Remote Ischemic Preconditioning After Cardiac Surgery (RIPCRenal)

University Hospital Muenster

Status: Unknown

Conditions: Cardiac Surgery, Aortocoronary Bypass

Treatments: Procedure: Remote ischemic preconditioning (RIPC)

Study type: Interventional

Funder types: Other

Identifiers

NCT02997748

04-AnIt-16

Details and patient eligibility

About

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.

Full 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)?

Enrollment: 180 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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180 participants in 6 patient groups

Observational group

No Intervention group

Description:

No intervention, standard care

Sham RIPC

Sham Comparator group

Description:

Three cycles of 5- min upper limb sham ischemia

Treatment:

Procedure: Remote ischemic preconditioning (RIPC)

RIPC-Group 1

Experimental group

Description:

Three cycles of 5- min upper limb ischemia

Treatment:

Procedure: Remote ischemic preconditioning (RIPC)

RIPC-Group 2

Experimental group

Description:

Three cycles of 7-min upper limb ischemia

Treatment:

Procedure: Remote ischemic preconditioning (RIPC)

RIPC-Group 3

Experimental group

Description:

Three cycles of 10-min upper limb ischemia

Treatment:

Procedure: Remote ischemic preconditioning (RIPC)

RIPC-Group 4

Experimental group

Description:

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

Treatment:

Procedure: Remote ischemic preconditioning (RIPC)