NCT02997748

Remote Ischemic Preconditioning After Cardiac Surgery

Remote Ischemic Preconditioning to Prevent Acute Kidney Injury in High Risk Patients After Cardiac Surgery (RIPCRenal)

• Status: Unknown
• Phase: N/A
• Study type: Interventional
• Enrollment: 180 (estimated)
• Sponsor: University Hospital Muenster · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Acute kidney injury (AKI) is a well-recognized complication after cardiac surgery with cardiopulmonary bypass (CPB). The aim of this study is to reduce the incidence of AKI by implementing remote ischemic preconditioning and to evaluate the dose-response relationship using the biomarkers urinary \[TIMP-2\] \*\[IGFBP7\] in high risk patients undergoing cardiac surgery.

Detailed description

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)?

Conditions

• Cardiac Surgery, Aortocoronary Bypass

Interventions

Type	Name	Description
PROCEDURE	Remote ischemic preconditioning (RIPC)	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.

Timeline

• Start date: 2016-12-01
• Primary completion: 2019-06-01
• Completion: 2019-09-01
• First posted: 2016-12-20
• Last updated: 2018-01-30

Locations

1 site across 1 country: Germany