Remote Ischemic Preconditioning After Cardiac Surgery (RIPCRenal)
Remote Ischemic Preconditioning to Prevent Acute Kidney Injury in High Risk Patients After Cardiac Surgery (RIPCRenal)
調査の概要
詳細な説明
Acute kidney injury (AKI) complicates 7-19% of cardiac surgical procedures. The investigators recently found that remote ischemic preconditioning (RIPC) using transient external compression of the upper arm prior to cardiac surgery was effective for reducing the occurrence of AKI (37.5% compared to 52.5% with sham; absolute risk reduction (ARR),15%; 95% CI, 2.56% to 27.44%; P=0.02). Fewer patients treated with RIPC received renal replacement therapy (RRT) (5.8% versus 15.8%; ARR, 10%; 95% CI, 2.25% to 17.75%; P=0.01). Moreover, the investigators found that the effectiveness of this intervention was strongly associated with the release of cell-cycle arrest biomarkers into the urine. Patients with urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 ([TIMP-2]•[IGFBP7]) ≥ 0.5 (ng/ml)(ng/ml)/1000 before surgery had a significantly reduced rate of AKI compared to patients with lower urinary [TIMP-2]•[IGFBP7] concentration (relative risk (RR), 67%; 95% CI, 53% to 83%, P<0.001) whereas the biomarker concentrations after surgery predicted AKI as previously shown. This effect makes sense because cell-cycle arrest is thought to be part of the protective mechanisms endothelial cells use when exposed to stress. Stimulating these responses with RIPC should reduce AKI. Importantly, only 56% of patients treated with RIPC achieved an increase in urine [TIMP-2]•[IGFBP7] to ≥ 0.5, and only in this group was the intervention effective-patients that did not achieve this level showed no benefit.
Our goal is to eventually design and conduct a Bayesian 2-stage adaptive design sequence trial to evaluate the effectiveness of RIPC to prevent AKI in patients undergoing cardiac surgery. The dimensions of dose include duration, intensity and number of cycles. However, before this trial can be designed we need to answer 4 questions: i. Do baseline urinary [TIMP-2]•[IGFBP7] levels predict AKI (enrichment)? ii. Do [TIMP-2]•[IGFBP7] changes elicited by RIPC predict protection (RIPC efficacy measure)? iii. Is there a dose-response relationship between RIPC "dose" and [TIMP-2]•[IGFBP7]? iv. Is a dose-escalation RIPC protocol where doses are increased for non-responders, feasible and safe within the anesthesia workflow for cardiac surgery cases (practical)?
研究の種類
入学 (予想される)
段階
- 適用できない
連絡先と場所
研究場所
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Muenster、ドイツ、D-48149
- 募集
- University Hospital Muenster
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コンタクト：
- Alexander Zarbock, PhD, MD
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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:
- Patients who are scheduled to undergo cardiac surgery with cardiopulmonary bypass
- Cleveland Clinic Score >=6
Exclusion Criteria:
- Acute myocardial infarction up to 7 days before surgery
- Age < 18 years
- Off-pump cardiac surgery
- Preexisting AKI
- Chronic kidney disease (GFR < 30 ml/min)
- Kidney transplantation within the last 12 months
- Peripheral arterial occlusive disease
- Pregnancy
- Hepatorenal syndrome
- Sulfonamide or thiazide medication within the last 7 days
- Participation in another interventional trial
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：トリプル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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介入なし：Observational group
No intervention, standard care
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偽コンパレータ：Sham RIPC
Three cycles of 5- min upper limb sham ischemia
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3 cycles or more cycles of 5 to 10-min inflation of a blood-pressure cuff to 200 mm HG (or at least to a pressure 50 mmHG higher than the systolic arterial pressure) to one upper arm followed by 5 min reperfusion with the cuff deflated.
In Non-Responder two additional cycles of 10 min cuff inflation will be performed in arm 6.
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実験的：RIPC-Group 1
Three cycles of 5- min upper limb ischemia
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3 cycles or more cycles of 5 to 10-min inflation of a blood-pressure cuff to 200 mm HG (or at least to a pressure 50 mmHG higher than the systolic arterial pressure) to one upper arm followed by 5 min reperfusion with the cuff deflated.
In Non-Responder two additional cycles of 10 min cuff inflation will be performed in arm 6.
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実験的：RIPC-Group 2
Three cycles of 7-min upper limb ischemia
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3 cycles or more cycles of 5 to 10-min inflation of a blood-pressure cuff to 200 mm HG (or at least to a pressure 50 mmHG higher than the systolic arterial pressure) to one upper arm followed by 5 min reperfusion with the cuff deflated.
In Non-Responder two additional cycles of 10 min cuff inflation will be performed in arm 6.
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実験的：RIPC-Group 3
Three cycles of 10-min upper limb ischemia
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3 cycles or more cycles of 5 to 10-min inflation of a blood-pressure cuff to 200 mm HG (or at least to a pressure 50 mmHG higher than the systolic arterial pressure) to one upper arm followed by 5 min reperfusion with the cuff deflated.
In Non-Responder two additional cycles of 10 min cuff inflation will be performed in arm 6.
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実験的：RIPC-Group 4
Three Cycles of 5-min upper limb ischemia.
If there is no response this will be followed by 2 cycles of 10-min upper-limb ischemia
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3 cycles or more cycles of 5 to 10-min inflation of a blood-pressure cuff to 200 mm HG (or at least to a pressure 50 mmHG higher than the systolic arterial pressure) to one upper arm followed by 5 min reperfusion with the cuff deflated.
In Non-Responder two additional cycles of 10 min cuff inflation will be performed in arm 6.
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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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Change in urinary [TIMP-2]*[IGFBP7]
時間枠：within 12 hours after CPB
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Biomarkers will be measured at different time points after to evaluate the effect of RIPC on [TIMP-2]*[IGFBP7]
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within 12 hours after CPB
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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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AKI within 72 hours
時間枠：72 h
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72 h
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Dialysis within 7 days of surgery
時間枠：7 days
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7 days
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All-cause-mortality at 90 days
時間枠：90 d
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90 d
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Dialysis at day 90
時間枠：90 days
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90 days
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Renal recovery at day 90
時間枠：90 days
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90 days
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MAKE 90
時間枠：90 days
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major adverse kidney events
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90 days
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協力者と研究者
捜査官
- スタディチェア：Melanie Meersch、University Hospital Muenster
研究記録日
主要日程の研究
研究開始
一次修了 (予想される)
研究の完了 (予想される)
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 (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
その他の研究ID番号
- 04-AnIt-16
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?
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