鎌状赤血球症と CardiovAscular リスク - 赤血球交換試験 (SCD-CARRE) (SCD-CARRE)
The SCD-CARRE trial is a Phase 3, prospective, randomized, multicenter, controlled, parallel two-arm study aimed to determine if automated exchange blood transfusion and standard of care administered to high mortality risk adult SCD patients reduces the total number of episodes of clinical worsening of SCD requiring acute health care encounters (non-elective infusion center/ER/hospital visits) or resulting in death over 12 months as compared with standard of care.
調査の概要
詳細な説明
As patients with sickle cell disease (SCD) live to adulthood, the chronic impact of sustained hemolytic anemia and episodic vaso-occlusive events take their toll, with the progressive development of cardiopulmonary organ dysfunction. This culminates in the development of pulmonary hypertension, left ventricular diastolic heart disease, dysrhythmia, chronic kidney disease and sudden death, all major cardiovascular complications of SCD for which there are no approved or consensus therapies. The risk of having pulmonary hypertension and diastolic heart disease can be non-invasively assessed by laboratory tests (NT-proBNP) and Doppler-echocardiography (estimated pulmonary artery systolic pressure). A recent meta-analysis of approximately 6000 patients with SCD demonstrated that patients with elevated tricuspid regurgitant jet velocity (TRV), which is an Doppler-echocardiographic measurement that estimates the pulmonary artery systolic pressure, walked an estimated 30.4 meters less in a 6 minute walk test than those without elevated TRV, and elevated TRV was associated with high mortality (hazard ratio of 4.9). In two large registry cohorts of adult patients with SCD, the investigators found that approximately 20% of the adult SCD population have high values for both biomarkers, defined as a TRV ≥ 2.5 meters per second AND a NT-proBNP ≥ 160 pg/mL, and that the 12-month mortality rate is 7.9% in this group as compared to 0.5% in patients with normal TRV or NT-proBNP values, with a risk ratio for hospitalization of 1.6. This suggests that a simple screening profile of TRV and NT-proBNP can identify about 20% of patients with SCD at the highest risk of death and hospitalization.
Given the increased mortality and early loss of functional capacity associated with cardiovascular disease in SCD adults, it is important to test effective therapeutic interventions in such patients. Red blood cell transfusions are administered by either simple or exchange transfusion, the latter removes the patients blood and replaces it with transfused red blood cells. Exchange transfusions have proven effective for acute treatment of almost all SCD complications, including severe acute chest syndrome, stroke, splenic or hepatic sequestration, and multi-organ failure, and are also used chronically for stroke prevention and recurrent acute chest syndrome. In this study the investigators hypothesize that monthly exchange transfusion will limit disease progression, improve exercise capacity, and prevent interval episodes of vaso-occlusive painful crisis and the acute chest syndrome that acutely increases pulmonary pressures and cause right heart failure.
The investigators propose to perform a clinical trial to evaluate the effects of automated exchange blood transfusion on patient morbidity and mortality, compared to standard of care among 150 adult high risk SCD patients. The trial will leverage existing coordinating center infrastructure at the University of Pittsburgh and will involve 22 experienced clinical sites. Despite the safety and wide utilization of erythrocytapheresis in adult patients with SCD, there is no consensus or quality efficacy data on its use to improve outcomes in our aging high-risk SCD patients with progressive end-organ dysfunction.
研究の種類
入学 (実際)
段階
- フェーズ 3
連絡先と場所
研究場所
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Alabama
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Tuscaloosa、Alabama、アメリカ、35401
- University of Alabama
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California
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Oakland、California、アメリカ、94609
- UCSF Benioff Children's Hospital Oakland
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District of Columbia
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Washington D.C.、District of Columbia、アメリカ、20060
- Howard University Center for Sickle Cell Disease
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Georgia
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Atlanta、Georgia、アメリカ、30322
- Emory University
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Illinois
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Chicago、Illinois、アメリカ、60607
- University of Illinois at Chicago
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Maryland
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Baltimore、Maryland、アメリカ、21201
- University of Maryland
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Baltimore、Maryland、アメリカ、21206
- Johns Hopkins University
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Massachusetts
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Boston、Massachusetts、アメリカ、02118
- Boston Medical Center
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Missouri
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St Louis、Missouri、アメリカ、63110
- Washington University-St. Louis
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New York
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New York、New York、アメリカ、10029
- Icahn School of Medicine at Mount Sinai
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New York、New York、アメリカ、10461
- Montefiore Medical Center
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North Carolina
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Chapel Hill、North Carolina、アメリカ、27599
- University of North Carolina at Chapel Hill
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Charlotte、North Carolina、アメリカ、28204
- Atrium Health
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Durham、North Carolina、アメリカ、27708
- Duke University
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Greenville、North Carolina、アメリカ、27834
- East Carolina University
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Ohio
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Cleveland、Ohio、アメリカ、44106
- University Hospitals Cleveland Medical Center
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Columbus、Ohio、アメリカ、43210
- Ohio State University
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Pennsylvania
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Pittsburgh、Pennsylvania、アメリカ、15232
- University of Pittsburgh Medical Center
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Texas
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Houston、Texas、アメリカ、77030
- University of Texas Health Science Center at Houston
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Virginia
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Richmond、Virginia、アメリカ、23284
- Virginia Commonwealth University
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Créteil、フランス
- Kremlin-Bicêtre
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Paris、フランス
- Henri Mondor Hopital
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Rio de Janeiro、ブラジル
- Hemorio
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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:
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Age 18 years or older
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Diagnosis of SCD: homozygous sickle cell disease, hemoglobin-SC, Sβ-thalassemia, hemoglobin-SO or hemoglobin-SD.
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Patients not on a chronic exchange transfusion program for at least 60 days.
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If patients are on a SCD drug (e.g. hydroxyurea, glutamine, or P-selectin inhibitors), the doses must be stable for at least 60 days prior to randomization. At the time of randomization, participants must be off Oxbryta for at least 30 days.
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Any one of the following vasculopathy biomarker clinical results (a, b, c, d or e) measured in the last 24 months before randomization that indicates a high-risk patient:
- Both a TRV 2.5- <3.0 m/sec and NT-proBNP plasma level ≥ 160 pg/mL,
- TRV ≥ 3.0 m/sec,
- Both a mean pulmonary artery pressure (PAP) by right heart catheterization 20-24 mmHg and NT-proBNP plasma level ≥ 160 pg/mL,
- Mean PAP by right heart catheterization ≥ 25 mmHg,
- Chronic kidney disease (CKD) due to SCD with abnormal measures on 2 separate occasions as defined by: macroalbuminuria (albumin to creatinine ratio (ACR) >300 mg/g) or proteinuria (protein to creatinine ratio >30 mg/mmol), or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. (It is recommended that local laboratories use Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation without ethnic factors when estimating and reporting GFR).
Clinical results of these biomarkers measured locally at sites within 24 months prior to randomization are acceptable to determine eligibility. TRV, PAP, NT-proBNP, albumin to creatinine ratio, protein to creatinine ratio, or eGFR values must be measured in a steady state (defined as measured ≥ 14 days since an acute care pain event) on different days.
vi. Written informed consent obtained from patient to participate in the trial.
Exclusion Criteria:
- RBC alloimmunization resulting in inability of blood bank to obtain compatible components for chronic exchange transfusions
- Previous history of hyper-hemolysis syndrome
- Previous history of severe transfusion reaction resulting in renal failure or due to serious complications such as hypotension or respiratory distress
- More than 10 vaso-occlusive episodes in the past 12 months requiring admission to a hospital to receive treatment.
- Religious objection to receiving blood transfusion
- Diagnosis of ischemic stroke within the past 6 months
- Clinical evidence of liver failure or advanced cirrhosis or any co-existing medical condition that in the Investigator's judgement will substantially increase the risk associated with the patient's participation in the trial
- Women of childbearing potential who have a positive pregnancy test at baseline
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：ランダム化
- 介入モデル：並列代入
- マスキング：独身
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：Exchange transfusion plus standard of care
Randomized to standard of care and automated exchange blood transfusion every 3-6 weeks for 12 months. |
Red blood cell exchange transfusions will be performed every 3-6 weeks to maintain a target post-transfusion hemoglobin S level of <20% and a pre-transfusion hemoglobin S of <30%.
他の名前：
NHLBI/ASH/ATS Expert Panel recommended guidelines |
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アクティブコンパレータ：Standard of care
Randomized to standard of care |
NHLBI/ASH/ATS Expert Panel recommended guidelines |
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 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Episodes of clinical worsening
時間枠：13 months
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The efficacy of the intervention will be measured by comparing the total number of episodes of clinical worsening of SCD requiring acute health care encounters (non-elective infusion center/ER/Hospital visits) or resulting in death over 13 months between groups. |
13 months
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Acute healthcare event
時間枠：13 months
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A 6-level prioritized rank-based outcome: 1.No death or SCD-related acute health care encounters (SCDAcuteE) within (w/in) 13 months (m) of randomization; 2. Had SCDAcuteE but NO major complications (acute kidney injury (AKI), acute chest syndrome (ACS), cor pulmonale, stroke, liver failure) associated with an SCDAcuteE nor death w/in 13 m of randomization; 3. Had 1 major complication (AKI, ACS, cor pulmonale, stroke, or liver failure) associated with an SCDAcuteE but not death w/in 13 m of randomization; 4. Had 2 major complications (AKI, ACS, cor pulmonale, stroke, or liver failure) associated with SCDAcuteE but not death w/in 13 m of randomization; 5. Had ≥ 3 major complications (AKI, ACS, cor pulmonale, stroke, or liver failure) associated with SCDAcuteE but not death w/in 13 m of randomization; 6.Death w/in 13 m of randomization. If the same complication reoccurs, occurrences will be counted as separate complications if the acute health care encounters are separated by ≥7 days. |
13 months
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Twelve-month survival
時間枠：13 months
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Survival over thirteen-month period will be analyzed and compared between the group receiving the intervention and the group receiving care routinely provided for sickle cell patients based on the NHLBI guidelines. |
13 months
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Survival free of acute healthcare encounters
時間枠：13 months
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Survival free of acute health care encounters over 13 months. |
13 months
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Total number of acute health care encounters
時間枠：13 months
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The total number of acute health care encounters (non-elective infusion center/ER/Hospital visits) with evidence of cor pulmonale (physical exam findings, NT-proBNP increase plus echocardiographic evidence of worsening right heart function). |
13 months
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Measures of exercise capacity - 6 minute walk distance
時間枠：4, 8, and 12 months
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Measures of exercise capacity assessed at 4, 8 and 12 months by the distance walked in the six minute walk distance assessment |
4, 8, and 12 months
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Measures of exercise capacity - outpatient activity
時間枠：4, 8, and 12 months
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Measures of exercise capacity assessed at 4, 8 and 12 months by the distance walked in a 7 day in the outpatient setting. |
4, 8, and 12 months
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Cardiovascular risk
時間枠：12 months
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Established cardiovascular risk biomarkers and indices are combined to help the investigators form an opinion about cardiovascular risks. The following will be measured: NT-proBNP, QT prolongation, systemic pulse pressure, albuminuria, estimated GFR and CKD progression Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group criteria. |
12 months
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Development of new leg ulcers
時間枠：4, 8 and 12 months
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Participants will be assessed for development of new leg ulcers at each physical exam. |
4, 8 and 12 months
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Measures of exercise capacity - WHO Classification
時間枠：4, 8 and 12 months
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WHO functional status severity will be measured assessing by looking at limitation of usual physical activity from I (no limitation in usual physical activity) to Class IV (inability to perform any physical activity at rest) |
4, 8 and 12 months
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Nocturnal desaturation
時間枠：4, 8 and 12 months
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Nocturnal desaturation will measured using a wearable device to measure blood oxygen saturation for 7 nights at home. |
4, 8 and 12 months
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SCD specific patient reported outcomes - Pain
時間枠：4, 8 and 12 months
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SCD specific patient reported outcomes as measured by self-reported pain |
4, 8 and 12 months
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SCD specific patient reported outcomes -Quality of Life modified PROMIS scale
時間枠：4, 8 and 12 months
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SCD specific patient reported outcomes as measured by a modified version of health related quality of life questionnaire from PROMIS QoL measure |
4, 8 and 12 months
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SCD specific patient reported outcomes -Quality of Life modified ASCQ-Me scale
時間枠：4, 8 and 12 months
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SCD specific patient reported outcomes as measured by a modified version of health related quality of life questionnaire from ASCQ-Me QoL measure |
4, 8 and 12 months
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Cardiovascular function by echocardiography - TRV
時間枠：4, 8 and 12 months
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Cardiovascular function measures from echocardiography assessed at 4, 8 and 12 months: echocardiographic measures of tricuspid regurgitant jet velocity in m/s. |
4, 8 and 12 months
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Cardiovascular function by echocardiography - diastolic left heart function
時間枠：4, 8 and 12 months
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Diastolic left heart function measured by E/A ratio, E/Em ratio, and deceleration times will be assessed by echocardiography. |
4, 8 and 12 months
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Cardiovascular function by echocardiography - systolic right heart function
時間枠：4, 8 and 12 months
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Systolic right heart health will be measured by assessing tricuspid annular plane systolic excursion (TAPSE), right ventricular size and contractility from echocardiography of the heart. |
4, 8 and 12 months
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Total number of acute health care encounters
時間枠：13 months
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The number of acute health care encounters (non-elective infusion center/ER/Hospital visits) with at least one major complication. |
13 months
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協力者と研究者
スポンサー
捜査官
- 主任研究者：Maria Brooks, PhD、University of Pittsburgh
- スタディチェア：Mark Gladwin, MD、University of Maryland
- 主任研究者：Darrell Triulzi, MD、University of Pittsburgh
出版物と役立つリンク
一般刊行物
- Abbasi M, Srivastava A, Saraf SL. Management of Kidney Disease with Sickle Cell Disease. J Am Soc Nephrol. 2025 Oct 1;36(10):2041-2054. doi: 10.1681/ASN.0000000804. Epub 2025 Jun 26.
- Bertolet M, Triulzi DJ, Campbell-Lee S, Gordeuk VR, Herbert BM, Novelli E, Jonassaint C, Villanueva F, Chien N, Gladwin MT, Brooks MM; SCD-CARRE Investigators. Design, rationale, and baseline patient characteristics for the Sickle Cell Disease and CardiovAscular Risk-Red cell Exchange (SCD-CARRE) trial. Am Heart J. 2026 Jul 15;301:107542. doi: 10.1016/j.ahj.2026.107542. Online ahead of print.
研究記録日
主要日程の研究
研究開始 (実際)
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 (実際)
学習記録の更新
投稿された最後の更新 (実際)
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
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- STUDY20110362
- UG3HL143192 (米国 NIH グラント/契約)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
Results from research conducted under this project will be shared in several ways. Manuscripts will be submitted for publication in high-quality peer-reviewed journals, following the NIH Public Access Policy guidelines. Findings will be presented at relevant national conferences, public lectures, scientific institutions and meetings. The timeline for participant recruitment, data collection and analysis will foster publication, facilitated by the investigators' Publications Committee, of critically important and clinically relevant data throughout the trial. The study datasets will be archived and made available to qualified individuals after a period of exclusive use by the SCD-CARRE trial research team and after publication of the primary manuscripts, following NIH guidelines.
IPD 共有時間枠
At the end of the trial, study de-identified datasets will be submitted for permanent archive in the NHLBI BioLINCC repository. The trial will also produce deliverables that will be freely available to the sickle cell community including a description of the protocol for automated red blood cell exchange transfusion.
IPD 共有アクセス基準
All publications based on the SCD-CARRE trial will adhere to the NIH Public Access Policy (Notice NOT-OD-08-033). All study data will be de-identified. At the end of the trial, study de-identified datasets will be submitted for permanent archive in the NHLBI BioLINCC repository.
The investigators also will work closely with regional and National SCD Foundations to promote recruitment for this study and communicate our results.
IPD 共有サポート情報タイプ
- CSR
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
米国で製造され、米国から輸出された製品。
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。