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A Pilot Study of Chronic Red Blood Cell Transfusion in Sickle Cell Disease-Associated Pulmonary Hypertension

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ClinicalTrials.gov Identifier: NCT00850369
Recruitment Status : Withdrawn (Slow accrual onto the study)
First Posted : February 25, 2009
Last Update Posted : July 29, 2013
Sponsor:
Collaborator:
Duke University
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

Tracking Information
First Submitted Date  ICMJE February 22, 2009
First Posted Date  ICMJE February 25, 2009
Last Update Posted Date July 29, 2013
Study Start Date  ICMJE February 2005
Actual Primary Completion Date May 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 24, 2009)
  • Pulmonary artery systolic pressure (mm Hg) [ Time Frame: 2 years ]
  • Pulmonary vascular resistance (dyne.s.cm-5) [ Time Frame: 2 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT00850369 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 24, 2009)
  • Six-minute walk [ Time Frame: 2 years ]
  • Markers of thrombin generation (TAT complexes, F1.2, d-dimers) [ Time Frame: 2 years ]
  • Markers of platelet activation (soluble CD40 ligand, beta thromboglobulin, platelet factor [ Time Frame: 2 years ]
  • Nitric oxide metabolites [ Time Frame: 2 years ]
  • Quality of life [ Time Frame: 2 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Pilot Study of Chronic Red Blood Cell Transfusion in Sickle Cell Disease-Associated Pulmonary Hypertension
Official Title  ICMJE A Pilot Study of the Effects of Chronic Red Blood Cell Transfusion in Sickle Cell Disease On Pulmonary Hypertension in Patients With Sickle Cell Disease
Brief Summary

Pulmonary hypertension, a complication associated with an increased risk of death, is common in patients with sickle cell disease. Despite its frequency, there remains no standard treatment for this complication in patients with sickle cell disease.

In this small study, the investigators will evaluate the effect of monthly transfusion of red blood cells to patients with sickle cell disease-associated pulmonary hypertension. The investigators speculate that by increasing the hemoglobin level and decreasing the amount of sickle red blood cells, these patients would experience improvements in their PHT.

Detailed Description

As patients with sickle cell disease (SCD) age, recurrent vaso-occlusive episodes lead to progressive end-organ damage. Pulmonary hypertension (PHT) represents an example of such end-organ damage. Pulmonary hypertension, a common complication in patients with sickle cell disease (SCD), results in a shortened survival. The high mortality reported in SCD patients with PHT appears to occur particularly in those patients with moderate and severe elevations in their pulmonary artery pressure. The overall objective of this proposal is to evaluate the effect of chronic red blood cell transfusion on PHT in SCD. We hypothesize that by increasing the hemoglobin concentration and decreasing the amount of HbS, these patients would experience improvements in their PHT.

Thus, the specific aim of this clinical trial is to evaluate the effects of RBC transfusion on pulmonary hypertension in SCD, as well as the effect of chronic RBC transfusion on plasma markers of thrombin generation, platelet activation, and nitric oxide metabolites.

Study subjects will be transfused monthly for 6 months to investigate the safety and efficacy of RBC transfusion in SCD patients with PHT. All packed red blood cells will have extended antigen matching for C, D, E and Kell to minimize the risk of alloimmunization. Subjects will receive other routine treatments for SCD. Specific outcome variables will be evaluated at 1 month, 3 months, and 6 months. All study subjects will receive simple transfusion of packed red blood cell to achieve a post-transfusion hemoglobin (Hb) not greater than 10 g/dL. For those subjects who may have baseline hemoglobins in whom a post transfusion Hb would exceed 10 g/dL, they will require a limited exchange transfusion, i.e. phlebotomy of 1 unit of blood, followed by transfusion of 2 units of packed RBC. All study subjects will return for assessment of safety and/or efficacy measures every two weeks for the first month, and subsequently every four weeks till the completion of the study. Study subjects who experience a documented worsening of their disease (decreased SaO2, worsening 6-minute walk) on at least two consecutive follow up visits will be taken off the study. At the end of the study, subjects will have the option of continuing on chronic RBC transfusion.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Pulmonary Hypertension
  • Sickle Cell Disease
Intervention  ICMJE Other: RBC transfusion
Study subjects will receive monthly transfusions with 2 units of red blood cells
Study Arms  ICMJE Experimental: 1
All subjects wil receive monthly RBC transfusions for 6 months
Intervention: Other: RBC transfusion
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: November 4, 2011)
0
Original Estimated Enrollment  ICMJE
 (submitted: February 24, 2009)
20
Actual Study Completion Date  ICMJE May 2011
Actual Primary Completion Date May 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. diagnosis of sickle cell anemia (HbSS) and HbSbeta0 thalassemia;
  2. male and female subjects between 18 and 65 years;
  3. documented PHT, but with pulmonary artery systolic pressures >/= 45 mmHg (TR jet velocity of >/= 3.0 m/s) on at least 2 separate visits at least 1 month apart;
  4. ability to give written informed consent to participate in the study; and
  5. in non-crisis steady state at time of enrollment

Exclusion Criteria:

  1. treatment with epoprostenol (flolan) or similar prostacyclin analog, bosentan or sildenafil (or similar phosphodiesterase 5 inhibitor)
  2. on chronic anticoagulation
  3. RBC transfusion in previous 90 days;
  4. use of hydroxyurea
  5. multiple red cell alloantibodies that will make transfusion unsafe;
  6. baseline ferritin level > 1000 mg/dL
  7. pregnancy, and/or any condition which in the opinion of investigator might make the subject unsuitable for the study;
  8. patients with WHO functional class IV
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries United States
 
Administrative Information
NCT Number  ICMJE NCT00850369
Other Study ID Numbers  ICMJE R01-HL79915-1
HL799151
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of North Carolina, Chapel Hill
Study Sponsor  ICMJE University of North Carolina, Chapel Hill
Collaborators  ICMJE Duke University
Investigators  ICMJE
Principal Investigator: Kenneth I Ataga, MD University of North Carolina, Chapel Hill
PRS Account University of North Carolina, Chapel Hill
Verification Date July 2013

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