Clinical trial NCT02997748: Remote Ischemic Preconditioning After Cardiac Surgery
Official title: Remote Ischemic Preconditioning to Prevent Acute Kidney Injury in High Risk Patients After Cardiac Surgery (RIPCRenal)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Cardiac Surgery, Aortocoronary Bypass
Keywords: acute kidney injury
cardiac surgery
Remote ischemic preconditioning
[TIMP-2]*[IGFBP7]
Lead sponsor: University Hospital Muenster
Sponsor class: OTHER
Collaborators: name: Else Kröner Fresenius Foundation
First posted: 2016-12-20
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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)?

Eligibility criteria: 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

Primary outcomes:
measure: Change in urinary [TIMP-2]*[IGFBP7]
timeFrame: within 12 hours after CPB
Secondary outcomes:
measure: AKI within 72 hours
timeFrame: 72 h
measure: Dialysis within 7 days of surgery
timeFrame: 7 days
measure: All-cause-mortality at 90 days
timeFrame: 90 d
measure: Dialysis at day 90
timeFrame: 90 days
measure: Renal recovery at day 90
timeFrame: 90 days
measure: MAKE 90
timeFrame: 90 days
Other outcomes:
Locations:
city: Muenster
country: Germany
facility: University Hospital Muenster
Study officials:
affiliation: University Hospital Muenster
name: Melanie Meersch
role: STUDY_CHAIR
References: