioural | Standard Care Observational Cohort, Standard Care Trial Cohort |
Primary outcome
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.
First occurence of positive infiltrate on chest x-ray
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22231150Miller 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):333-6. doi: 10.1002/ajh.22265. Epub 2012 Jan 9.
- Results publication: PubMed 22463614Styles 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 value of secretory phospholipase A2 as a predictor of acute chest syndrome in sickle cell disease: results of a feasibility study (PROACTIVE). Br J Haematol. 2012 Jun;157(5):627-36. doi: 10.1111/j.1365-2141.2012.09105.x. Epub 2012 Mar 30.
- Derived from this study: PubMed 22804353Miller ST, Kim HY, Weiner DL, Wager CG, Gallagher D, Styles LA, Dampier CD, Roseff SD; Investigators of the Sickle Cell Disease Clinical Research Network (SCDCRN). Red blood cell alloimmunization in sickle cell disease: prevalence in 2010. Transfusion. 2013 Apr;53(4):704-9. doi: 10.1111/j.1537-2995.2012.03796.x. Epub 2012 Jul 13.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sonja McKinlay, PhD principal investigator
Carelon Research
Margaret C. Bell, MPH, MS study director
Carelon Research
24 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Single blood transfusion in people with Sickle Cell Disease, run by Carelon Research at 24 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Apr 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00951808, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2013; AzTrials last refreshed its copy on 1 Nov 2026.