Pulmonary HypertensionPhase 2NCT00850369
A Pilot Study of Chronic Red Blood Cell Transfusion in Sickle Cell Disease-Associated Pulmonary Hypertension
A Phase 2 study testing RBC transfusion in people with Pulmonary Hypertension and Sickle Cell Disease, run by University of North Carolina, Chapel Hill.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Pulmonary Hypertension, Sickle Cell Disease
- What is being tested?
- RBC transfusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Feb 2005to May 2011
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- diagnosis of sickle cell anemia (HbSS) and HbSbeta0 thalassemia;
- male and female subjects between 18 and 65 years;
- 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;
- ability to give written informed consent to participate in the study; and
- in non-crisis steady state at time of enrollment
Who cannot join
- treatment with epoprostenol (flolan) or similar prostacyclin analog, bosentan or sildenafil (or similar phosphodiesterase 5 inhibitor)
- on chronic anticoagulation
- RBC transfusion in previous 90 days;
- use of hydroxyurea
- multiple red cell alloantibodies that will make transfusion unsafe;
- baseline ferritin level > 1000 mg/dL
- pregnancy, and/or any condition which in the opinion of investigator might make the subject unsuitable for the study;
- patients with WHO functional class IV
About this study
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
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.
Read the 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
- Being tested
- RBC transfusion
- Keywords
- Pulmonary hypertension, Sickle cell disease
- Medical subject headings
- Hypertension, Pulmonary, Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RBC transfusionOther
Study subjects will receive monthly transfusions with 2 units of red blood cells
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | All subjects wil receive monthly RBC transfusions for 6 months Receives: Other: RBC transfusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pulmonary artery systolic pressure (mm Hg)
Measured: 2 years
Pulmonary vascular resistance (dyne.s.cm-5)
Measured: 2 years
Secondary outcomes (5)
Six-minute walk
Measured: 2 years
Markers of thrombin generation (TAT complexes, F1.2, d-dimers)
Measured: 2 years
Markers of platelet activation (soluble CD40 ligand, beta thromboglobulin, platelet factor
Measured: 2 years
Nitric oxide metabolites
Measured: 2 years
Quality of life
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2009 (estimated)
- Study startFeb 2005
- Primary completionMay 2011
- Study completionMay 2011
Why it stopped: Slow accrual onto the study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary HypertensionStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- Duke University
- Responsible party
- Sponsor
- Investigators
- Kenneth I Ataga, MD, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00850369
- Sponsor's protocol ID
- R01-HL79915-1
- Other IDs
- HL799151, R01HL079915
- Status last verified
- Jul 2013
- First submitted
- 22 Feb 2009
- Last updated
- 29 Jul 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00850369
- Acronym / sponsor ID
- R01-HL79915-1
- Conditions
- Pulmonary Hypertension, Sickle Cell Disease
- Keywords
- Pulmonary hypertension, Sickle cell disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Slow accrual onto the study
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- Duke University
- Study start
- Feb 2005
- Primary completion
- May 2011 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 25 Feb 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Other: RBC transfusionAll subjects wil receive monthly RBC transfusions for 6 months |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- diagnosis of sickle cell anemia (HbSS) and HbSbeta0 thalassemia;
- male and female subjects between 18 and 65 years;
- 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;
- ability to give written informed consent to participate in the study; and
- in non-crisis steady state at time of enrollment
Key exclusion criteria (8 listed)
- treatment with epoprostenol (flolan) or similar prostacyclin analog, bosentan or sildenafil (or similar phosphodiesterase 5 inhibitor)
- on chronic anticoagulation
- RBC transfusion in previous 90 days;
- use of hydroxyurea
- multiple red cell alloantibodies that will make transfusion unsafe;
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 |
|---|---|---|
| RBC transfusionStudy subjects will receive monthly transfusions with 2 units of red blood cells | Other | 1 |
Primary outcome
Pulmonary artery systolic pressure (mm Hg)
Time frame: 2 years
Pulmonary vascular resistance (dyne.s.cm-5)
Time frame: 2 years
5 secondary outcomes
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
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2013.
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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.
Kenneth I Ataga, MD principal investigator
University of North Carolina, Chapel Hill
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing RBC transfusion in people with Pulmonary Hypertension and Sickle Cell Disease, run by University of North Carolina, Chapel Hill.
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 5 inclusion and 8 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: withdrawn, as of the sponsor's last update on 29 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.
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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Pulmonary artery systolic pressure (mm Hg) (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Jul 2013.