Remote Ischemic Preconditioning After Cardiac Surgery (RIPCRenal)
Remote Ischemic Preconditioning to Prevent Acute Kidney Injury in High Risk Patients After Cardiac Surgery (RIPCRenal)
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
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)?
Tipo di studio
Iscrizione (Anticipato)
Fase
- Non applicabile
Contatti e Sedi
Luoghi di studio
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Muenster, Germania, D-48149
- Reclutamento
- University hospital Muenster
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Contatto:
- Alexander Zarbock, PhD, MD
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Triplicare
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
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Nessun intervento: Observational group
No intervention, standard care
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Comparatore fittizio: 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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Sperimentale: 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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Sperimentale: 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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Sperimentale: 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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Sperimentale: 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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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Change in urinary [TIMP-2]*[IGFBP7]
Lasso di tempo: 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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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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AKI within 72 hours
Lasso di tempo: 72 h
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72 h
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Dialysis within 7 days of surgery
Lasso di tempo: 7 days
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7 days
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All-cause-mortality at 90 days
Lasso di tempo: 90 d
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90 d
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Dialysis at day 90
Lasso di tempo: 90 days
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90 days
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Renal recovery at day 90
Lasso di tempo: 90 days
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90 days
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MAKE 90
Lasso di tempo: 90 days
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major adverse kidney events
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90 days
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Collaboratori e investigatori
Sponsor
Collaboratori
Investigatori
- Cattedra di studio: Melanie Meersch, University hospital Muenster
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Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
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Ultimo aggiornamento inviato che soddisfa i criteri QC
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Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- 04-AnIt-16
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