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

Sickle Cell Disease Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00850369
• Other study ID #: R01-HL79915-1
• Secondary ID: HL799151
• Status: Withdrawn
• Phase: Phase 2
• First received: February 22, 2009
• Last updated: July 26, 2013
• Start date: February 2005
• Est. completion date: May 2011

Study information

• Verified date: July 2013
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: May 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Hypertension
• Hypertension, Pulmonary
• Pulmonary Hypertension
• Sickle Cell Disease

Intervention

Other:
• RBC transfusion
Study subjects will receive monthly transfusions with 2 units of red blood cells

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	Duke University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pulmonary artery systolic pressure (mm Hg)		2 years	No
Primary	Pulmonary vascular resistance (dyne.s.cm-5)		2 years	No
Secondary	Six-minute walk		2 years	No
Secondary	Markers of thrombin generation (TAT complexes, F1.2, d-dimers)		2 years	No
Secondary	Markers of platelet activation (soluble CD40 ligand, beta thromboglobulin, platelet factor		2 years	No
Secondary	Nitric oxide metabolites		2 years	No
Secondary	Quality of life		2 years	No