Remote Ischemic Preconditioning After Cardiac Surgery (RIPCRenal)
Remote Ischemic Preconditioning to Prevent Acute Kidney Injury in High Risk Patients After Cardiac Surgery (RIPCRenal)
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
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)?
Undersøgelsestype
Tilmelding (Forventet)
Fase
- Ikke anvendelig
Kontakter og lokationer
Studiesteder
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Muenster, Tyskland, D-48149
- Rekruttering
- University hospital Muenster
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Kontakt:
- Alexander Zarbock, PhD, MD
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Tredobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Ingen indgriben: Observational group
No intervention, standard care
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Sham-komparator: 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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Eksperimentel: 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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Eksperimentel: 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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Eksperimentel: 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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Eksperimentel: 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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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Change in urinary [TIMP-2]*[IGFBP7]
Tidsramme: 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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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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AKI within 72 hours
Tidsramme: 72 h
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72 h
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Dialysis within 7 days of surgery
Tidsramme: 7 days
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7 days
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All-cause-mortality at 90 days
Tidsramme: 90 d
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90 d
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Dialysis at day 90
Tidsramme: 90 days
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90 days
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Renal recovery at day 90
Tidsramme: 90 days
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90 days
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MAKE 90
Tidsramme: 90 days
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major adverse kidney events
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90 days
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Samarbejdspartnere og efterforskere
Sponsor
Samarbejdspartnere
Efterforskere
- Studiestol: Melanie Meersch, University hospital Muenster
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Forventet)
Studieafslutning (Forventet)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- 04-AnIt-16
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
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Kliniske forsøg med Remote ischemic preconditioning (RIPC)
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Rennes University HospitalAfsluttet