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

This study has been terminated.
(Slow accrual onto the study)
Sponsor:
Collaborator:
Duke University
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT00850369
First received: February 22, 2009
Last updated: November 4, 2011
Last verified: November 2011
History of Changes
  Purpose

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.


Condition Intervention Phase
Pulmonary Hypertension
Sickle Cell Disease
 Other: RBC transfusion
 Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Pulmonary artery systolic pressure (mm Hg) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Pulmonary vascular resistance (dyne.s.cm-5) [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Six-minute walk [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Markers of thrombin generation (TAT complexes, F1.2, d-dimers) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Markers of platelet activation (soluble CD40 ligand, beta thromboglobulin, platelet factor [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Nitric oxide metabolites [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Quality of life [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: February 2005
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
All subjects wil receive monthly RBC transfusions for 6 months
 Other: RBC transfusion
Study subjects will receive monthly transfusions with 2 units of red blood cells

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00850369

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Duke University
Investigators
Principal Investigator: Kenneth I Ataga, MD University of North Carolina, Chapel Hill
  More Information

No publications provided

Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT00850369     History of Changes
Other Study ID Numbers: R01-HL79915-1, HL799151
Study First Received: February 22, 2009
Last Updated: November 4, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by University of North Carolina, Chapel Hill:
Pulmonary hypertension
Sickle cell disease

Additional relevant MeSH terms:
Anemia, Sickle Cell
Hypertension
Hypertension, Pulmonary
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
 Hemoglobinopathies
Genetic Diseases, Inborn
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on May 22, 2013