Remote Ischemic Preconditioning After Cardiac Surgery

Cardiac Surgery, Aortocoronary Bypass Clinical Trial

— RIPCRenal  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02997748
• Other study ID #: 04-AnIt-16
• Status: Recruiting
• Phase: N/A
• First received: December 15, 2016
• Last updated: January 29, 2018
• Start date: December 2016
• Est. completion date: September 2019

Study information

• Verified date: January 2018
• Source: University Hospital Muenster
• Contact: Melanie Meersch, MD
• Phone: +49-251-8347282
• Email: aki[@]anit.uni-muenster.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)?

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: September 2019
• Est. primary completion date: June 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Kidney Injury
• Cardiac Surgery, Aortocoronary Bypass

Intervention

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.

Locations

Country	Name	City	State
Germany	University Hospital Muenster	Muenster

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital Muenster	Else Kröner Fresenius Foundation

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in urinary [TIMP-2]*[IGFBP7]	Biomarkers will be measured at different time points after to evaluate the effect of RIPC on [TIMP-2]*[IGFBP7]	within 12 hours after CPB
Secondary	AKI within 72 hours		72 h
Secondary	Dialysis within 7 days of surgery		7 days
Secondary	All-cause-mortality at 90 days		90 d
Secondary	Dialysis at day 90		90 days
Secondary	Renal recovery at day 90		90 days
Secondary	MAKE 90	major adverse kidney events	90 days