A Pilot Study of Chronic Red Blood Cell Transfusion in Sickle Cell Disease-Associated Pulmonary Hypertension
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.
調査の概要
詳細な説明
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.
研究の種類
段階
- フェーズ2
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:なし
- 介入モデル:単一グループの割り当て
- マスキング:なし(オープンラベル)
武器と介入
参加者グループ / アーム |
介入・治療 |
---|---|
実験的:1
All subjects wil receive monthly RBC transfusions for 6 months
|
Study subjects will receive monthly transfusions with 2 units of red blood cells
|
この研究は何を測定していますか?
主要な結果の測定
結果測定 |
時間枠 |
---|---|
Pulmonary artery systolic pressure (mm Hg)
時間枠:2 years
|
2 years
|
Pulmonary vascular resistance (dyne.s.cm-5)
時間枠:2 years
|
2 years
|
二次結果の測定
結果測定 |
時間枠 |
---|---|
生活の質
時間枠:2年
|
2年
|
Six-minute walk
時間枠:2 years
|
2 years
|
Markers of thrombin generation (TAT complexes, F1.2, d-dimers)
時間枠:2 years
|
2 years
|
Markers of platelet activation (soluble CD40 ligand, beta thromboglobulin, platelet factor
時間枠:2 years
|
2 years
|
Nitric oxide metabolites
時間枠:2 years
|
2 years
|
協力者と研究者
協力者
捜査官
- 主任研究者:Kenneth I Ataga, MD、University of North Carolina, Chapel Hill
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
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