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

NCT ID: NCT00850369

Last Updated: 2013-07-29

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-02-28
• Study Completion Date: 2011-05-31

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.

Conditions

Pulmonary Hypertension; Sickle Cell Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

All subjects wil receive monthly RBC transfusions for 6 months

Group Type: EXPERIMENTAL

RBC transfusion

Intervention Type: OTHER

Study subjects will receive monthly transfusions with 2 units of red blood cells

Interventions

RBC transfusion

Study subjects will receive monthly transfusions with 2 units of red blood cells

Intervention Type: OTHER

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Duke University

OTHER

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kenneth I Ataga, MD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Other Identifiers

HL799151

Identifier Type: -

Identifier Source: secondary_id

R01HL079915

Identifier Type: NIH

Identifier Source: secondary_id

View Link

R01-HL79915-1

Identifier Type: -

Identifier Source: org_study_id