Remote Ischemic Preconditioning After Cardiac Surgery (RIPCRenal)
Remote Ischemic Preconditioning to Prevent Acute Kidney Injury in High Risk Patients After Cardiac Surgery (RIPCRenal)
Přehled studie
Postavení
Intervence / Léčba
Detailní popis
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)?
Typ studie
Zápis (Očekávaný)
Fáze
- Nelze použít
Kontakty a umístění
Studijní místa
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Muenster, Německo, D-48149
- Nábor
- University hospital Muenster
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Kontakt:
- Alexander Zarbock, PhD, MD
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
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
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Trojnásobný
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Žádný zásah: Observational group
No intervention, standard care
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Falešný srovnávač: 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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Experimentální: 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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Experimentální: 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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Experimentální: 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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Experimentální: 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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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Change in urinary [TIMP-2]*[IGFBP7]
Časové okno: 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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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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AKI within 72 hours
Časové okno: 72 h
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72 h
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Dialysis within 7 days of surgery
Časové okno: 7 days
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7 days
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All-cause-mortality at 90 days
Časové okno: 90 d
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90 d
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Dialysis at day 90
Časové okno: 90 days
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90 days
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Renal recovery at day 90
Časové okno: 90 days
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90 days
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MAKE 90
Časové okno: 90 days
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major adverse kidney events
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90 days
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Spolupracovníci a vyšetřovatelé
Sponzor
Spolupracovníci
Vyšetřovatelé
- Studijní židle: Melanie Meersch, University hospital Muenster
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia
Primární dokončení (Očekávaný)
Dokončení studie (Očekávaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Odhad)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- 04-AnIt-16
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
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